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Sample records for controlling hypoxic sensitivity

  1. Clusterin and chemotherapy sensitivity under normoxic and graded hypoxic conditions in colorectal cancer.

    LENUS (Irish Health Repository)

    Kevans, David

    2012-06-01

    In vitro studies have shown that clusterin modulates treatment sensitivity in a number of human cancers; however, the interaction between clusterin expression and hypoxia in controlling treatment response in CRC has not previously been examined. The aim of this study was to assess the effect of clusterin overexpression in CRC cells on sensitivity to 5-fluorouracil (5-FU), oxaliplatin and FOLFOX treatment under normoxic and graded hypoxic conditions.

  2. LET-painting increases tumour control probability in hypoxic tumours.

    Science.gov (United States)

    Bassler, Niels; Toftegaard, Jakob; Lühr, Armin; Sørensen, Brita Singers; Scifoni, Emanuele; Krämer, Michael; Jäkel, Oliver; Mortensen, Lise Saksø; Overgaard, Jens; Petersen, Jørgen B

    2014-01-01

    LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

  3. Lysyl oxidase mediates hypoxic control of metastasis

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Giaccia, Amato J

    2006-01-01

    Hypoxic cancer cells pose a great challenge to the oncologist because they are especially aggressive, metastatic, and resistant to therapy. Recently, we showed that elevation of the extracellular matrix protein lysyl oxidase (LOX) correlates with metastatic disease and is essential for hypoxia...

  4. Trichromatic and dichromatic relative sensitivity to green light in a mild hypoxic environment.

    Science.gov (United States)

    Hovis, Jeffery K; Milburn, Nelda J; Nesthus, Thomas E

    2013-11-01

    Several studies have reported that individuals with normal color vision have a relative decrease in sensitivity to green light in hypoxic environments approximating altitudes above 4000 m. Because there is little available information describing the effects of mild hypoxic environments (less than 4000 m) in subjects with deficient color-vision, we examined the effect of mild hypoxia on the relative sensitivity to green light for color-normal and color-deficient subjects. Relative sensitivity to the green light was measured using the Medmont C-100 at ground and 3780 m in an altitude chamber. There were 30 subjects, 13 with normal color vision and 17 with a congenital red-green defect, who participated in the study. The relative sensitivity to the green light was determined from the average of four settings measured during the 4.5-h trial. Color-normals and anomalous trichromats showed a small decrease in the relative sensitivity to the green light at 3780 m compared to ground. In contrast to the trichromatic results, the relative sensitivity of the dichromats to the green light did not differ between 3780 m and ground. Our results show that a decrease in the relative sensitivity to green light can occur in hypoxic environments that are equivalent to altitudes greater than 3700 m in individuals with trichromatic but not dichromatic color vision. Although the change in sensitivity was significant, it was small and unlikely to have any operational impact.

  5. Ixr1p and the control of the Saccharomyces cerevisiae hypoxic response.

    Science.gov (United States)

    Vizoso-Vázquez, Angel; Lamas-Maceiras, Mónica; Becerra, Manuel; González-Siso, M Isabel; Rodríguez-Belmonte, Esther; Cerdán, M Esperanza

    2012-04-01

    In Saccharomyces cerevisiae, adaptation to hypoxia/anaerobiosis requires the transcriptional induction or derepression of multiple genes organized in regulons controlled by specific transcriptional regulators. Ixr1p is a transcriptional regulatory factor that causes aerobic repression of several hypoxic genes (COX5B, TIR1, and HEM13) and also the activation of HEM13 during hypoxic growth. Analysis of the transcriptome of the wild-type strain BY4741 and its isogenic derivative Δixr1, grown in aerobic and hypoxic conditions, reveals differential regulation of genes related not only to the hypoxic and oxidative stress responses but also to the re-adaptation of catabolic and anabolic fluxes in response to oxygen limitation. The function of Ixr1p in the transcriptional regulation of genes from the sulfate assimilation pathway and other pathways producing α-keto acids is of biotechnological importance for industries based on yeast-derived fermentation products.

  6. Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA Damaging Agents

    Science.gov (United States)

    Vasilevskaya, Irina A.; Selvakumaran, Muthu; Hierro, Lucia Cabal; Goldstein, Sara R.; Winkler, Jeffrey D.; O'Dwyer, Peter J.

    2015-01-01

    Purpose We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs. Experimental design In a panel of cell lines we investigated effects of pharmacological and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38 and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo. Results Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, though synergy is not always hypoxia-specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (non-responsive) lines. In HT29 and SW620 cells CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, where tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy. Conclusions These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic. PMID:26023085

  7. Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

    Science.gov (United States)

    Gelfand, R.; Lambertsen, C. J.; Clark, J. M.; Hopkin, E.

    1998-01-01

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

  8. EVALUATION OF THE CLINICAL USE OF HYPOXIC CELL SENSITIZERS IN RADIATION THERAPY OF MALIGNANT EPITHELIAL SKIN TUMORS

    Directory of Open Access Journals (Sweden)

    P. Yu. Polyakov

    2015-01-01

    Full Text Available Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells.Materials and methods: The study was performed in 517 patients with basal cell (n = 361 and squamous cell (n = 156 skin cancer, 274 (53% of whom had T2 and 243 (47%, T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm². The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05. In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was

  9. Selective Intracellular Delivery of Recombinant Arginine Deiminase (ADI) Using pH-Sensitive Cell Penetrating Peptides To Overcome ADI Resistance in Hypoxic Breast Cancer Cells.

    Science.gov (United States)

    Yeh, Tzyy-Harn; Chen, Yun-Ru; Chen, Szu-Ying; Shen, Wei-Chiang; Ann, David K; Zaro, Jennica L; Shen, Li-Jiuan

    2016-01-04

    Arginine depletion strategies, such as pegylated recombinant arginine deiminase (ADI-PEG20), offer a promising anticancer treatment. Many tumor cells have suppressed expression of a key enzyme, argininosuccinate synthetase 1 (ASS1), which converts citrulline to arginine. These tumor cells become arginine auxotrophic, as they can no longer synthesize endogenous arginine intracellularly from citrulline, and are therefore sensitive to arginine depletion therapy. However, since ADI-PEG20 only depletes extracellular arginine due to low internalization, ASS1-expressing cells are not susceptible to treatment since they can synthesize arginine intracellularly. Recent studies have found that several factors influence ASS1 expression. In this study, we evaluated the effect of hypoxia, frequently encountered in many solid tumors, on ASS1 expression and its relationship to ADI-resistance in human MDA-MB-231 breast cancer cells. It was found that MDA-MB-231 cells developed ADI resistance in hypoxic conditions with increased ASS1 expression. To restore ADI sensitivity as well as achieve tumor-selective delivery under hypoxia, we constructed a pH-sensitive cell penetrating peptide (CPP)-based delivery system to carry ADI inside cells to deplete both intra- and extracellular arginine. The delivery system was designed to activate the CPP-mediated internalization only at the mildly acidic pH (6.5-7) associated with the microenvironment of hypoxic tumors, thus achieving better selectivity toward tumor cells. The pH sensitivity of the CPP HBHAc was controlled by recombinant fusion to a histidine-glutamine (HE) oligopeptide, generating HBHAc-HE-ADI. The tumor distribution of HBHAc-HE-ADI was comparable to ADI-PEG20 in a mouse xenograft model of human breast cancer cells in vivo. In addition, HBHAc-HE-ADI showed increased in vitro cellular uptake in cells incubated in a mildly acidic pH (hypoxic conditions) compared to normal pH (normoxic conditions), which correlated with pH-sensitive

  10. Sanazole as a sensitizer of hypoxic cells with radical radiation in the treatment of advanced cancer of cervix an Indian experience.

    Science.gov (United States)

    Huilgol, Nagraj G; Dobrowsky, Werner; Tatsuzaki, Hideo; Chatterjee, Neela A; Kagiya, V T; Das, Kaushik

    2002-06-01

    AK-2123, is a nitrotriazole with a potential to sensitize hypoxic tissue to radiation. Cancer of cervix in advanced stages are predominantly treated with radiation. These are the tumours which harbour a large hypoxic core. This is an Indian experience of the multicentric trial. Patients were randomized to control and AK-2123 arm. 49 patients were randomized to each group. Patients received external radiation with telecobalt to a dose of 50 Gy in five weeks. Those in the study arm received 600 mg/m2, on alternate days. The patients were further treated with intracavitory radiation a dose of 20 Gy. The total dose of 70 Gy was achieved. Patients in the study arm had a complete response of 71.43% (35 of 49) while only 21 of 49 (42.86%) responded in the control group. The overall survival at two years was 72.2% for the study group and 32.43% for control. Neuropathy, a drug related toxicity was transient except, in one patient, which has persisted. AK-2123, has shown significant radiation sensitizing potential.

  11. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders.

  12. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    Directory of Open Access Journals (Sweden)

    Ostergaard L

    2014-09-01

    ultimately survived. Their systemic blood pressure fell with acute (5 minutes hypoxia but was partially recovered over time. In contrast, right ventricular pressures increased with acute (5 minutes hypoxia and normalized after 16 hours. No signs of pulmonary inflammation or edema were found despite prolonged hypoxia. Whereas copeptin levels increased significantly after acute (5 minutes hypoxia and then returned to near baseline after 16 hours, mid-regional proANP levels were even further increased after 16 hours of exposure to hypoxia. Conclusion: Plasma copeptin is a sensitive marker of acute (5 minutes exposure to severe hypoxia, and subsequent regulation can indicate recovery. Copeptin levels can therefore reflect clinical and physiological changes in response to hypoxia and indicate recovery from ongoing hypoxic exposure. Keywords: vasoactive peptides, hypoxia, copeptin, atrial natriuretic peptide, acclimatization, adaptation, critical illness

  13. Hypoxic radiosensitization: adored and ignored.

    Science.gov (United States)

    Overgaard, Jens

    2007-09-10

    Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new imaging and physiologic techniques, and a substantial amount of data indicates the presence of hypoxia in many types of human tumors, although with a considerable heterogeneity among individual tumors. Controlled clinical trials during the last 40 years have indicated that this source of radiation resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated systematic review identified 10,108 patients in 86 randomized trials designed to modify tumor hypoxia in patients treated with curative attempted primary radiation therapy alone. Overall modification of tumor hypoxia significantly improved the effect of radiotherapy, with an odds ratio of 0.77 (95% CI, 0.71 to 0.86) for the outcome of locoregional control and with an associated significant overall survival benefit (odds ratio = 0.87; 95% CI, 0.80 to 0.95). No significant influence was found on the incidence of distant metastases or on the risk of radiation-related complications. Ample data exist to support a high level of evidence for the benefit of hypoxic modification. However, hypoxic modification still has no impact on general clinical practice.

  14. Hypoxic radiosensitization: adored and ignored

    DEFF Research Database (Denmark)

    Overgaard, Jens

    2007-01-01

    resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated...

  15. Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon

    Institute of Scientific and Technical Information of China (English)

    Yu JIN; Wei-ping XIE; Hong WANG

    2012-01-01

    Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries.The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance,reverse pulmonary vascular remodeling,and thereby improving right ventricular function.Iptakalim,a lipophilic para-amino compound with a low molecular weight,has been demonstrated to be a new selective ATP-sensitive potassium (KATP) channel opener via pharmacological,electrophysiological,biochemical studies,and receptor binding tests.In hypoxia-induced animal models,iptakalim decreases the elevated mean pressure in pulmonary arteries,and attenuates remodeling in the right ventricle,pulmonary arteries and airways.Furthermore,iptakalim has selective antihypertensive effects,selective vasorelaxation effects on smaller arteries,and protective effects on endothelial cells,but no effects on the central nervous,respiratory,digestive or endocrine systems at therapeutic dose.Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1,reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells.Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials,it can be a potential candidate of HPH in the future.

  16. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  17. Targeting the tumour vasculature: exploitation of low oxygenation and sensitivity to NOS inhibition by treatment with a hypoxic cytotoxin.

    Science.gov (United States)

    Baker, Jennifer H E; Kyle, Alastair H; Bartels, Kirsten L; Methot, Stephen P; Flanagan, Erin J; Balbirnie, Andrew; Cran, Jordan D; Minchinton, Andrew I

    2013-01-01

    Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels.

  18. Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.

    Science.gov (United States)

    Yang, Dianer; Sun, Yu-Yo; Bhaumik, Siddhartha Kumar; Li, Yikun; Baumann, Jessica M; Lin, Xiaoyi; Zhang, Yujin; Lin, Shang-Hsuan; Dunn, R Scott; Liu, Chia-Yang; Shie, Feng-Shiun; Lee, Yi-Hsuan; Wills-Karp, Marsha; Chougnet, Claire A; Kallapur, Suhas G; Lewkowich, Ian P; Lindquist, Diana M; Murali-Krishna, Kaja; Kuan, Chia-Yi

    2014-12-03

    Intrauterine infection (chorioamnionitis) aggravates neonatal hypoxic-ischemic (HI) brain injury, but the mechanisms linking systemic inflammation to the CNS damage remain uncertain. Here we report evidence for brain influx of T-helper 17 (TH17)-like lymphocytes to coordinate neuroinflammatory responses in lipopolysaccharide (LPS)-sensitized HI injury in neonates. We found that both infants with histological chorioamnionitis and rat pups challenged by LPS/HI have elevated expression of the interleukin-23 (IL-23) receptor, a marker of early TH17 lymphocytes, in the peripheral blood mononuclear cells. Post-LPS/HI administration of FTY720 (fingolimod), a sphingosine-1-phosphate receptor agonist that blocks lymphocyte trafficking, mitigated the influx of leukocytes through the choroid plexus and acute induction of nuclear factor-κB signaling in the brain. Subsequently, the FTY720 treatment led to attenuated blood-brain barrier damage, fewer cluster of differentiation 4-positive, IL-17A-positive T-cells in the brain, less proinflammatory cytokine, and better preservation of growth and white matter functions. The FTY720 treatment also provided dose-dependent reduction of brain atrophy, rescuing >90% of LPS/HI-induced brain tissue loss. Interestingly, FTY720 neither opposed pure-HI brain injury nor directly inhibited microglia in both in vivo and in vitro models, highlighting its unique mechanism against inflammation-sensitized HI injury. Together, these results suggest that the dual hit of systemic inflammation and neonatal HI injury triggers early onset of the TH17/IL-17-mediated immunity, which causes severe brain destruction but responds remarkably to the therapeutic blockade of lymphocyte trafficking.

  19. Cable Bacteria Control Iron-Phosphorus Dynamics in Sediments of a Coastal Hypoxic Basin.

    Science.gov (United States)

    Sulu-Gambari, Fatimah; Seitaj, Dorina; Meysman, Filip J R; Schauer, Regina; Polerecky, Lubos; Slomp, Caroline P

    2016-02-01

    Phosphorus is an essential nutrient for life. The release of phosphorus from sediments is critical in sustaining phytoplankton growth in many aquatic systems and is pivotal to eutrophication and the development of bottom water hypoxia. Conventionally, sediment phosphorus release is thought to be controlled by changes in iron oxide reduction driven by variations in external environmental factors, such as organic matter input and bottom water oxygen. Here, we show that internal shifts in microbial communities, and specifically the population dynamics of cable bacteria, can also induce strong seasonality in sedimentary iron-phosphorus dynamics. Field observations in a seasonally hypoxic coastal basin demonstrate that the long-range electrogenic metabolism of cable bacteria leads to a dissolution of iron sulfides in winter and spring. Subsequent oxidation of the mobilized ferrous iron with manganese oxides results in a large stock of iron-oxide-bound phosphorus below the oxic zone. In summer, when bottom water hypoxia develops and cable bacteria are undetectable, the phosphorus associated with these iron oxides is released, strongly increasing phosphorus availability in the water column. Future research should elucidate whether formation of iron-oxide-bound phosphorus driven by cable bacteria, as observed in this study, contributes to the seasonality in iron-phosphorus cycling in aquatic sediments worldwide.

  20. Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

    Science.gov (United States)

    Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

    1998-06-01

    Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain

  1. Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Moisés Pérez; Carmen García-Limones; Inés Zapico; Anabel Marina; M. Lienhard Schmitz; Eduardo Mu(n)oz; Marco A. Calzado

    2012-01-01

    The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3,which in turn increases the stability of hypoxia-inducible factor (HIF)-1α.In the present study,we identify the serine/threonine kinase DYRK2 as SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16,Thr26,Ser28,Ser68,and Thr119).Phosphomimetic and phospho-mutant forms of SIAH2 exhibit different subcellular localizations and consequently change in PHD3 degrading activity.Accordingly,phosphorylated SIAH2 is more active than the wild-type E3 ligase and shows an increased ability to trigger the HIF-1α-mediated transcriptional response and angiogenesis.We also found that SIAH2 knockdown increases DYRK2 stability,whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation.Hypoxic conditions cause a SIAH2-dependent DYRK2 polyubiquitination and degradation which ultimately also results in an impaired SIAH2 phosphorylation.Similarly,DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions,suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors.

  2. Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways.

    Science.gov (United States)

    Pérez, Moisés; García-Limones, Carmen; Zapico, Inés; Marina, Anabel; Schmitz, M Lienhard; Muñoz, Eduardo; Calzado, Marco A

    2012-10-01

    The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3, which in turn increases the stability of hypoxia-inducible factor (HIF)-1α. In the present study, we identify the serine/threonine kinase DYRK2 as SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119). Phosphomimetic and phospho-mutant forms of SIAH2 exhibit different subcellular localizations and consequently change in PHD3 degrading activity. Accordingly, phosphorylated SIAH2 is more active than the wild-type E3 ligase and shows an increased ability to trigger the HIF-1α-mediated transcriptional response and angiogenesis. We also found that SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation. Hypoxic conditions cause a SIAH2-dependent DYRK2 polyubiquitination and degradation which ultimately also results in an impaired SIAH2 phosphorylation. Similarly, DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors.

  3. Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Stenmark, Kurt R; Tuder, Rubin M; El Kasmi, Karim C

    2015-11-15

    Pulmonary hypertension (PH) is a complex, multifactorial syndrome that remains poorly understood despite decades of research. PH is characterized by profound pulmonary artery (PA) remodeling that includes significant fibro-proliferative and inflammatory changes of the PA adventitia. In line with the emerging concept that PH shares key features with cancer, recent work centers on the idea that PH results from a multistep process driven by reprogramming of gene-expression patterns that govern changes in cell metabolism, inflammation, and proliferation. Data demonstrate that in addition to PA endothelial cells and smooth muscle cells, adventitial fibroblasts from animals with experimental hypoxic PH and from humans with PH (hereafter, termed PH-Fibs) exhibit proinflammatory activation, increased proliferation, and apoptosis resistance, all in the context of metabolic reprogramming to aerobic glycolysis. PH-Fibs can also recruit, retain, and activate naïve macrophages (Mϕ) toward a proinflammatory/proremodeling phenotype through secretion of chemokines, cytokines, and glycolytic metabolites, among which IL-6 and lactate play key roles. Furthermore, these fibroblast-activated Mϕ (hereafter, termed FAMϕ) exhibit aerobic glycolysis together with high expression of arginase 1, Vegfa, and I1lb, all of which require hypoxia-inducible factor 1α and STAT3 signaling. Strikingly, in situ, the adventitial Mϕ phenotype in the remodeled PA closely resembles the Mϕ phenotype induced by fibroblasts in vitro (FAMϕ), suggesting that FAMϕ crosstalk involving metabolic and inflammatory signals is a critical, pathogenetic component of vascular remodeling. This review discusses metabolic and inflammatory changes in fibroblasts and Mϕ in PH with the goal of raising ideas about new interventions to abrogate remodeling in hypoxic forms of PH.

  4. Mitochondrial ATP-sensitive potassium channel activity and hypoxic preconditioning are independent of an inwardly rectifying potassium channel subunit in Caenorhabditis elegans.

    Science.gov (United States)

    Wojtovich, Andrew P; DiStefano, Peter; Sherman, Teresa; Brookes, Paul S; Nehrke, Keith

    2012-02-17

    Hypoxic preconditioning (HP) is an evolutionarily-conserved mechanism that protects an organism against stress. The mitochondrial ATP-sensitive K(+) channel (mK(ATP)) plays an essential role in the protective signaling, but remains molecularly undefined. Several lines of evidence suggest that mK(ATP) may arise from an inward rectifying K(+) channel (Kir). The genetic model organism Caenorhabditis elegans exhibits HP and displays mK(ATP) activity. Here, we investigate the tissue expression profile of the three C. elegans Kir genes and demonstrate that mutant strains where the irk genes have been deleted either individually or in combination can be protected by HP and exhibit robust mK(ATP) channel activity in purified mitochondria. These data suggest that the mK(ATP) in C. elegans does not arise from a Kir derived channel.

  5. Mitochondrial ATP-sensitive potassium channel activity and hypoxic preconditioning are independent of an inwardly rectifying potassium channel subunit in C. elegans

    Science.gov (United States)

    Wojtovich, Andrew P.; DiStefano, Peter; Sherman, Teresa; Brookes, Paul S.; Nehrke, Keith

    2012-01-01

    Hypoxic preconditioning (HP) is an evolutionarily-conserved mechanism that protects an organism against stress. The mitochondrial ATP-sensitive K+ channel (mKATP) plays an essential role in the protective signaling, but remains molecularly undefined. Several lines of evidence suggest that mKATP may arise from an inward rectifying K+ channel (Kir). The genetic model organism C. elegans exhibits HP and displays mKATP activity. Here, we investigate the tissue expression profile of the three C. elegans Kir genes and demonstrate that mutant strains where the irk genes have been deleted either individually or in combination can be protected by HP and exhibit robust mKATP channel activity in purified mitochondria. These data suggest that the mKATP in C. elegans does not arise from a Kir derived channel. PMID:22281198

  6. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    DEFF Research Database (Denmark)

    Hedegaard, Elise Røge; Stankevicius, Edgaras; Simonsen, Ulf

    2011-01-01

    of large coronary arteries. RESULTS: In prostaglandin F2α (PGF2α, 10 μM)-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except...... at 1% O2. The endothelin receptor antagonist SB217242 (10 μM) markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic...... arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine) reduced hypoxic vasodilation. NO-induced vasodilation...

  7. Cable Bacteria Control Iron−Phosphorus Dynamics in Sediments of a Coastal Hypoxic Basin

    NARCIS (Netherlands)

    Sulu-Gambari, F; Seitaj, D.; Meysman, F.; Schauer, R.; Polerecky, L.; Slomp, C.P.

    2016-01-01

    Phosphorus is an essential nutrient for life. The release ofphosphorus from sediments is critical in sustaining phytoplankton growthin many aquatic systems and is pivotal to eutrophication and thedevelopment of bottom water hypoxia. Conventionally, sedimentphosphorus release is thought to be control

  8. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  9. Cable Bacteria Control Iron−Phosphorus Dynamics in Sediments of a Coastal Hypoxic Basin

    OpenAIRE

    Sulu-Gambari, F; Seitaj, D.; F. Meysman; Schauer, R.; Polerecky, L.; Slomp, C. P.

    2016-01-01

    Phosphorus is an essential nutrient for life. The release ofphosphorus from sediments is critical in sustaining phytoplankton growthin many aquatic systems and is pivotal to eutrophication and thedevelopment of bottom water hypoxia. Conventionally, sedimentphosphorus release is thought to be controlled by changes in iron oxidereduction driven by variations in external environmental factors, such asorganic matter input and bottom water oxygen. Here, we show thatinternal shifts in microbial com...

  10. Oxygen-Sensitive Calcium Channels in Vascular Smooth Muscle and Their Possible Role in Hypoxic Arterial Relaxation

    Science.gov (United States)

    Franco-Obregon, A.; Urena, J.; Lopez-Barneo, J.

    1995-05-01

    We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O_2 tension (PO_2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca2+ whose frequency depends on extracellular Ca2+ influx. Switching from a PO_2 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2+ oscillations. In voltage-clamped cells, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low PO_2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low PO_2 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of O_2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.

  11. Hypoxic regulation of hand1 controls the fetal-neonatal switch in cardiac metabolism.

    Directory of Open Access Journals (Sweden)

    Ross A Breckenridge

    2013-09-01

    Full Text Available Cardiomyocytes are vulnerable to hypoxia in the adult, but adapted to hypoxia in utero. Current understanding of endogenous cardiac oxygen sensing pathways is limited. Myocardial oxygen consumption is determined by regulation of energy metabolism, which shifts from glycolysis to lipid oxidation soon after birth, and is reversed in failing adult hearts, accompanying re-expression of several "fetal" genes whose role in disease phenotypes remains unknown. Here we show that hypoxia-controlled expression of the transcription factor Hand1 determines oxygen consumption by inhibition of lipid metabolism in the fetal and adult cardiomyocyte, leading to downregulation of mitochondrial energy generation. Hand1 is under direct transcriptional control by HIF1α. Transgenic mice prolonging cardiac Hand1 expression die immediately following birth, failing to activate the neonatal lipid metabolising gene expression programme. Deletion of Hand1 in embryonic cardiomyocytes results in premature expression of these genes. Using metabolic flux analysis, we show that Hand1 expression controls cardiomyocyte oxygen consumption by direct transcriptional repression of lipid metabolising genes. This leads, in turn, to increased production of lactate from glucose, decreased lipid oxidation, reduced inner mitochondrial membrane potential, and mitochondrial ATP generation. We found that this pathway is active in adult cardiomyocytes. Up-regulation of Hand1 is protective in a mouse model of myocardial ischaemia. We propose that Hand1 is part of a novel regulatory pathway linking cardiac oxygen levels with oxygen consumption. Understanding hypoxia adaptation in the fetal heart may allow development of strategies to protect cardiomyocytes vulnerable to ischaemia, for example during cardiac ischaemia or surgery.

  12. Risk-sensitivity in sensorimotor control

    Directory of Open Access Journals (Sweden)

    Daniel A. Braun

    2011-01-01

    Full Text Available Recent advances in theoretical neuroscience suggest that motor control can be considered as a continuous decision-making process in which uncertainty plays a key role. Decision-makers can be risk-sensitive with respect to this uncertainty in that they may not only consider the average payoff of an outcome, but also consider the variability of the payoffs. Although such risk-sensitivity is a well-established phenomenon in psychology and economics, it has been much less studied in motor control. In fact, leading theories of motor control, such as optimal feedback control, assume that motor behaviors can be explained as the optimization of a given expected payoff or cost. Here we review evidence that humans exhibit risk-sensitivity in their motor behaviors, thereby demonstrating sensitivity to the variability of ‘motor costs’. Furthermore, we discuss how risk-sensitivity can be incorporated into optimal feedback control models of motor control. We conclude that risk-sensitivity is an important concept in understanding individual motor behavior under uncertainty.

  13. Preterm Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Krishna G Gopagondanahalli

    2016-10-01

    Full Text Available Hypoxic ischemic encephalopathy (HIE is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic ischemic episode before or during birth. However, in the preterm infant, defining hypoxic ischemic injury, its clinical course, monitoring and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic ischemic insult in preterm infants is probably higher than recognized, and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies.

  14. Hypoxic radiosensitizers: substituted styryl derivatives.

    Science.gov (United States)

    Nudelman, A; Falb, E; Odesa, Y; Shmueli-Broide, N

    1994-10-01

    A number of novel styryl epoxides, N-substituted-styryl-ethanolamines, N-mono and N,N'-bis-(2-hydroxyethyl)-cinnamamides--analogues to the known radiosensitizers RSU-1069, pimonidazole and etanidazole--display selective hypoxic radiosensitizing activity. The styryl group, especially when substituted by electron withdrawing groups, was found to be bioisosteric to the nitroimidazolyl functionality. The most active derivative 2-(2'-nitrophenyl)ethen-1-yl-oxirane 8a displayed a sensitizer enhancement ratio (SER) of 5 relative to misonidazole.

  15. Keynote address: cellular reduction of nitroimidazole drugs: potential for selective chemotherapy and diagnosis of hypoxic cells

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, J.D.; Lee, J.; Meeker, B.E.

    1989-04-01

    Nitroimidazole drugs were initially developed as selective radiosensitizers of hypoxic cells and, consequently, as adjuvants to improve the local control probabilities of current radiotherapies. Misonidazole (MISO), the prototype radiosensitizing drug, was found in Phase I clinical studies to cause dose-limiting neurotoxicities (mainly peripheral neuropathies). MISO was also found to be cytotoxic in the absence of radiation and to covalently bind to cellular molecules, both processes demonstrating rates much higher in hypoxic compared with oxygenated cells. It is likely that neurotoxicity, cellular cytotoxicity and adduct formation results from reactions between reduction intermediates of MISO and cellular target molecules. Spin-offs from radiosensitizer research include the synthesis and characterization of more potent hypoxic cytotoxins and the exploitation of sensitizer-adducts as probes for measuring cellular and tissue oxygen levels. Current developments in hypoxic cell cytotoxin and hypoxic cell marker research are reviewed with specific examples from studies which characterize the cellular reduction of TF-MISO, (1-(2-nitro-1-imidazolyl)-3(2,2,2-trifluoroethoxy)-2-propanol). 45 references.

  16. Effect of Intermittent Hypoxic Exposure on Insulin Sensitivity of Obese Rats%间歇低氧暴露对高脂膳食大鼠胰岛素敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    潘哲浩; 翁锡全; 朱宪锋; 沈财利

    2012-01-01

    Objective To explore the effect of intermittent hypoxic exposure on the insulin sensitivity of obese rats induced by high-fat diet. Methods Forty male SD rats were randomly divided into normal diet(fed with standard chow)+ normoxic group,normal diet + intermittent hypoxic exposure group,high-fat diet (fed with high-fat diet)+ normoxic group and high-fat diet + intermittent hypoxic expose group. Rats in intermittent hypoxic groups were exposed in hypoxic atmospheric(15.4% oxygen), l0hrs/day. After 6 weeks intervention,visceral fat volume and serum FBG and FINS were tested,and insulin sensitivity index was calculated. Results As compared with normal diet + normoxic group,visceral fat amount, serum insulin level in high—fat diet + normoxic group decreased significantly (P < 0.01) ,Lee index and visceral fat volume decreased significantly (P < 0.05 ,P < 0.01) ,and insulin sensitivity index increased significantly (P< 0.05 )in normal diet + intermittent hypoxic exposure group. As compared with high—fat diet + normoxic group,Lee index,visceral fat volume and serum insulin level decreased significantly(P < 0.01),insulin sensitivity index increased significantly (P < 0.01 )in high-fat diet + intermittent hypoxic exposure group. Analysis showed that there were positive correlation between visceral fat volume and in-sulin level,and negative correlation between insulin level and insulin sensitivity index(P< 0.01). Conclusion Increase in visceral fat induces elevation of serum insulin level,and reduces insulin sensitivity, while intermittent hypoxia exposure reduces visceral fat content and increases insulin sensitivity%探讨间歇低氧暴露对高脂膳食肥胖大鼠胰岛素抵抗的影响.方法:40只雄性SD大鼠随机分为普通膳食常氧组、普通膳食间歇低氧组、高脂膳食常氧组、高脂膳食间歇低氧组.普通膳食采用普通饲料,高脂膳食采用高脂饲料,间歇低氧暴露采用常压低氧方法,氧浓度控制在15

  17. Cysteine residues 244 and 458-459 within the catalytic subunit of Na,K-ATPase control the enzyme's hydrolytic and signaling function under hypoxic conditions.

    Science.gov (United States)

    Petrushanko, Irina Yu; Mitkevich, Vladimir A; Lakunina, Valentina A; Anashkina, Anastasia A; Spirin, Pavel V; Rubtsov, Peter M; Prassolov, Vladimir S; Bogdanov, Nikolay B; Hänggi, Pascal; Fuller, William; Makarov, Alexander A; Bogdanova, Anna

    2017-10-01

    Our previous findings suggested that reversible thiol modifications of cysteine residues within the actuator (AD) and nucleotide binding domain (NBD) of the Na,K-ATPase may represent a powerful regulatory mechanism conveying redox- and oxygen-sensitivity of this multifunctional enzyme. S-glutathionylation of Cys244 in the AD and Cys 454-458-459 in the NBD inhibited the enzyme and protected cysteines' thiol groups from irreversible oxidation under hypoxic conditions. In this study mutagenesis approach was used to assess the role these cysteines play in regulation of the Na,K-ATPase hydrolytic and signaling functions. Several constructs of mouse α1 subunit of the Na,K-ATPase were produced in which Cys244, Cys 454-458-459 or Cys 244-454-458-459 were replaced by alanine. These constructs were expressed in human HEK293 cells. Non-transfected cells and those expressing murine α1 subunit were exposed to hypoxia or treated with oxidized glutathione (GSSG). Both conditions induced inhibition of the wild type Na,K-ATPase. Enzymes containing mutated mouse α1 lacking Cys244 or all four cysteines (Cys 244-454-458-459) were insensitive to hypoxia. Inhibitory effect of GSSG was observed for wild type murine Na,K-ATPase, but was less pronounced in Cys454-458-459Ala mutant and completely absent in the Cys244Ala and Cys 244-454-458-459Ala mutants. In cells, expressing wild type enzyme, ouabain induced activation of Src and Erk kinases under normoxic conditions, whereas under hypoxic conditions this effect was inversed. Cys454-458-459Ala substitution abolished Src kinase activation in response to ouabain treatment, uncoupled Src from Erk signaling, and interfered with O2-sensitivity of Na,K-ATPase signaling function. Moreover, modeling predicted that S-glutathionylation of Cys 458 and 459 should prevent inhibitory binding of Src to NBD. Our data indicate for the first time that cysteine residues within the AD and NBD influence hydrolytic as well as receptor function of the Na

  18. Cysteine residues 244 and 458–459 within the catalytic subunit of Na,K-ATPase control the enzyme's hydrolytic and signaling function under hypoxic conditions

    Directory of Open Access Journals (Sweden)

    Irina Yu. Petrushanko

    2017-10-01

    Full Text Available Our previous findings suggested that reversible thiol modifications of cysteine residues within the actuator (AD and nucleotide binding domain (NBD of the Na,K-ATPase may represent a powerful regulatory mechanism conveying redox- and oxygen-sensitivity of this multifunctional enzyme. S-glutathionylation of Cys244 in the AD and Cys 454-458-459 in the NBD inhibited the enzyme and protected cysteines’ thiol groups from irreversible oxidation under hypoxic conditions. In this study mutagenesis approach was used to assess the role these cysteines play in regulation of the Na,K-ATPase hydrolytic and signaling functions. Several constructs of mouse α1 subunit of the Na,K-ATPase were produced in which Cys244, Cys 454-458-459 or Cys 244-454-458-459 were replaced by alanine. These constructs were expressed in human HEK293 cells. Non-transfected cells and those expressing murine α1 subunit were exposed to hypoxia or treated with oxidized glutathione (GSSG. Both conditions induced inhibition of the wild type Na,K-ATPase. Enzymes containing mutated mouse α1 lacking Cys244 or all four cysteines (Cys 244-454-458-459 were insensitive to hypoxia. Inhibitory effect of GSSG was observed for wild type murine Na,K-ATPase, but was less pronounced in Cys454-458-459Ala mutant and completely absent in the Cys244Ala and Cys 244-454-458-459Ala mutants. In cells, expressing wild type enzyme, ouabain induced activation of Src and Erk kinases under normoxic conditions, whereas under hypoxic conditions this effect was inversed. Cys454-458-459Ala substitution abolished Src kinase activation in response to ouabain treatment, uncoupled Src from Erk signaling, and interfered with O2-sensitivity of Na,K-ATPase signaling function. Moreover, modeling predicted that S-glutathionylation of Cys 458 and 459 should prevent inhibitory binding of Src to NBD. Our data indicate for the first time that cysteine residues within the AD and NBD influence hydrolytic as well as receptor

  19. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  20. Palmitoylation of Gαq determines its association with the thromboxane receptor in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Sikarwar, Anuraq S; Hinton, Martha; Santhosh, K Thomas; Chelikani, Prashen; Dakshinamurti, Shyamala

    2014-01-01

    Pulmonary arterial vasoconstriction is a hallmark of persistent pulmonary hypertension of the newborn (PPHN). We reported increased calcium responses to thromboxane and selectively increased thromboxane prostanoid (TP) association with Gαq in hypoxic pulmonary artery. Palmitoylation of Gαq is important for efficient receptor-Gαq-phospholipase-C interactions. TPα receptor is not itself amenable to palmitoylation. We studied the role of Gαq palmitoylation in constriction of hypoxic pulmonary artery using pharmacological palmitoylation inhibition, the effects of hypoxia on palmitoylation, and the effects of site-specific cysteine substitution mutations of Gαq on Gαq membrane targeting, TPα association, and calcium dose-response curve to a TP agonist. PPHN pulmonary artery and HEK293T cells expressing TPα were exposed to irreversible palmitoylation inhibitor 2-bromopalmitate before challenge with TP agonist U46619. Palmitate uptake was studied in hypoxic and normoxic myocytes. Wild-type Gαq and Gαq cysteine-to-alanine mutants C9A, C10A, and C9A/C10A were transiently coexpressed in HEK293T cells stably expressing TPα. We examined membrane localization of Gαq, TP receptor-Gαq association by coimmunoprecipitation, and Ca(2+) responses to U46619 in hypoxic and normoxic cells. Gαq palmitoylation is essential for the Ca(2+) response to TPα stimulation. Inhibition of palmitoylation reduces contractile force to thromboxane in PPHN but not in control pulmonary artery. Hypoxia increases palmitoylation of Gαq; the hypoxic. but not the normoxic, response to thromboxane is palmitoylation sensitive. Palmitoylation of one N-terminal cysteine is required for physical association of Gαq with the TPα receptor. Palmitoylation of both cysteines is required for Gαq membrane localization and Ca(2+) mobilization. Depalmitoylation of any one Gαq cysteine reduces the hypoxic response to thromboxane challenge to equal that of normoxic cells.

  1. Gene expression changes after hypoxic preconditioning in rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Wei Chen; Jiang-Feng Qiu; Zhi-Qi Zhang; Hai-Feng Luo; Joan Rosello-Catafau; Zhi-Yong Wu

    2006-01-01

    BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic injury, but its mechanism has not been elucidated. The aim of this study was to proifle gene expression patterns involved in hypoxic preconditioning and probable mechanism at the level of gene expression. METHODS: Hepatocytes were divided into 2 groups:control group and hypoxic preconditioning group. Biotin-labeled cRNA from the control group and the hypoxic preconditioning group was hybridized by oligonucleotide microarray. Genes that were signiifcantly associated with hypoxic preconditioning were ifltered, and validated at the level of transcript expression. RESULTS: Forty-three genes with signiifcantly altered expression patterns were discovered and most of them had not been previously reported. Among these genes, genes encoding superoxide dismutase 2 (SOD2)and interleukin 10 (IL-10) in the hypoxic preconditioning group were conifrmed to be up-regulated with real-time quantitative PCR. CONCLUSIONS:Many cytokines are involved in hypoxic preconditioning and protect hepatocytes from hypoxia-reoxygenation injury, and the increase of oxygen free-radical scavengers and anti-inlfammatory factors may play a key role in this phenomenon. Diverse signal pathways are probably involved.

  2. Sensitivity of the Game Control of Ship in Collision Situations

    Directory of Open Access Journals (Sweden)

    Lisowski Józef

    2015-12-01

    Full Text Available The paper introduces the application of the theory of deterministic sensitivity control systems for sensitivity analysis taking place in game control systems of moving objects, such as ships. The sensitivity of parametric model of game ship control process and game control in collision situations - sensitivity to changes in its parameters have been presented. First-order and k-th order sensitivity functions of parametric model of the process and game control are described. The structure of the game ship control system in collision situations and the mathematical model of game control process in the form of state equations are given. Characteristics of sensitivity functions of the model and game ship control process on the base of computer simulation in Matlab/Simulink software have been presented. At the end are given proposals regarding the use of sensitivity analysis to practical synthesis of computer-aided system navigator in potential collision situations.

  3. Understanding Hypoxic Drive and the Release of Hypoxic Vasoconstriction.

    Science.gov (United States)

    Inkrott, Jon C

    2016-01-01

    Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed.

  4. Thalamic mediation of hypoxic respiratory depression in lambs.

    Science.gov (United States)

    Koos, Brian J; Rajaee, Arezoo; Ibe, Basil; Guerra, Catalina; Kruger, Lawrence

    2016-04-01

    Immaturity of respiratory controllers in preterm infants dispose to recurrent apnea and oxygen deprivation. Accompanying reductions in brain oxygen tensions evoke respiratory depression, potentially exacerbating hypoxemia. Central respiratory depression during moderate hypoxia is revealed in the ventilatory decline following initial augmentation. This study determined whether the thalamic parafascicular nuclear (Pf) complex involved in adult nociception and sensorimotor regulation (Bentivoglio M, Balerecia G, Kruger L. Prog Brain Res 87: 53-80, 1991) also becomes a postnatal controller of hypoxic ventilatory decline. Respiratory responses to moderate isocapnic hypoxia were studied in conscious lambs. Hypoxic ventilatory decline was compared with peak augmentation. Pf and/or adjacent thalamic structures were destroyed by the neuron-specific toxin ibotenic acid (IB). IB lesions involving the thalamic Pf abolished hypoxic ventilatory decline. Lesions of adjacent thalamic nuclei that spared Pf and control injections of vehicle failed to blunt hypoxic respiratory depression. Our findings reveal that the thalamic Pf region is a critical controller of hypoxic ventilatory depression and thus a key target for exploring molecular concomitants of forebrain pathways regulating hypoxic ventilatory depression in early development.

  5. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    Directory of Open Access Journals (Sweden)

    Fröbert Ole

    2011-05-01

    Full Text Available Abstract Background The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1 is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA. We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results In prostaglandin F2α (PGF2α, 10 μM-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride(10 μM inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM and the putative NADPH oxidase inhibitor apocynin (10 μM leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene

  6. A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

    Directory of Open Access Journals (Sweden)

    Wu Yonghong

    2010-09-01

    Full Text Available Abstract Background The nematode Caenorhabditis elegans is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in C. elegans, but the changes at the protein level in response to hypoxic stress still remain unclear. Results Here, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in C. elegans. Two-dimensional difference gel electrophoresis (2D-DIGE was used to compare the proteomic maps of wild type C. elegans strain N2 under a 4-h hypoxia treatment (0.2% oxygen and under normoxia (control. A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4, while another three upregulated (ATP-2, ATP-5, VHA-8 were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8 were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11 was further validated by Western blot. In addition, the mutant strain of lev-11(x12 also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings. Conclusions Taken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in C. elegans, and this information will help broaden our knowledge on the mechanism of hypoxia response.

  7. Hypoxic enhancement of exosome release by breast cancer cells

    Directory of Open Access Journals (Sweden)

    King Hamish W

    2012-09-01

    Full Text Available Abstract Background Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Methods Breast cancer cell lines were cultured under either moderate (1% O2 or severe (0.1% O2 hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of  Results Exposure of three different breast cancer cell lines to moderate (1% O2 and severe (0.1% O2 hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. Conclusions These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic

  8. Molecular chaperones and hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Cong Hua

    2017-01-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In

  9. The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

    Institute of Scientific and Technical Information of China (English)

    甄国华; 张珍祥; 徐永健

    2003-01-01

    We investigated the expression of heme oxygenase-1 (HO-l) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin on the expression of HO-1 gene and pulmonary hypertension. A rat model of hypoxic pulmonary hypertension was recreated by exposure to intermittent normobaric hypoxic environment (10 % O2 ). Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the level of HO-1 mRNA in the rat lung tissue and double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood. Cardiac catheterization was employed to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathological changes of the intra-acinar pulmonary arteries (IAPA). It was found that (1) There was a low level of HO-1 mRNA in normal rat lung tissue, but the level of HO-1 mRNA increased by 2-4 times in the lung tissue of hypoxic rats (P<0.01). The quantity of COHb was 2-3 times those of control group (P<0.01or P<0. 05). These were accompanied by the increased of RVSP and the thickened IAPA; (2) Hemin could keep the HO-1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, thereby ameliorating the pathological changes of IAPA.In conclusion, the upregulation of the expression of HO-1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension.

  10. Punishment sensitivity predicts the impact of punishment on cognitive control.

    Directory of Open Access Journals (Sweden)

    Senne Braem

    Full Text Available Cognitive control theories predict enhanced conflict adaptation after punishment. However, no such effect was found in previous work. In the present study, we demonstrate in a flanker task how behavioural adjustments following punishment signals are highly dependent on punishment sensitivity (as measured by the Behavioural Inhibition System (BIS scale: Whereas low punishment-sensitive participants do show increased conflict adaptation after punishment, high punishment-sensitive participants show no such modulation. Interestingly, participants with a high punishment-sensitivity showed an overall reaction time increase after punishments. Our results stress the role of individual differences in explaining motivational modulations of cognitive control.

  11. Punishment sensitivity predicts the impact of punishment on cognitive control.

    Science.gov (United States)

    Braem, Senne; Duthoo, Wout; Notebaert, Wim

    2013-01-01

    Cognitive control theories predict enhanced conflict adaptation after punishment. However, no such effect was found in previous work. In the present study, we demonstrate in a flanker task how behavioural adjustments following punishment signals are highly dependent on punishment sensitivity (as measured by the Behavioural Inhibition System (BIS) scale): Whereas low punishment-sensitive participants do show increased conflict adaptation after punishment, high punishment-sensitive participants show no such modulation. Interestingly, participants with a high punishment-sensitivity showed an overall reaction time increase after punishments. Our results stress the role of individual differences in explaining motivational modulations of cognitive control.

  12. Development of a real-time imaging system for hypoxic cell apoptosis

    Directory of Open Access Journals (Sweden)

    Go Kagiya

    2016-01-01

    Full Text Available Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3 monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

  13. Sensitivity analysis of small circular cylinders as wake control

    Science.gov (United States)

    Meneghini, Julio; Patino, Gustavo; Gioria, Rafael

    2016-11-01

    We apply a sensitivity analysis to a steady external force regarding control vortex shedding from a circular cylinder using active and passive small control cylinders. We evaluate the changes on the flow produced by the device on the flow near the primary instability, transition to wake. We numerically predict by means of sensitivity analysis the effective regions to place the control devices. The quantitative effect of the hydrodynamic forces produced by the control devices is also obtained by a sensitivity analysis supporting the prediction of minimum rotation rate. These results are extrapolated for higher Reynolds. Also, the analysis provided the positions of combined passive control cylinders that suppress the wake. The latter shows that these particular positions for the devices are adequate to suppress the wake unsteadiness. In both cases the results agree very well with experimental cases of control devices previously published.

  14. The method of establishing the hypoxic SKOV3 cellular model in the research of radiotherapy sensitizer%放疗增敏研究中人卵巢癌SKOV3乏氧细胞模型的建立方法

    Institute of Scientific and Technical Information of China (English)

    宋梦姣; 韩栋梁; 葛宁; 张继青; 曹金发; 刘宏

    2014-01-01

    Objective To investigate the suitable method of establishing the hypoxic SKOV3 cellular model in the research of radiotherapy sensitizer.Methods Human ovarian cancer cell line SKOV3 were divided into three groups:normoxic control group,cobalt chloride group and environmental hypoxia group.Cell proliferation of each group 72 h after single X-ray irradiation(0,2,4,6,8 Gy)were detected by MTT assay.Results Cell proliferation of non-irradiated cells in cobalt chloride group and environmental hypoxia group were significantly lower than that in normoxic control group (t =24.789,196.960,both P<0.01).Cell viability of the cells in normoxic control group and cobalt chloride group were significantly decreased after receiving a single X-ray irradiation of different doses compared with non-irradiated cells in the same group(F=2263.039,3672.044,bothP<0.01) and their cell viability were decreased with the increase of radiation dose,while environmental hypoxia group had no significant change (F=1.412,P>0.05).The cell viability of irradiated cells in environmental hypoxia group were significantly higher than the irradiated cells with the same radiation in normoxic control group and cobalt chloride group(2 Gy:F=61.125; 4 Gy:F=181.825; 6 Gy:F=373.830; 8 Gy:F=2425.510,all P<0.01).Conclusions Cells in environmental hypoxia group were very resistant to radiation.Their radiation sensitivity strikingly decreased and the killing effect of radiation on them was weak.The hypoxic cellular model of environmental hypoxia group was obviously superior to cobalt chloride group.Environmental hypoxia method was more suitable to establish the hypoxic SKOV3 cellular model in the research of radiotherapy sensitizer compared with cobalt chloride.%目的 探讨适用于放疗增敏研究中人卵巢癌SKOV3乏氧细胞模型的建立方法.方法 将人卵巢癌细胞株SKOV3分为常氧对照组、二氯化钴组和环境乏氧组,各组均在X射线单次照射(0、2、4、6、8 Gy)后72 h,

  15. Improved Sensitivity Relations in State Constrained Optimal Control

    Energy Technology Data Exchange (ETDEWEB)

    Bettiol, Piernicola, E-mail: piernicola.bettiol@univ-brest.fr [Université de Bretagne Occidentale, Laboratoire de Mathematiques (France); Frankowska, Hélène, E-mail: frankowska@math.jussieu.fr [Université Pierre et Marie Curie (Paris 6), CNRS and Institut de Mathématiques de Jussieu (France); Vinter, Richard B., E-mail: r.vinter@imperial.ac.uk [Imperial College London, Department of Electrical and Electronic Engineering (United Kingdom)

    2015-04-15

    Sensitivity relations in optimal control provide an interpretation of the costate trajectory and the Hamiltonian, evaluated along an optimal trajectory, in terms of gradients of the value function. While sensitivity relations are a straightforward consequence of standard transversality conditions for state constraint free optimal control problems formulated in terms of control-dependent differential equations with smooth data, their verification for problems with either pathwise state constraints, nonsmooth data, or for problems where the dynamic constraint takes the form of a differential inclusion, requires careful analysis. In this paper we establish validity of both ‘full’ and ‘partial’ sensitivity relations for an adjoint state of the maximum principle, for optimal control problems with pathwise state constraints, where the underlying control system is described by a differential inclusion. The partial sensitivity relation interprets the costate in terms of partial Clarke subgradients of the value function with respect to the state variable, while the full sensitivity relation interprets the couple, comprising the costate and Hamiltonian, as the Clarke subgradient of the value function with respect to both time and state variables. These relations are distinct because, for nonsmooth data, the partial Clarke subdifferential does not coincide with the projection of the (full) Clarke subdifferential on the relevant coordinate space. We show for the first time (even for problems without state constraints) that a costate trajectory can be chosen to satisfy the partial and full sensitivity relations simultaneously. The partial sensitivity relation in this paper is new for state constraint problems, while the full sensitivity relation improves on earlier results in the literature (for optimal control problems formulated in terms of Lipschitz continuous multifunctions), because a less restrictive inward pointing hypothesis is invoked in the proof, and because

  16. Environment-sensitive manipulator control. [real time, decision making computer aided control

    Science.gov (United States)

    Bejczy, A. K.

    1974-01-01

    Environment-sensitive manipulator control (control systems capable of controlling manipulator motion based on real-time response to sensor data obtained during the attempt to perform a requested task) is described, and experiments on (1) proximity control in manipulation and (2) application of an articulated and adaptively controlled hand-to-environment-sensitive manipulator control are reported. The efficiency of such systems is determined by the separation of control and data processing functions between operator and computer.

  17. Sensitive Magnetic Control of Ensemble Nuclear Spin Hyperpolarisation in Diamond

    CERN Document Server

    Wang, Hai-Jing; Avalos, Claudia E; Seltzer, Scott J; Budker, Dmitry; Pines, Alexander; Bajaj, Vikram S

    2012-01-01

    Dynamic nuclear polarisation, which transfers the spin polarisation of electrons to nuclei, is routinely applied to enhance the sensitivity of nuclear magnetic resonance; it is also critical in spintronics, particularly when spin hyperpolarisation can be produced and controlled optically or electrically. Here we show the complete polarisation of nuclei located near the optically-polarised nitrogen-vacancy (NV) centre in diamond. When approaching the ground-state level anti-crossing condition of the NV electron spins, 13C nuclei in the first-shell are polarised in a pattern that depends sensitively and sharply upon the magnetic field. Based on the anisotropy of the hyperfine coupling and of the optical polarisation mechanism, we predict and observe a complete reversal of the nuclear spin polarisation with a few-mT change in the magnetic field. The demonstrated sensitive magnetic control of nuclear polarisation at room temperature will be useful for sensitivity-enhanced NMR, nuclear-based spintronics, and quant...

  18. Stability and Sensitivity Analysis of Fuzzy Control Systems. Mechatronics Applications

    Directory of Open Access Journals (Sweden)

    Radu-Emil Precup

    2006-01-01

    Full Text Available The development of fuzzy control systems is usually performed by heuristicmeans, incorporating human skills, the drawback being in the lack of general-purposedevelopment methods. A major problem, which follows from this development, is theanalysis of the structural properties of the control system, such as stability, controllabilityand robustness. Here comes the first goal of the paper, to present a stability analysismethod dedicated to fuzzy control systems with mechatronics applications based on the useof Popov’s hyperstability theory. The second goal of this paper is to perform the sensitivityanalysis of fuzzy control systems with respect to the parametric variations of the controlledplant for a class of servo-systems used in mechatronics applications based on theconstruction of sensitivity models. The stability and sensitivity analysis methods provideuseful information to the development of fuzzy control systems. The case studies concerningfuzzy controlled servo-systems, accompanied by digital simulation results and real-timeexperimental results, validate the presented methods.

  19. Tracking Hypoxic Signaling in Encapsulated Stem Cells

    Science.gov (United States)

    Sahai, Suchit; McFarland, Rachel; Skiles, Mathew L.; Sullivan, Denise; Williams, Amanda

    2012-01-01

    Oxygen is not only a nutrient but also an important signaling molecule whose concentration can influence the fate of stem cells. This study details the development of a marker of hypoxic signaling for use with encapsulated cells. Testing of the marker was performed with adipose-derived stem cells (ADSCs) in two-dimensional (2D) and 3D culture conditions in varied oxygen environments. The cells were genetically modified with our hypoxia marker, which produces a red fluorescent protein (DsRed-DR), under the control of a hypoxia-responsive element (HRE) trimer. For 3D culture, ADSCs were encapsulated in poly(ethylene glycol)–based hydrogels. The hypoxia marker (termed HRE DsRed-DR) is built on a recombinant adenovirus and ADSCs infected with the marker will display red fluorescence when hypoxic signaling is active. This marker was not designed to measure local oxygen concentration but rather to show how a cell perceives its local oxygen concentration. ADSCs cultured in both 2D and 3D were exposed to 20% or 1% oxygen environments for 96 h. In 2D at 20% O2, the marker signal was not observed during the study period. In 1% O2, the fluorescent signal was first observed at 24 h, with maximum prevalence observed at 96 h as 59%±3% cells expressed the marker. In 3D, the signal was observed in both 1% and 20% O2. The onset of signal in 1% O2 was observed at 4 h, reaching maximum prevalence at 96 h with 76%±4% cells expressing the marker. Interestingly, hypoxic signal was also observed in 20% O2, with 13%±3% cells showing positive marker signal after 96 h. The transcription factor subunit hypoxia inducible factor-1α was tracked in these cells over the same time period by immunostaining and western blot analysis. Immunostaining results in 2D correlated well with our marker at 72 h and 96 h, but 3D results did not correlate well. The western blotting results in 2D and 3D correlated well with the fluorescent marker. The HRE DsRed-DR virus can be used to track

  20. Fuzzy Mixed-Sensitivity Control of Uncertain Nonlinear Induction Motor

    Directory of Open Access Journals (Sweden)

    Vahid Azimi

    2014-06-01

    Full Text Available In this article we investigate on robust mixed-sensitivity H∞ control for speed and torque control of inductional motor (IM. In order to simplify the design procedure the Takagi–Sugeno (T–S fuzzy approach is introduced to solve the nonlinear model Problem. Loop-shaping methodology and Mixed-sensitivity problem are developed to formulate frequency-domain specifications. Then a regional pole-placement output feedback H∞ controller is employed by using linear matrix inequalities(LMIs teqnique for each linear subsystem of IM T-S fuzzy model. Parallel Distributed Compensation (PDC is used to design the controller for the overall system . Simulation results are presented to validate the effectiveness of the proposed controller even in the presence of motor parameter variations and unknown load disturbance.

  1. Fiber Fabry-Perot interferometer with controllable temperature sensitivity.

    Science.gov (United States)

    Zhang, Xinpu; Peng, Wei; Zhang, Yang

    2015-12-01

    We proposed a fiber taper based on the Fabry-Perot (FP) interferometer structure with controllable temperature sensitivity. The FP interferometer is formed by inserting a segment of tapered fiber tip into the capillary and subsequently splicing the other end of the capillary to a single-mode fiber (SMF), the tapered fiber endface, and the spliced face form the FP cavity. Through controlling the inserted tapered fiber length, a series of FP interferometers were made. Because the inserted taper tip has the degree of freedom along the fiber axial, when the FP interferometer is subjected to temperature variation, the thermal expansion of the fiber taper tip will resist the FP cavity length change caused by the evolution of capillary length, and we can control the temperature sensitivity by adjusting the inserted taper length. In this structure, the equivalent thermal expansion coefficient of the FP interferometer can be defined; it was used to evaluate the temperature sensitivity of the FP interferometer, which provides an effective method to eliminate the temperature effect and to enhance other measurement accuracy. We fabricated the FP interferometers and calibrated their temperature characters by measuring the wavelength shift of the resonance dips in the reflection spectrum. In a temperature range of 50°C to 150°C, the corresponding temperature sensitivities can be controlled between 0 and 1.97 pm/°C when the inserted taper is between 75 and 160 μm. Because of its controllable temperature sensitivity, ease of fabrication, and low cost, this FP interferometer can meet different temperature sensitivity requirements in various application areas, especially in the fields which need temperature insensitivity.

  2. Inhibitory masking controls the threshold sensitivity of retinal ganglion cells.

    Science.gov (United States)

    Pan, Feng; Toychiev, Abduqodir; Zhang, Yi; Atlasz, Tamas; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Völgyi, Béla; Akopian, Abram; Bloomfield, Stewart A

    2016-11-15

    Retinal ganglion cells (RGCs) in dark-adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance. Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways. The masking inhibition is subserved by GABAC receptors, probably on bipolar cell axon terminals. The GABAergic masking inhibition appears independent of dopaminergic circuitry that has been shown also to affect RGC sensitivity. The results indicate a novel mechanism whereby inhibition controls the sensitivity of different cohorts of RGCs. This can limit and thereby ensure that appropriate signals are carried centrally in scotopic conditions when sensitivity rather than acuity is crucial. The responses of rod photoreceptors, which subserve dim light vision, are carried through the retina by three independent pathways. These pathways carry signals with largely different sensitivities. Retinal ganglion cells (RGCs), the output neurons of the retina, show a wide range of sensitivities in the same dark-adapted conditions, suggesting a divergence of the rod pathways. However, this organization is not supported by the known synaptic morphology of the retina. Here, we tested an alternative idea that the rod pathways converge onto single RGCs, but inhibitory circuits selectively mask signals so that one pathway predominates. Indeed, we found that application of GABA receptor blockers increased the sensitivity of most RGCs by unmasking rod signals, which were suppressed. Our results indicate that inhibition controls the threshold responses of RGCs under dim ambient light. This mechanism can ensure that appropriate signals cross the bottleneck of the optic nerve in changing stimulus conditions. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  3. Sensitivity and chaos control for the forced nonlinear oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Bashkirtseva, Irina [Department of Mathematics, Ural State University, 620083 Ekaterinburg (Russian Federation); Ryashko, Lev [Department of Mathematics, Ural State University, 620083 Ekaterinburg (Russian Federation)] e-mail: lev.ryashko@usu.ru

    2005-12-01

    This paper is devoted to study the problem of controlling chaos for forced nonlinear dynamic systems. We suggest a new control technique based on sensitivity analysis. With the help of approximation of nonequilibrium quasipotential, stochastic sensitivity function (SSF) is constructed. This function is used as basic tool of a quantitative description for a system response on the random external disturbances. The possibilities of SSF to predict chaotic dynamics for the periodic and stochastic forced Brusselator are shown. The problem of chaos control based on SSF is considered. A design of attractors with the desired features by feedback regulator is discussed. Analysis of controllability and effective technique for regulator synthesis is presented. An example of suppressing chaos for Brusselator is considered.

  4. Optimal parametric sensitivity control for a fed-batch reactor

    NARCIS (Netherlands)

    Stigter, J.D.; Keesman, K.J.

    2001-01-01

    The paper presents a method to derive an optimal parametric sensitivity controller for optimal estimation of a set of parameters in an experiment. The method is demonstrated for a fed batch bio-reactor case study for optimal estimation of the saturation constant Ks and, albeit intuitively, the param

  5. Optimal parametric sensitivity control of a fed-batch reactor

    NARCIS (Netherlands)

    Stigter, J.D.; Keesman, K.J.

    2004-01-01

    The paper presents an optimal parametric sensitivity controller for estimation of a set of parameters in an experiment. The method is demonstrated for a fed-batch bioreactor case study for optimal estimation of the half-saturation constant KS and the parameter combination µmaxX/Y in which µmax is th

  6. Sensitivity method for integrated structure/active control law design

    Science.gov (United States)

    Gilbert, Michael G.

    1987-01-01

    The development is described of an integrated structure/active control law design methodology for aeroelastic aircraft applications. A short motivating introduction to aeroservoelasticity is given along with the need for integrated structures/controls design algorithms. Three alternative approaches to development of an integrated design method are briefly discussed with regards to complexity, coordination and tradeoff strategies, and the nature of the resulting solutions. This leads to the formulation of the proposed approach which is based on the concepts of sensitivity of optimum solutions and multi-level decompositions. The concept of sensitivity of optimum is explained in more detail and compared with traditional sensitivity concepts of classical control theory. The analytical sensitivity expressions for the solution of the linear, quadratic cost, Gaussian (LQG) control problem are summarized in terms of the linear regulator solution and the Kalman Filter solution. Numerical results for a state space aeroelastic model of the DAST ARW-II vehicle are given, showing the changes in aircraft responses to variations of a structural parameter, in this case first wing bending natural frequency.

  7. [Hemo- and neurodynamics of the human brain during exposure to moderate hypoxic hypoxia].

    Science.gov (United States)

    Alekseev, D A; Zubarev, A F; Krupina, T N; Iarullin, Kh Kh; Kuznets, E I

    1984-01-01

    Synchronous electro- and rheoencephalography were used to study tolerance to moderate hypoxic hypoxia for 30 min at an altitude of 5000 m without additional oxygen supply. As test subject, men with autonomic-vascular dystonia (29-39 years old), 15 men over 40 (41-56 years old), and 16 essentially healthy controls (23-36 years old) were used. The aged volunteers (41-56 years old) did not differ from the controls with respect to their tolerance to hypoxic hypoxia. The men with early symptoms of hypertonic-type dystonia also showed high tolerance to hypoxic hypoxia. The subjects with hypotonic-type dystonia displayed lower tolerance.

  8. Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Chapleau, M W; Wilson, L B; Gregory, T J; Levitzky, M G

    1988-02-01

    Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. Left pulmonary artery (QL) and main pulmonary artery (QT) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. QL/QT averaged 46 +/- 4, 29 +/- 2, and 36 +/- 4% during bilateral O2 ventilation (control), left lung N2 ventilation, and left lung N2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, QL/QT averaged 45 +/- 4, 27 +/- 3, and 28 +/- 2% during the same conditions. QL/QT decreased significantly from control (P less than 0.05) during left lung N2 alone but did not decrease during left lung N2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, QL/QT decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selective stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect.

  9. Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis.

    Science.gov (United States)

    Nanduri, Jayasri; Makarenko, Vladislav; Reddy, Vaddi Damodara; Yuan, Guoxiang; Pawar, Anita; Wang, Ning; Khan, Shakil A; Zhang, Xin; Kinsman, Brian; Peng, Ying-Jie; Kumar, Ganesh K; Fox, Aaron P; Godley, Lucy A; Semenza, Gregg L; Prabhakar, Nanduri R

    2012-02-14

    Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.

  10. [Multicenter program for the integrated care of newborns with perinatal hypoxic-ischemic insult (ARAHIP)].

    Science.gov (United States)

    Arnáez, J; Vega, C; García-Alix, A; Gutiérrez, E P; Caserío, S; Jiménez, M P; Castañón, L; Esteban, I; Hortelano, M; Hernández, N; Serrano, M; Prada, T; Diego, P; Barbadillo, F

    2015-03-01

    Newborns with perinatal indicators of a potential hypoxic-ischemic event require an integrated care in order to control the aggravating factors of brain damage, and the early identification of candidates for hypothermia treatment. The application of a prospective, populational program that organizes and systematizes medical care during the first 6 hours of life to all newborns over 35 weeks gestational age born with indicators of a perinatal hypoxic-ischemic insult. The program includes 12 hospitals (91,217 m(2)); two level i centers, five level ii centers, and five level iii hospitals. The program establishes four protocols: a) detection of the newborn with a potential hypoxic-ischemic insult, b) surveillance of the neurological repercussions and other organ involvement, c) control and treatment of complications, d) procedures and monitoring during transport. From June 2011 to June 2013, 213 of 32325 newborns above 35 weeks gestational age met the criteria of a potential hypoxic-ischemic insult (7.4/1000), with 92% of them being cared for following the program specifications. Moderate-severe hypoxic-ischemic encephalopathy was diagnosed in 33 cases (1/1,000), and 31 out of the 33 received treatment with hypothermia (94%). The program for the Integrated Care of Newborns with Perinatal Hypoxic-Ischemic Insult has led to providing a comprehensive care to the newborns with a suspected perinatal hypoxic-ischemic insult. Aggravators of brain damage have been controlled, and cases of moderate-severe hypoxic-ischemic encephalopathy have been detected, allowing the start of hypothermia treatment within the first six hours of life. Populational programs are fundamental to reducing the mortality and morbidity of hypoxic-ischemic encephalopathy. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  11. The hypoxic tumour microenvironment and metastatic progression.

    Science.gov (United States)

    Subarsky, Patrick; Hill, Richard P

    2003-01-01

    The microenvironment of solid tumours contains regions of poor oxygenation and high acidity. Growing evidence from clinical and experimental studies points to a fundamental role for hypoxia in metastatic progression. Prolonged hypoxia increases genomic instability, genomic heterogeneity, and may act as a selective pressure for tumour cell variants. Hypoxia can also act in an epigenetic fashion, altering the expression of genes. Hypoxia-induced changes in gene expression alter non-specific stress responses, anaerobic metabolism, angiogenesis, tissue remodeling, and cell-cell contacts. Experimental studies have demonstrated that inhibition of proteins involved in these processes can modify metastasis formation, suggesting a causal role in metastatic progression. Recent advances in high-throughput screening techniques have allowed identification of many hypoxia-induced genes that are involved in the processes associated with metastasis. Here we review the epigenetic control of gene expression by the hypoxic microenvironment and its potential contribution to metastatic progression.

  12. Chick embryos have the same pattern of hypoxic lower-brain activation as fetal mammals.

    Science.gov (United States)

    Landry, Jeremy P; Hawkins, Connor; Lee, Aaron; Coté, Alexandra; Balaban, Evan; Pompeiano, Maria

    2016-01-01

    cFos expression (indicating a particular kind of neuronal activation) was examined in embryonic day (E) 18 chick embryos after exposure to 4 h of either normoxia (21% O2), modest hypoxia (15% O2), or medium hypoxia (10% O2). Eight regions of the brainstem and hypothalamus were surveyed, including seven previously shown to respond to hypoxia in late-gestation mammalian fetuses (Breen et al., 1997; Nitsos and Walker, 1999b). Hypoxia-related changes in chick embryo brain activation mirrored those found in fetal mammals with the exception of the medullary Raphe, which showed decreased hypoxic activation, compared with no change in mammals. This difference may be explained by the greater anapyrexic responses of chick embryos relative to mammalian fetuses. Activation in the A1/C1 region was examined in more detail to ascertain whether an O2-sensitive subpopulation of these cells containing heme oxygenase 2 (HMOX2) may drive hypoxic brain responses before the maturation of peripheral O2-sensing. HMOX2-positive and -negative catecholaminergic cells and interdigitating noncatecholaminergic HMOX2-positive cells all showed significant changes in cFos expression to hypoxia, with larger population responses seen in the catecholaminergic cells. Hypoxia-induced activation of lower-brain regions studied here was significantly better correlated with activation of the nucleus of the solitary tract (NTS) than with that of HMOX2-containing A1/C1 neurons. Together, these observations suggest that (1) the functional circuitry controlling prenatal brain responses to hypoxia is strongly conserved between birds and mammals, and (2) NTS neurons are a more dominant driving force for prenatal hypoxic cFos brain responses than O2-sensing A1/C1 neurons.

  13. DESIGNING REDUCED-ORDER CONTROLLERS OF MIXED SENSITIVITY PROBLEM FOR FLIGHT CONTROL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on linear matrix inequalities (LMI), the design method of reduced-order controllers of mixed sensitivity problem is studied for flight control systems. It is shown that there exists a controller with order not greater than the difference between the generalized plant order and the number of independent control variables, if the mixed sensitivity problem is solvable for strict regular flight control plants. The proof is constructive, and an approach to design such a controller can be obtained in terms of a pair of feasible solution to the well-known 3 LMI. Finally, an example of mixed sensitivity problem for a flight control system is given to demonstrate practice of the approach.

  14. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

    Science.gov (United States)

    Lu, Yingli; Feng, Lianshi; Xie, Minhao; Zhang, Li; Xu, Jianfang; He, Zihong; You, Tongjian

    2016-01-01

    Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n = 10 each): control, sedentary hypoxic living for 1–4 weeks (SH1, SH2, SH3, and SH4), living, and exercise training in normoxic conditions for 1–4 weeks (TN1, TN2, TN3, and TN4), and living and exercise training in hypoxic conditions for 1–4 weeks (TN1, TN2, TN3, and TN4). Epididymal adipose tissue expression levels of leptin and leptin receptor were determined Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3–4 weeks resulted in lower Lee index (P exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions. PMID:27932989

  15. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats.

    Science.gov (United States)

    Lu, Yingli; Feng, Lianshi; Xie, Minhao; Zhang, Li; Xu, Jianfang; He, Zihong; You, Tongjian

    2016-01-01

    Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n = 10 each): control, sedentary hypoxic living for 1-4 weeks (SH1, SH2, SH3, and SH4), living, and exercise training in normoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4), and living and exercise training in hypoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4). Epididymal adipose tissue expression levels of leptin and leptin receptor were determined Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P leptin and leptin receptor (P adipose tissue. Conclusion: In a rodent model of altitude training, living, and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  16. Metabolites of Hypoxic Cardiomyocytes Induce the Migration of Cardiac Fibroblasts.

    Science.gov (United States)

    Shi, Huairui; Zhang, Xuehong; He, Zekun; Wu, Zhiyong; Rao, Liya; Li, Yushu

    2017-01-01

    The migration of cardiac fibroblasts to the infarct region plays a major role in the repair process after myocardial necrosis or damage. However, few studies investigated whether early hypoxia in cardiomyocytes induces the migration of cardiac fibroblasts. The purpose of this study was to assess the role of metabolites of early hypoxic cardiomyocytes in the induction of cardiac fibroblast migration. Neonatal rat heart tissue was digested with a mixture of trypsin and collagenase at an appropriate ratio. Cardiomyocytes and cardiac fibroblasts were cultured via differential adhesion. The cardiomyocyte cultures were subjected to hypoxia for 2, 4, 6, 8, 10, and 12 h. The supernatants of the cardiomyocyte cultures were collected to determine the differences in cardiac fibroblast migration induced by hypoxic cardiomyocyte metabolites at various time points using a Transwell apparatus. Meanwhile, ELISA was performed to measure TNF-α, IL-1β and TGF-β expression levels in the cardiomyocyte metabolites at various time points. The metabolites of hypoxic cardiomyocytes significantly induced the migration of cardiac fibroblasts. The induction of cardiac fibroblast migration was significantly enhanced by cardiomyocyte metabolites in comparison to the control after 2, 4, and 6 h of hypoxia, and the effect was most significant after 2 h. The expression levels of TNF-α, IL-1β, IL-6, and TGF-β were substantially increased in the metabolites of cardiomyocytes, and neutralization with anti-TNF-α and anti-IL-1β antibodies markedly reduced the induction of cardiac fibroblast migration by the metabolites of hypoxic cardiomyocytes. The metabolites of early hypoxic cardiomyocytes can induce the migration of cardiac fibroblasts, and TNF-α and IL-1β may act as the initial chemotactic inducers. © 2017 The Author(s) Published by S. Karger AG, Basel.

  17. Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.

    Science.gov (United States)

    Weisbrod, C J; Minson, C T; Joyner, M J; Halliwill, J R

    2001-12-01

    1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 85%) in eight healthy men and women (18-26 years) after selective alpha-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after phentolamine (compared to +16.8 +/- 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by approximately 50%, but dilatation was still present (+24.7 +/- 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 +/- 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional alpha-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by beta-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

  18. Sensitivity of Eigenvalues to Nonsymmetrical, Dissipative Control Matrices

    Directory of Open Access Journals (Sweden)

    Vernon H. Neubert

    1993-01-01

    Full Text Available Dissipation of energy in vibrating structures can be accomplished with a combination of passive damping and active, constant gain, closed loop control forces. The matrix equations are Mz¨+Cz˙+Kz=−Gz˙. With conventional viscous damping, the damping force is proportional to relative velocity, with Fi=Ciiz˙i−Cijz˙j, where Cii=Cij but the subscripts show the position of the number in the C matrix. For a dashpot connected directly to ground, Fi=Ciiz˙i. Thus there is a definite pattern to the positions of numbers in the ith and jth rows of the C matrix, that is, a positive number on the diagonal is paired with an equal negative number, or zero, off the diagonal. With the control matrix G, it is here assumed that the positioning of individual controllers and sensors is flexible, with Fi=Ciiz˙i or Fi=Cijz˙j, the latter meaning that the control force at i is proportional to the velocity sensed at j. Thus the problem addressed herein is how the individual elements in the G matrix affect the modal eigenvalues. Two methods are discussed for finding the sensitivities, the classical method based on the products of eigenvectors and a new method, derived during the present study, involving the derivatives of the invariants in the similarity transformation. Examples are presented for the sensitivities of the complex eigenvalues of the form λr=−ζrwr+iwDr to individual elements in the G matrix, to combinations of elements, and to a combination of passive damping and active control. Systems with two, three, and eight degrees of freedom are investigated.

  19. Space Shuttle Orbiter entry guidance and control system sensitivity analysis

    Science.gov (United States)

    Stone, H. W.; Powell, R. W.

    1976-01-01

    An approach has been developed to determine the guidance and control system sensitivity to off-nominal aerodynamics for the Space Shuttle Orbiter during entry. This approach, which uses a nonlinear six-degree-of-freedom interactive, digital simulation, has been applied to both the longitudinal and lateral-directional axes for a portion of the orbiter entry. Boundary values for each of the aerodynamic parameters have been identified, the key parameters have been determined, and system modifications that will increase system tolerance to off-nominal aerodynamics have been recommended. The simulations were judged by specified criteria and the performance was evaluated by use of key dependent variables. The analysis is now being expanded to include the latest shuttle guidance and control systems throughout the entry speed range.

  20. Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results.

    Science.gov (United States)

    Artzi, Moran; Sira, Liat Ben; Bassan, Haim; Gross-Tsur, Varda; Berger, Irit; Marom, Ronella; Leitner, Yael; Bental, Yoram; Shiff, Yakov; Geva, Ronny; Weinstein, Maya; Bashat, Dafna Ben

    2011-10-01

    Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.

  1. Vitreous Mediators in Retinal Hypoxic Diseases

    Directory of Open Access Journals (Sweden)

    Roberto dell'Omo

    2013-01-01

    Full Text Available The causes of retinal hypoxia are many and varied. Under hypoxic conditions, a variety of soluble factors are secreted into the vitreous cavity including growth factors, cytokines, and chemokines. Cytokines, which usually serve as signals between neighboring cells, are involved in essentially every important biological process, including cell proliferation, inflammation, immunity, migration, fibrosis, tissue repair, and angiogenesis. Cytokines and chemokines are multifunctional mediators that can direct the recruitment of leukocytes to sites of inflammation, promote the process, enhance immune responses, and promote stem cell survival, development, and homeostasis. The modern particle-based flow cytometric analysis is more direct, stable and sensitive than the colorimetric readout of the conventional ELISA but, similar to ELISA, is influenced by vitreous hemorrhage, disruption of the blood-retina barrier, and high serum levels of a specific protein. Finding patterns in the expression of inflammatory cytokines specific to a particular disease can substantially contribute to the understanding of its basic mechanism and to the development of a targeted therapy.

  2. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

    Science.gov (United States)

    Harding, Benjamin; Conception, Katherine; Li, Yong; Zhang, Lubo

    2016-01-01

    Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis) and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI) insult in neonatal rats via intracerebroventricular (ICV) injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS) sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional inflammatory injury, such

  3. RELAXANT EFFECTS OF VASOACTIVE INTESTINAL PEPTIDE ON PULMONARY ARTERY IN CHRONICALLY HYPOXIC RATS

    Institute of Scientific and Technical Information of China (English)

    陈玉玲; 罗慰慈; 蔡英年

    1996-01-01

    The object of this study is to investigate the effect of VIP on pulmonary artery of chronically hypoxic rats. It was shown that chronic hypoxla depressed significantly pulmnonary artery relaxation induced by VIP as compared with those of control (Psensitivity and reactivity of pulmonary artery to VIP.

  4. Neuropsychological outcomes of pediatric burn patients who sustained hypoxic episodes.

    Science.gov (United States)

    Rosenberg, Marta; Robertson, Carrie; Murphy, Kevin D; Rosenberg, Laura; Mlcak, Ronald; Robert, Rhonda S; Herndon, David N; Meyer, Walter J

    2005-11-01

    The neuropsychological outcomes of children who suffered hypoxic episodes following their burns are not completely understood and vary depending on the nature and severity of the episode. A retrospective review of youth that were admitted to this acute burn care facility over the past 20 years was conducted to identify the extent of cognitive and affective difficulties. Thirty-nine children who sustained hypoxic injuries related to their burns were compared with 21 controls that were matched for age, TBSA, and time of injury. Approximately a third of the children who survived from the hypoxia group continued to have long-term cognitive and emotional difficulties. For those who recovered reasonably well, no differences were found from the matched burned controls. These results probably underestimate the true extent of neuropsychological difficulties experienced by these youth given that detailed cognitive testing was not routinely performed. Prospective studies are needed to further characterize the full nature of difficulties and outcomes associated with burn related hypoxic injuries.

  5. Cerebrospinal lfuid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury

    Institute of Scientific and Technical Information of China (English)

    Yan-bo Zhang; Zheng-dong Guo; Mei-yi Li; Si-jie Li; Jing-zhong Niu; Ming-feng Yang; Xun-ming Ji; Guo-wei Lv

    2015-01-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral isch-emic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal lfuid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal lfuid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expres-sion in neurons from newborn rats.

  6. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

    Science.gov (United States)

    Zhang, Yan-Bo; Guo, Zheng-Dong; Li, Mei-Yi; Li, Si-Jie; Niu, Jing-Zhong; Yang, Ming-Feng; Ji, Xun-Ming; Lv, Guo-Wei

    2015-09-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

  7. Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Stivaros, Stavros M. [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom); University of Manchester, Centre for Imaging Sciences, Institute of Population Health, Manchester (United Kingdom); Radon, Mark R. [The Walton Centre NHS Foundation Trust, Department of Neuroradiology, Liverpool (United Kingdom); Mileva, Reneta; Gledson, Ann; Keane, John A. [University of Manchester, School of Computer Science, Manchester (United Kingdom); Connolly, Daniel J.A.; Batty, Ruth [Sheffield Children' s Hospital NHS Foundation Trust, Department of Neuroradiology, Sheffield (United Kingdom); Cowell, Patricia E. [University of Sheffield, Department of Human Communication Sciences, Sheffield (United Kingdom); Hoggard, Nigel; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Wright, Neville B.; Tang, Vivian [Manchester Academic Health Science Centre, Academic Unit of Paediatric Radiology, Royal Manchester Children' s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester (United Kingdom)

    2016-01-15

    Birth-related acute profound hypoxic-ischaemic brain injury has specific patterns of damage including the paracentral lobules. To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Study subjects included 13 children with proven acute profound hypoxic-ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. There was statistically significant narrowing of the mid-posterior body and genu of the corpus callosum in children with hypoxic-ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Focal volume loss is seen in the corpus callosum of children with hypoxic-ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic-ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic-ischaemic brain injury. (orig.)

  8. Hypoxic preconditioning involves system Xc- regulation in mouse neural stem cells.

    Science.gov (United States)

    Sims, Brian; Clarke, Melinda; Francillion, Ludwig; Kindred, Elijah; Hopkins, Elana Shuford; Sontheimer, Harald

    2012-03-01

    In animals, hypoxic preconditioning has been used as a form of neuroprotection. The exact mechanism involved in neuroprotective hypoxic preconditioning has not been described, yet could be valuable for possible neuroprotective strategies. The overexpression of the cystine-glutamate exchanger, system Xc-, has been demonstrated as being neuroprotective (Shih, Erb et al. 2006). Here, using immunohistochemistry, we demonstrate that C57BL/6 mice exposed to hypoxia showed an increase in system Xc- expression, with the highest level of intensity in the hippocampus. Western Blot analysis also showed an almost 2-fold increase in system Xc- protein in hypoxia-exposed versus control mice. The mRNA for the regulatory subunit of system Xc-, xCT, and the xCT/actin ratio were also increased under hypoxic conditions. Experiments using hypoxia-inducible factor (HIF-1α) siRNA showed a statistically significant decrease in HIF-1α and system Xc- expression. Under hypoxic conditions, system Xc- activity, as determined by cystine uptake, increased 2-fold. Importantly, hypoxic preconditioning was attenuated in neural stem cells by pharmacological inhibition of system Xc- activity with S4-carboxyphenylglycine. These data provide the first evidence of hypoxic regulation of the cystine glutamate exchanger system Xc-.

  9. Mesenchymal stem cells from a hypoxic culture improve and engraft Achilles tendon repair.

    Science.gov (United States)

    Huang, Tung-Fu; Yew, Tu-Lai; Chiang, En-Rung; Ma, Hsiao-Li; Hsu, Chih-Yuan; Hsu, Shan-Hui; Hsu, Yuan-Tong; Hung, Shih-Chieh

    2013-05-01

    Bone marrow-derived mesenchymal stem cells (MSCs) from humans cultured under hypoxic conditions increase bone healing capacity. Rat MSCs cultured under hypoxic conditions increase the tendon healing potential after transplantation into injured Achilles tendons. Controlled laboratory study. Biomechanical testing, histological analysis, and bromodeoxyuridine (BrdU) labeling/collagen immunohistochemistry were performed to demonstrate that augmentation of an Achilles tendon rupture site with hypoxic MSCs increases healing capacity compared with normoxic MSCs and controls. Fifty Sprague-Dawley rats were used for the experiments, with 2 rats as the source of bone marrow MSCs. The cut Achilles tendons in the rats were equally divided into 3 groups: hypoxic MSC, normoxic MSC, and nontreated (vehicle control). The uncut tendons served as normal uncut controls. Outcome measures included mechanical testing in 24 rats, histological analysis, and BrdU labeling/collagen immunohistochemistry in another 24 rats. The ultimate failure load in the hypoxic MSC group was significantly greater than that in the nontreated or normoxic MSC group at 2 weeks after incision (2.1 N/mm(2) vs 1.1 N/mm(2) or 1.9 N/mm(2), respectively) and at 4 weeks after incision (5.5 N/mm(2) vs 1.7 N/mm(2) or 2.7 N/mm(2), respectively). The ultimate failure load in the hypoxic MSC group at 4 weeks after incision (5.5 N/mm(2)) was close to but still significantly less than that of the uncut tendon (7.2 N/mm(2)). Histological analysis as determined by the semiquantitative Bonar histopathological grading scale revealed that the hypoxic MSC group underwent a significant improvement in Achilles tendon healing both at 2 and 4 weeks when compared with the nontreated or normoxic MSC group via statistical analysis. Immunohistochemistry further demonstrated that the hypoxic and normoxic MSC groups had stronger immunostaining for type I and type III collagen than did the nontreated group both at 2 and 4 weeks after

  10. Space Telescope Sensitivity and Controls for Exoplanet Imaging

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark

    2012-01-01

    Herein we address design considerations and outline requirements for space telescopes with capabilities for high contrast imaging of exoplanets. The approach taken is to identify the span of potentially detectable Earth-sized terrestrial planets in the habitable zone of the nearest stars within 30 parsecs and estimate their inner working angles, flux ratios, SNR, sensitivities, wavefront error requirements and sensing and control times parametrically versus aperture size. We consider 1, 2, 4, 8 and 16-meter diameter telescope apertures. The achievable science, range of telescope architectures, and the coronagraphic approach are all active areas of research and are all subject to change in a rapidly evolving field. Thus, presented is a snapshot of our current understanding with the goal of limiting the choices to those that appear currently technically feasible. We describe the top-level metrics of inner working angle, contrast and photometric throughput and explore how they are related to the range of target stars. A critical point is that for each telescope architecture and coronagraphic choice the telescope stability requirements have differing impacts on the design for open versus closed-loop sensing and control.

  11. Hypsometric control on glacier mass balance sensitivity in Alaska

    Science.gov (United States)

    McGrath, D.; Sass, L.; Arendt, A. A.; O'Neel, S.; Kienholz, C.; Larsen, C.; Burgess, E. W.

    2015-12-01

    Mass loss from glaciers in Alaska is dominated by strongly negative surface balances, particularly on small, continental glaciers but can be highly variable from glacier to glacier. Glacier hypsometry can exert significant control on mass balance sensitivity, particularly if the equilibrium line altitude (ELA) is in a broad area of low surface slope. In this study, we explore the spatial variability in glacier response to future climate forcings on the basis of hypsometry. We first derive mass balance sensitivities (30-70 m ELA / 1° C and 40-90 m ELA / 50% decrease in snow accumulation) from the ~50-year USGS Benchmark glaciers mass balance record. We subsequently assess mean climate fields in 2090-2100 derived from the IPCC AR5/CMIP5 RCP 6.0 5-model mean. Over glaciers in Alaska, we find 2-4° C warming and 10-20% increase in precipitation relative to 2006-2015, but a corresponding 0-50% decrease in snow accumulation due to rising temperatures. We assess changes in accumulation area ratios (AAR) to a rising ELA using binned individual glacier hypsometries. For an ELA increase of 150 m, the mean statewide AAR drops by 0.45, representing a 70% reduction in accumulation area on an individual glacier basis. Small, interior glaciers are the primary drivers of this reduction and for nearly 25% of all glaciers, the new ELA exceeds the glacier's maximum elevation, portending eventual loss. The loss of small glaciers, particularly in the drier interior of Alaska will significantly modify streamflow properties (flashy hydrographs, earlier and reduced peak flows, increased interannual variability, warmer temperatures) with poorly understood downstream ecosystem and oceanographic impacts.

  12. Pulmonary hypoxic vasoconstriction: how strong? How fast?

    Science.gov (United States)

    Sheehan, D. W.; Klocke, R. A.; Farhi, L. E.

    1992-01-01

    We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

  13. PID Controller Design Based on the Time Domain Information of Robust IMC Controller Using Maximum Sensitivity

    Institute of Scientific and Technical Information of China (English)

    JIN Qibing; LIU Qie; WANG Qi; TIAN Yuqi; WANG Yuanfei

    2013-01-01

    The IMC (Internal Model Control) controller based on robust tuning can improve the robustness and dynamic performance of the system.In this paper,the robustness degree of the control system is investigated based on Maximum Sensitivity (Ms) in depth.And the analytical relationship is obtained between the robustness specification and controller parameters,which gives a clear design criterion to robust IMC controller.Moreover,a novel and simple IMC-PID (Proportional-Integral-Derivative) tuning method is proposed by converting the IMC controller to PID form in terms of the time domain rather than the frequency domain adopted in some conventional IMC-based methods.Hence,the presented IMC-PID gives a good performance with a specific robustness degree.The new IMC-PID method is compared with other classical IMC-PID rules,showing the flexibility and feasibility for a wide range of plants.

  14. Concerted modulation of alanine and glutamate metabolism in young Medicago truncatula seedlings under hypoxic stress.

    Science.gov (United States)

    Limami, Anis M; Glévarec, Gaëlle; Ricoult, Claudie; Cliquet, Jean-Bernard; Planchet, Elisabeth

    2008-01-01

    The modulation of primary nitrogen metabolism by hypoxic stress was studied in young Medicago truncatula seedlings. Hypoxic seedlings were characterized by the up-regulation of glutamate dehydrogenase 1 (GDH1) and mitochondrial alanine aminotransferase (mAlaAT), and down-regulation of glutamine synthetase 1b (GS1b), NADH-glutamate synthase (NADH-GOGAT), glutamate dehydrogenase 3 (GDH3), and isocitrate dehydrogenase (ICDH) gene expression. Hypoxic stress severely inhibited GS activity and stimulated NADH-GOGAT activity. GDH activity was lower in hypoxic seedlings than in the control, however, under either normoxia or hypoxia, the in vivo activity was directed towards glutamate deamination. (15)NH(4) labelling showed for the first time that the adaptive reaction of the plant to hypoxia consisted of a concerted modulation of nitrogen flux through the pathways of both alanine and glutamate synthesis. In hypoxic seedlings, newly synthesized (15)N-alanine increased and accumulated as the major amino acid, asparagine synthesis was inhibited, while (15)N-glutamate was synthesized at a similar rate to that in the control. A discrepancy between the up-regulation of GDH1 expression and the down-regulation of GDH activity by hypoxic stress highlighted for the first time the complex regulation of this enzyme by hypoxia. Higher rates of glycolysis and ethanol fermentation are known to cause the fast depletion of sugar stores and carbon stress. It is proposed that the expression of GDH1 was stimulated by hypoxia-induced carbon stress, while the enzyme protein might be involved during post-hypoxic stress contributing to the regeneration of 2-oxoglutarate via the GDH shunt.

  15. IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy.

    Science.gov (United States)

    Aly, Hany; Khashaba, Mohamed T; El-Ayouty, Mostafa; El-Sayed, Osman; Hasanein, Bothina M

    2006-04-01

    The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates is not fully defined. We hypothesize that interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) correlate with the severity of brain injury and can predict neurological deficits in infants who suffered from hypoxic ischemic encephalopathy (HIE). A prospective study was conducted on 24 term infants diagnosed with HIE and 13 controls. HIE was clinically classified into mild, moderate and severe according to Sarnat and Sarnat grading. Blood and CSF samples were obtained from all infants in the first 24h of life as part of routine investigations for suspected meningitis and/or sepsis. Neurological examination and Denver Developmental Screening Test II (DDST II) were performed at 6 and 12 months of life. IL-1beta, IL-6 and TNF-alpha were all significantly increased in HIE infants when compared to control. IL-1beta in the CSF correlated with the severity of HIE (r=0.61, P=0.001) more than IL-6 (r=0.45, P=0.004) or TNF-alpha (r=0.47, P=0.003). IL-1beta exhibited the highest CSF/serum ratio among the three studied cytokines suggesting its local release in the brain after the initial hypoxic injury. Abnormal neurological findings and/or abnormal DDST II at 6 and 12 months were best predicted by IL-1beta in the CSF (sensitivity=88% and specificity=80%). This study confirms the role of IL-1beta in the ongoing neuronal injury that occurs in the latent phase following the original HIE insult.

  16. [STRESS AND INFARCT LIMITING EFFECTS OF EARLY HYPOXIC PRECONDITIONING].

    Science.gov (United States)

    Lishmanov, Yu B; Maslov, L N; Sementsov, A S; Naryzhnaya, N V; Tsibulnikov, S Yu

    2015-09-01

    It was established that early hypoxic preconditioning is an adaptive state different from eustress and distress. Hypoxic preconditioning has the cross effects, increasing the tolerance of the heart to ischemia-reperfusion and providing antiulcerogenic effect during immobilization stress.

  17. Acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats

    Institute of Scientific and Technical Information of China (English)

    程德云; 陈文彬; 莫晓能

    2002-01-01

    Objective To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation. Methods Twenty rats were exposed to hypoxic conditions for 3 weeks. Ten rats were used as normoxic controls. We administered Tet pulmonary targeting microspheres to 10 hypoxic rats and Tet aqueous solution to 10 hypoxic rats and the 10 control rats. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. Results Rats exposed to hypoxia developed pulmonary hypertension. The decrease in mPAP in rats treated with Tet pulmonary targeting microspheres was significantly greater than that in rats receiving Tet aqueous solution (P<0.05), and the effects were longer with Tet pulmonary targeting microspheres. Moreover, Tet pulmonary targeting microspheres, unlike Tet aqueous solution, did not decrease mSBP. Conclusion Tet pulmonary targeting microspheres were more effective than Tet aqueous solution in treating hypoxic pulmonary hypertension and acted selectively on the pulmonary circulation.

  18. Evaluación de metales redox-sensitivos como proxies de paleoxigenación en un ambiente marino hipóxico del norte de Chile Redox-sensitive metals evaluation as proxis of paleoxygenation in a hypoxic marine environment of northern Chile

    Directory of Open Access Journals (Sweden)

    JORGE VALDÉS

    2004-03-01

    metales registrada entre las muestras de la parte superior de los testigos (correspondientes a antes de 1996 y las muestras superficiales (correspondientes al año 2000 y tomadas en la misma zona de los testigos, pueden ser atribuidas al efecto de El Niño 1997-1998, el cual provocó un brusco descenso en el flujo de metales (principalmente Ni y Cd hacia los sedimentos, debido a una condición más oxigenada de la columna de agua. Este trabajo muestra que de los cinco metales analizados, solo en Ni y el Cd parecen tener un potencial como indicadores de paleoxigenación en la bahía Mejillones. Sin embargo, su uso está restringido para identificar cambios extremos desde una condición anóxica a una óxica en los sedimentos de fondo de esta bahía.The distribution of molybdenum, cadmium, zinc, vanadium and nickel, all redox-sensitive metals, was analyzed under a spatial (surface sediment samples and temporal (core samples perspective, in order to identify the potential of these metals for paleoxygenation interpretations in Mejillones bay, a hypoxic environment of northern Chile. Lithogenic supply (according to aluminum was discarded. Biogenic flux is not the unique factor that controls the mechanism of metals preservation in sediments of this bay. Spatial variation of metals concentration was investigated in relation to the bottom water oxygenation in each sampling station. Results showed that only Ni and Cd present a strong correlation with dissolved oxygen, increasing their concentration toward the deepest area of the bay were an oxygen minimum zone prevails with values around 0.02 mL L-1. The temporal variation in redox-sensitive metals, recorded in three sediments core covering the last 2,000 years, showed that bottom oxygenation of the bay changed from a more oxygenated environment in the past to a less oxygenated environment at present. A biogenic flux across a very well developed oxycline, associated to an anoxic sediment-water interface, are proposed to be the

  19. Monitoring of neurological parameters in newborns with hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Đinđić Jasmina

    2006-01-01

    Full Text Available Asphyxia i a condition caused by lack of oxygen in tissues and organs. The basic pathogenic mechanisms of asphyxia are: 1hypoxemia, 2 ischemia. The effects of perinatal asphyxia on the brain of a neonatal baby are critical in development of hypoxic-ischemic encephalopathy. The diagnosis of hypoxic-ischemic encephalopathy is based on clinical data including course of pregnancy and delivery (Apgar score and especially on the neurological status of the newborn (consciousness, tonus, convulsions, reflexes, vegetative functions, etc. and it can be confirmed by biochemical analysis and neurological examinations. The aim of this paper is to determine the importance of prenatal and perinatal risk factors for hypoxic-ischemic encephalopathy, as well as their effects on the development of neurological complications and further neurological problems. The research included 148 newborn infants born in the period from January 1, 1996 to January 1, 1999, with gestational age of 27 to 42 weeks, with hypoxic ischemic lesions of the central nervosus system. The control group included 58 children of the same age and the same gestation, with generalized hypotonia ("floppy infant" but without any signs of hypoxic ischemic lesions of the central nervous system. In the group of examined newborn infants with hypoxic ischemic lesions, from 149 children 1 (0.67% died, 87 (53.89% had normal findings, whereas the handicap was established in 61 (40.94%. Perinatal asphyxia affects the fetus and newborn infants not by individual factors, but with at least three or four associated factors. The disorders caused by asphyxia are in inverse proportion to the duration and intensity of hypoxic insults and the gestational age of the newborn. .

  20. The Interplay of Maternal Sensitivity and Gentle Control When Predicting Children's Subsequent Academic Functioning: Evidence of Mediation by Effortful Control

    Science.gov (United States)

    Kopystynska, Olena; Spinrad, Tracy L.; Seay, Danielle M.; Eisenberg, Nancy

    2016-01-01

    The goal of this work was to examine the complex interrelation of mothers' early gentle control and sensitivity in predicting children's effortful control (EC) and academic functioning. Maternal gentle control, maternal sensitivity, and children's EC were measured when children were 18, 30, and 42 months of age (T1, T2, and T3, respectively), and…

  1. Hypoxic challenge test applied to healthy children

    DEFF Research Database (Denmark)

    Kobbernagel, Helene Elgaard; Nielsen, Kim Gjerum; Hanel, Birgitte

    2013-01-01

    BACKGROUND: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised if...

  2. Hypoxic conditioning as a new therapeutic modality

    Directory of Open Access Journals (Sweden)

    Samuel eVerges

    2015-06-01

    Full Text Available Preconditioning refers to a procedure by which a single noxious stimulus below the threshold of damage is applied to the tissue in order to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic preconditioning relies on complex and active defenses that organisms have developed to counter the adverse consequences of oxygen deprivation. The protection it confers against ischemic attack for instance as well as the underlying biological mechanisms have been extensively investigated in animal models. Based on these data, hypoxic conditioning (consisting in recurrent exposure to hypoxia has been suggested a potential non-pharmacological therapeutic intervention to enhance some physiological functions in individuals in whom acute or chronic pathological events are anticipated or existing. In addition to healthy subjects, some benefits have been reported in patients with cardiovascular and pulmonary diseases as well as in overweight and obese individuals. Hypoxic conditioning consisting in sessions of intermittent exposure to moderate hypoxia repeated over several weeks may induce hematological, vascular, metabolic and neurological effects. This review addresses the existing evidence regarding the use of hypoxic conditioning as a potential therapeutic modality and emphasizes on many remaining issues to clarify and future researches to be performed in the field.

  3. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  4. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  5. Tracking Hypoxic Signaling within Encapsulated Cell Aggregates

    Science.gov (United States)

    Skiles, Matthew L.; Sahai, Suchit; Blanchette, James O.

    2011-01-01

    nutrients, notably oxygen, is therefore reduced and limited by diffusion. This reduced oxygen availability may especially impact β-cells whose insulin secretory function is highly dependent on oxygen11-13. Capsule composition and geometry will also impact diffusion rates and lengths for oxygen. Therefore, we also describe a technique for identifying hypoxic cells within our PEG capsules. Infection of the cells with a recombinant adenovirus allows for a fluorescent signal to be produced when intracellular hypoxia-inducible factor (HIF) pathways are activated14. As HIFs are the primary regulators of the transcriptional response to hypoxia, they represent an ideal target marker for detection of hypoxic signaling15. This approach allows for easy and rapid detection of hypoxic cells. Briefly, the adenovirus has the sequence for a red fluorescent protein (Ds Red DR from Clontech) under the control of a hypoxia-responsive element (HRE) trimer. Stabilization of HIF-1 by low oxygen conditions will drive transcription of the fluorescent protein (Figure 1). Additional details on the construction of this virus have been published previously15. The virus is stored in 10% glycerol at -80° C as many 150 μL aliquots in 1.5 mL centrifuge tubes at a concentration of 3.4 x 1010 pfu/mL. Previous studies in our lab have shown that MIN6 cells encapsulated as aggregates maintain their viability throughout 4 weeks of culture in 20% oxygen. MIN6 aggregates cultured at 2 or 1% oxygen showed both signs of necrotic cells (still about 85-90% viable) by staining with ethidium bromide as well as morphological changes relative to cells in 20% oxygen. The smooth spherical shape of the aggregates displayed at 20% was lost and aggregates appeared more like disorganized groups of cells. While the low oxygen stress does not cause a pronounced drop in viability, it is clearly impacting MIN6 aggregation and function as measured by glucose-stimulated insulin secretion15. Western blot analysis of encapsulated

  6. Tracking hypoxic signaling within encapsulated cell aggregates.

    Science.gov (United States)

    Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

    2011-12-16

    , is therefore reduced and limited by diffusion. This reduced oxygen availability may especially impact β-cells whose insulin secretory function is highly dependent on oxygen. Capsule composition and geometry will also impact diffusion rates and lengths for oxygen. Therefore, we also describe a technique for identifying hypoxic cells within our PEG capsules. Infection of the cells with a recombinant adenovirus allows for a fluorescent signal to be produced when intracellular hypoxia-inducible factor (HIF) pathways are activated. As HIFs are the primary regulators of the transcriptional response to hypoxia, they represent an ideal target marker for detection of hypoxic signaling. This approach allows for easy and rapid detection of hypoxic cells. Briefly, the adenovirus has the sequence for a red fluorescent protein (Ds Red DR from Clontech) under the control of a hypoxia-responsive element (HRE) trimer. Stabilization of HIF-1 by low oxygen conditions will drive transcription of the fluorescent protein (Figure 1). Additional details on the construction of this virus have been published previously. The virus is stored in 10% glycerol at -80° C as many 150 μL aliquots in 1.5 mL centrifuge tubes at a concentration of 3.4 x 10(10) pfu/mL. Previous studies in our lab have shown that MIN6 cells encapsulated as aggregates maintain their viability throughout 4 weeks of culture in 20% oxygen. MIN6 aggregates cultured at 2 or 1% oxygen showed both signs of necrotic cells (still about 85-90% viable) by staining with ethidium bromide as well as morphological changes relative to cells in 20% oxygen. The smooth spherical shape of the aggregates displayed at 20% was lost and aggregates appeared more like disorganized groups of cells. While the low oxygen stress does not cause a pronounced drop in viability, it is clearly impacting MIN6 aggregation and function as measured by glucose-stimulated insulin secretion. Western blot analysis of encapsulated cells in 20% and 1% oxygen also

  7. Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro-oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic challenges.

    Science.gov (United States)

    Ullah, Mohammad F; Ahmad, Aamir; Bhat, Showket H; Khan, Husain Y; Zubair, Haseeb; Sarkar, Fazlul H; Hadi, Sheikh M

    2016-04-01

    This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro-environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti-proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper-dependant pathway in which endogenous copper is mobilized by daidzein and redox-cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens.

  8. Effects of minocycline on learning and memory of mice following ischemic-hypoxic cerebral injuries

    Institute of Scientific and Technical Information of China (English)

    Hongling Fan; Yuanyin Zheng; Lijuan Xu; Zhichao Zhong; Shining Cai; Shuling Zhang; Quanzhong Chang

    2012-01-01

    An ischemic-hypoxic animal model was established using right common carotid artery occlusions and inhalation of low concentrations of oxygen in mice. At 10 days after the ischemic-hypoxic injuries, saline-treated mice exhibited significantly prolonged escape latencies in water-maze tests and significantly shorter memory latencies and more mistakes in step-down tests. In contrast, mice treated with 5 mg/kg minocycline exhibited significant reversals of each of these effects compared with the saline-treated control mice. Moreover, we found that minocycline can relieve brain water content and morphological changes in mice following ischemic-hypoxic cerebral injuries. Accordingly, our findings indicate that minocycline provides some protections against the deleterious effects of these injuries in mice.

  9. Blood immunological parameters upon hypoxic-ischemic injuries of central nervous system in newborns and infants

    Directory of Open Access Journals (Sweden)

    Gulomjan Khalimbetov

    2012-05-01

    Full Text Available The paper studies interrelation between immune system condition and circulating concentrations of neuropeptides and neuron-specific enolase (NSE upon perinatal pathology in newborns and infants. Reactivity of cytokine and interleukin links of immune systems was found varying in newborns and infants with CNS hypoxic-ischemic pathology, accompanied by psychomotor retardation, a psycho-speech disorder, emotional and behavioral disorders (EBD and paroxysmal syndrome. At admission irrespectively of a syndrome type in the patients with CNS hypoxic-ischemic pathology, as compared with the patients in the control group, circulating TNF-α and IL-1 were found increased by 3.4-4.1 and 6.4-7.9 times, respectively. Release of S100 protein and NSE seems to be the underlying mechanism for enhancement of synthesis and/or release of TNF-α and IL-1 into circulation of patients with CNS hypoxic-ischemic pathology.

  10. A weighted mixed-sensitivity H-infinity-control design for irrational transfer matrices

    NARCIS (Netherlands)

    Curtain, RF; Zhou, YS

    1996-01-01

    Approximate solutions to a weighted mixed-sensitivity H-x-control problem for an irrational transfer matrix are obtained by solving the same problem for a reduced-order (rational) transfer matrix. Upper and lower bounds for the sensitivity are obtained in terms of the sensitivity for the reduced-ord

  11. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes

    Science.gov (United States)

    Canetti, G.; Fox, Wallace; Khomenko, A.; Mahler, H. T.; Menon, N. K.; Mitchison, D. A.; Rist, N.; Šmelev, N. A.

    1969-01-01

    In a paper arising out of an informal international consultation of specialists in the bacteriology of tuberculosis held in 1961, an attempt was made to formulate criteria, and specify technical procedures, for reliable tests of sensitivity (the absolute-concentration method, the resistance-ratio method and the proportion method) to the 3 main antituberculosis drugs (isoniazid, streptomycin and p-aminosalicylic acid). Seven years later, a further consultation was held to review the latest developments in the field and to suggest how sensitivity tests might be put to practical use in tuberculosis control programmes. The participants reached agreement on how to define drug sensitivity and resistance, and stressed the importance of using a discrimination approach to the calibration of sensitivity tests. Their views are contained in the present paper, which also includes descriptions of the sensitivity tests used by the Medical Research Council of Great Britain for first- and second-line drugs (minimal inhibitory concentration and resistance-ratio methods), the two main variants of the proportion method developed by the Institut Pasteur, Paris, and a method for calibrating sensitivity tests. PMID:5309084

  12. Stability and Sensitivity Analysis of Fuzzy Control Systems. Mechatronics Applications

    OpenAIRE

    Radu-Emil Precup; Stefan Preitl

    2006-01-01

    The development of fuzzy control systems is usually performed by heuristicmeans, incorporating human skills, the drawback being in the lack of general-purposedevelopment methods. A major problem, which follows from this development, is theanalysis of the structural properties of the control system, such as stability, controllabilityand robustness. Here comes the first goal of the paper, to present a stability analysismethod dedicated to fuzzy control systems with mechatronics applications bas...

  13. Efffect of Aeroallergen Sensitization on Asthma Control in African-American Teens with Persistent Asthma

    Science.gov (United States)

    In African-American adolescents with persistent asthma, allergic profile predicted the likelihood of having poorly controlled asthma despite guidelines-directed therapies. Our results suggest that tree and weed pollen sensitization are independent risk factors for poorly controll...

  14. Reward and punishment sensitivity and alcohol use: the moderating role of executive control.

    Science.gov (United States)

    Jonker, Nienke C; Ostafin, Brian D; Glashouwer, Klaske A; van Hemel-Ruiter, Madelon E; de Jong, Peter J

    2014-05-01

    Reward sensitivity and to a lesser extent punishment sensitivity have been found to explain individual differences in alcohol use. Furthermore, many studies showed that addictive behaviors are characterized by impaired self-regulatory processes, and that individual differences related to alcohol use are moderated by executive control. This is the first study that explores the potential moderating role of executive control in the relation between reward and punishment sensitivity and alcohol use. Participants were 76 university students, selected on earlier given information about their alcohol use. Half of the participants indicated to drink little alcohol and half indicated to drink substantial amounts of alcohol. As expected, correlational analyses showed a positive relationship between reward sensitivity and alcohol use and a negative relation between punishment sensitivity and alcohol use. Regression analysis confirmed that reward sensitivity was a significant independent predictor of alcohol use. Executive control moderated the relation between punishment sensitivity and alcohol use, but not the relation between reward sensitivity and alcohol use. Only in individuals with weak executive control punishment sensitivity and alcohol use were negatively related. The results suggest that for individuals with weak executive control, punishment sensitivity might be a protective factor working against substantial alcohol use.

  15. Hypoxia monitoring activities within the FP7 EU-project HYPOX: diverse approaches to understand a complex phenomenon

    Science.gov (United States)

    Janssen, F.; Waldmann, C.; Boetius, A.

    2012-04-01

    Hypoxic conditions in aquatic systems and the occurrence of 'dead zones' increase worldwide due to man-made eutrophication and global warming with consequences for biodiversity, ecosystem functions and services such as fisheries, aquaculture and tourism. Monitoring of hypoxia and its consequences has to (1) account for the appropriate temporal and spatial scales, (2) separate anthropogenic from natural drivers and long-term trends from natural variations, (3) assess ecosystem response, (4) use modeling tools for generalization and prediction, and (5) share data and obtained knowledge. In 2009 the EU FP7 project HYPOX (www.hypox.net) started out as a pioneering attempt to improve and integrate hypoxia observation capacities addressing these requirements. Target ecosystems selected for HYPOX cover a broad range of settings (e.g., hydrography, oxygenation status, biological activity, anthropogenic impact) and differ in their sensitivity towards change. Semi-enclosed basins with permanent anoxia (Black Sea, Baltic Sea), are included as well as seasonally or locally hypoxic land-locked systems (fjords, lagoons, lakes) and open ocean systems with high sensitivity to global warming (North Atlantic - Arctic transition). Adopted monitoring approaches involve autonomous, cabled, and shipboard instruments and include static and profiling moorings, benthic observatories, drifters, as well as classical CTD surveys. In order to improve observatory performance, project activities encompass developments of oxygen sensors as well as calibration procedures and technologies to reduce biofouling. Modeling and data assimilation are used to synthesize findings, to obtain an in-depth understanding of hypoxia causes and consequences, and to improve forecasting capacities. For integration of the collected information into a global oxygen observing system, results are disseminated through the HYPOX portal following GEOSS data sharing principles. This presentation will give an overview of

  16. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues.

    Science.gov (United States)

    Wiebe, L I; Stypinski, D

    1996-09-01

    Although hypoxia has been known for decades to play an important role in the outcome of radiotherapy in oncology, and inspite of the contribution of hypoxia to a myriad of pathologies that involve vascular disease, the selective imaging of hypoxic tissue has attained prominence only within the past decade. Contemporary research in the hypoxia imaging field is based largely on radiosensitizer research of the 1960's and 1970's. Early sensitizer research identified a family of nitro-organic compounds, the N-1 substituted 2-nitroimidazoles as candidate drugs. The early champion, and still the reference standard for therapeutic radiosensitization of hypoxic tumor cells is misonidazole (MISO). Its peripheral neurotoxicity led to failure in clinical studies, but its biological, biophysical and biochemical properties have been investigated in detail and serve as a basis for further design, not only of sensitizers, but of diagnostic radiopharmaceuticals for imaging tissue hypoxia. Pharmacokinetic characterization of radiopharmaceuticals, specifically radiopharmaceuticals for imaging tissue hypoxia, has not been a central theme in their development. The advent of PET, through which quantitative determinations first became possible, opened the field for both descriptive and analytical radiopharmacokinetic studies. In SPECT, however, this approach is still undergoing refinement. This paper addresses some of the underlying issues in radiopharmaceutical pharmacokinetics. There is a paucity of published radiopharmacokinetic data for SPECT hypoxia imaging agents. Consequently, the pharmacokinetic issues for MISO are presented as a basis for development of pharmacokinetics for the chemically-related imaging agents. Properties of an hypoxia marker are described from a pharmacokinetic viewpoint, a theoretical model for descriptive pharmacokinetics is introduced and finally, recent pharmacokinetic studies from our laboratory are described.

  17. Chemoreceptor stimulation and hypoxic pulmonary vasoconstriction in conscious dogs.

    Science.gov (United States)

    Levitzky, M G

    1979-07-01

    Dogs with electromagnetic flow probes implanted on their left (QL) and main (QT) pulmonary arteries, catheters in their left atria and external jugular veins, and chronic tracheostomies were trained to accept Carlens dual-lumen endotracheal tubes into their tracheostomies, thus allowing separate ventilation of the two lungs. Swan-Ganz catheters were inserted through the jugular vein catheters. Pneumotachographs measured air flow to each lung. During bilateral ventilation with room air or O2, QL was about 36% of QT. When the left lung was ventilated with N2 while the right remained on O2, PAO2 was above 90 mmHg and QL fell to about 25% of QT. When the left lung was ventilated with N2 and the right with room air, PAO2 fell below 40 mm Hg and QL increased to control levels. This increase in perfusion of the hypoxic lung during systemic hypoxemia was not seen in dogs after surgical deafferentation of the systemic arterial chemoreceptors, indicating that stimulation of the arterial chemoreceptors may interfere with the hypoxic pulmonary vasoconstriction.

  18. A RISK-SENSITIVE STOCHASTIC MAXIMUM PRINCIPLE FOR OPTIMAL CONTROL OF JUMP DIFFUSIONS AND ITS APPLICATIONS

    Institute of Scientific and Technical Information of China (English)

    Shi Jingtao; Wu Zhen

    2011-01-01

    A stochastic maximum principle for the risk-sensitive optimal control prob- lem of jump diffusion processes with an exponential-of-integral cost functional is derived assuming that the value function is smooth, where the diffusion and jump term may both depend on the control. The form of the maximum principle is similar to its risk-neutral counterpart. But the adjoint equations and the maximum condition heavily depend on the risk-sensitive parameter. As applications, a linear-quadratic risk-sensitive control problem is solved by using the maximum principle derived and explicit optimal control is obtained.

  19. Parametric sensitivity analysis for temperature control in outdoor photobioreactors.

    Science.gov (United States)

    Pereira, Darlan A; Rodrigues, Vinicius O; Gómez, Sonia V; Sales, Emerson A; Jorquera, Orlando

    2013-09-01

    In this study a critical analysis of input parameters on a model to describe the broth temperature in flat plate photobioreactors throughout the day is carried out in order to assess the effect of these parameters on the model. Using the design of experiment approach, variation of selected parameters was introduced and the influence of each parameter on the broth temperature was evaluated by a parametric sensitivity analysis. The results show that the major influence on the broth temperature is that from the reactor wall and the shading factor, both related to the direct and reflected solar irradiation. Other parameter which play an important role on the temperature is the distance between plates. This study provides information to improve the design and establish the most appropriate operating conditions for the cultivation of microalgae in outdoor systems.

  20. Inhaled lead affects lung pathology and inflammation in sensitized and control guinea pigs.

    Science.gov (United States)

    Boskabady, Mohammad Hossein; Tabatabai, Sayed Abas; Farkhondeh, Tahereh

    2016-04-01

    The association between lead exposure and respiratory diseases including asthma is controversial. Some studies indicate that exposure to environmental lead pollution may cause asthma; however, there is not sufficient data in this regard. The effect of lead on lung pathological findings and serum inflammatory mediators in sensitized and non-sensitized guinea pigs exposed to inhaled lead was examined. Eleven animal groups including control, sensitized, three groups of non sensitized animals, three groups during sensitization, and three groups after sensitization exposed to aerosol of three lead concentrations (n = 6 for each group) were studied. Serum inflammatory mediators levels and lung pathological changes were evaluated. All pathological changes and serum ET-1, EPO, NO levels were significantly higher in the sensitized and non sensitized animals exposed to lead than control group (p lead concentration and sensitized group. Serum inflammatory mediators levels and pathological findings in sensitized groups exposed to lead both during and after sensitization were significantly higher than sensitized non exposed group (p lead concentration were significantly higher than those of medium and low concentrations; those of medium concentration were also higher than low concentration (p lead is able to induce respiratory changes similar to asthma. In addition, the results indicated that exposure to environmental lead is able to aggravate asthma severity both during development of asthma or after its manifestation.

  1. Directional sensitivity of "first trial" reactions in human balance control.

    NARCIS (Netherlands)

    Oude Nijhuis, L.B.; Allum, J.H.J.; Borm, G.F.; Honegger, F.; Overeem, S.; Bloem, B.R.

    2009-01-01

    Support-surface movements are commonly used to examine balance control. Subjects typically receive a series of identical or randomly interspersed multidirectional balance perturbations and the atypical "first trial reaction" (evoked by the first perturbation) is often excluded from further analysis.

  2. Sensitivity analysis of a pharmaceutical tablet production process from the control engineering perspective.

    Science.gov (United States)

    Rehrl, Jakob; Gruber, Arlin; Khinast, Johannes G; Horn, Martin

    2017-01-30

    This paper presents a sensitivity analysis of a pharmaceutical direct compaction process. Sensitivity analysis is an important tool for gaining valuable process insights and designing a process control concept. Examining its results in a systematic manner makes it possible to assign actuating signals to controlled variables. This paper presents mathematical models for individual unit operations, on which the sensitivity analysis is based. Two sensitivity analysis methods are outlined: (i) based on the so-called Sobol indices and (ii) based on the steady-state gains and the frequency response of the proposed plant model.

  3. Risk-Sensitive Control of Pure Jump Process on Countable Space with Near Monotone Cost

    Energy Technology Data Exchange (ETDEWEB)

    Suresh Kumar, K., E-mail: suresh@math.iitb.ac.in; Pal, Chandan, E-mail: cpal@math.iitb.ac.in [Indian Institute of Technology Bombay, Department of Mathematics (India)

    2013-12-15

    In this article, we study risk-sensitive control problem with controlled continuous time pure jump process on a countable space as state dynamics. We prove multiplicative dynamic programming principle, elliptic and parabolic Harnack’s inequalities. Using the multiplicative dynamic programing principle and the Harnack’s inequalities, we prove the existence and a characterization of optimal risk-sensitive control under the near monotone condition.

  4. Alcohol Sensitivity Moderates the Indirect Associations between Impulsive Traits, Impaired Control over Drinking, and Drinking Outcomes

    Science.gov (United States)

    Wardell, Jeffrey D.; Quilty, Lena C.; Hendershot, Christian S.

    2017-01-01

    Objective To examine impaired control over drinking behavior as a mediator of unique pathways from impulsive traits to alcohol outcomes in young adults and to investigate the moderating influence of self-reported sensitivity to alcohol on these pathways. Method Young adult heavy drinkers (N=172; n=82 women) recruited from the community completed self-report measures of impulsive traits (positive urgency, negative urgency, sensation seeking), alcohol sensitivity (Self-Rating of the Effects of Alcohol scale), impaired control over drinking, and alcohol use and problems. Multiple-groups path analysis was used to analyze the data. Results Path coefficients between urgency and impaired control were larger for individuals with lower versus higher self-reported sensitivity to alcohol. The same was true for the association between impaired control and alcohol problems. For participants lower on alcohol sensitivity, significant indirect paths were observed from both positive and negative urgency to all alcohol outcomes (quantity, frequency, and problems) mediated via impaired control. For participants higher on alcohol sensitivity, only the paths from negative urgency (but not positive urgency) to the three alcohol outcomes via impaired control were statistically significant. Sensation seeking was not uniquely associated with impaired control. Conclusions The findings indicate that relatively low sensitivity to the pharmacological effects of alcohol may exacerbate the association of urgency – especially positive urgency – with impaired control, supporting the notion that personality and level of response to alcohol may interact to increase risk for impaired control over drinking. PMID:25785803

  5. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2016-08-05

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC

  6. A space vector control stradegy for improvement of control speed and reduction of sensitivity of phase jump

    DEFF Research Database (Denmark)

    Rasmussen, Tonny Wederberg

    1999-01-01

    The paper describes a full space vector control stradegy. The synchronisation used to improveboth the control speed of reactive power and reduce the sensitivity to large phase jumps in the grid caused by switching arge loads. The control stradegy is tested with a 5-level 10kvar laboratory model....

  7. Post-metabolic response to passive normobaric hypoxic exposure in sedendary overweight males: a pilot study

    Directory of Open Access Journals (Sweden)

    Workman Chad

    2012-11-01

    Full Text Available Abstract Background The present pilot study was designed to test the impact of passive acute normobaric hypoxic exposure (PAH and passive short-term normobaric hypoxic exposure (PSH conditions on energy expenditure (EE and substrates utilisation (glucose and lipid oxidation. Methods Eleven participants have completed the PAH session while the control group (CG underwent a simulated experimental condition in normobaric normoxic condition. A subset of 6 participants underwent an additional six 3-hour sessions on consecutive days. Metabolic rates were obtained pre- and post-treatments on the morning following an overnight (12 hours fast in PAH, PSH, and CG groups. Results The statistical outcomes showed a significant increase in EE for PAH, control, and PSH while a shift in substrate utilization towards lipid sources was only detected for PAH and PSH, respectively. Conclusion This pilot study showed that passive acute normobaric hypoxic exposure did affect EE and fuel utilization in sedentary overweight males and that further passive normobaric hypoxic exposures (PSH magnified these metabolic adjustments. These outcomes provide valuable information for further research in the area of hypoxia as a new therapeutic strategy to improve the management of weight loss.

  8. Directional sensitivity of "first trial" reactions in human balance control.

    Science.gov (United States)

    Oude Nijhuis, Lars B; Allum, John H J; Borm, George F; Honegger, Flurin; Overeem, Sebastiaan; Bloem, Bastiaan R

    2009-06-01

    Support-surface movements are commonly used to examine balance control. Subjects typically receive a series of identical or randomly interspersed multidirectional balance perturbations and the atypical "first trial reaction" (evoked by the first perturbation) is often excluded from further analysis. However, this procedure may obscure vital information about neurophysiological mechanisms associated with the first perturbation and, by analogy, fully unexpected falls. We studied first trial reactions, aiming to clarify their directional impact on postural control and to characterize the underlying neurophysiological substrate. We instructed 36 subjects to maintain balance following support-surface rotations in six different directions. Perturbations in each direction were delivered in blocks, consisting of 10 serial stimuli. Full body kinematics, surface reactive forces, and electromyographic (EMG) responses were recorded. Regardless of direction, for the very first rotation, displacement of the center of mass was 15% larger compared with the ensuing nine identical rotations (P postural instability, mainly due to increased response amplitudes. Although rapid habituation occurs following presentation of identical stimuli, subjects immediately become unstable again when the perturbation direction suddenly changes. Excessive responses due to a failure to combine proprioceptive and vestibular cues effectively may explain this instability seen with first trials, particularly when falling backward.

  9. Sensitivity analysis of Lyapunov and Riccati equations with application to controls-structures integrated design

    Science.gov (United States)

    Hou, Gene; Koganti, Gopichand

    1993-01-01

    Controls-structure integrated design is a complicated multidisciplinary design optimization problem which involves the state equations pertaining to open-loop eigenvalues and control laws. In order to alleviate the intensity of the computation, this study uses the adjoint variable method to derive sensitivity equations for the eigenvalue, Liapunov, and Riccati equations. These individual sensitivity equations are then combined together to form the multidisciplinary sensitivity equations for the control structure integrated design problems. A set of linear sensitivity equations, proportional in number to the number of performance functions involved in the optimization process, are solved. This proposed approach may provide a great saving in computer resources. The validity of the newly developed sensitivity equations is verified by numerical examples.

  10. Lycopene control of benzophenone-sensitized lipid peroxidation

    Science.gov (United States)

    Cvetković, Dragan; Marković, Dejan

    2012-05-01

    Lycopene antioxidant activity in the presence of two different mixtures of phospholipids in hexane solution, under continuous regime of UV-irradiation from three different ranges (UV-A, UV-B, and UV-C) has been evaluated in this work. Lycopene expected role was to control lipid peroxidation, by scavenging free radicals generated by UV-irradiation, in the presence and in the absence of selected photosensitizer, benzophenone. This work shows that lycopene undergoes to UV-induced destruction (bleaching), highly dependent on the incident photons energy input, more expressed in the presence than in the absence of benzophenone. The further increase ("excess") of its bleaching is undoubtedly related to the further increase of its antioxidant activity in the presence of benzophenone, having the same cause: increase of (phospholipids peroxidation) chain-breaking activities.

  11. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress

    Science.gov (United States)

    Bassi, C; Ho, J; Srikumar, T; Dowling, RJO; Gorrini, C; Miller, SJ; Mak, TW; Neel, BG; Raught, B; Stambolic, V

    2016-01-01

    Loss of function of the Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene is associated with many human cancers. In the cytoplasm, PTEN antagonizes the Phosphatidylinositol 3′ kinase (PI3K) signaling pathway. PTEN also accumulates in the nucleus, where its function remains poorly understood. We demonstrate that SUMOylation (SUMO) of PTEN controls its nuclear localization. In cells exposed to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus dependent on the protein kinase Ataxia telangiectasia mutated (ATM). Cells lacking nuclear PTEN were hypersensitive to DNA damage, while PTEN-deficient cells were susceptible to killing by a combination of genotoxic stress and a small molecule PI3K inhibitor both in vitro and in vivo. Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors. PMID:23888040

  12. Girls' Rumination and Anxiety Sensitivity: Are They Related after Controlling for Girl, Maternal, and Parenting Factors?

    Science.gov (United States)

    Gardner, Christie; Epkins, Catherine C.

    2012-01-01

    Background: Rumination and anxiety sensitivity are posited cognitive vulnerabilities in the development and/or maintenance of depression and anxiety and have only been examined separately in youth. Objective: We examined the relation between rumination and anxiety sensitivity in girls, after controlling for other girl, maternal, and parenting…

  13. Simultaneous recording of ATP-sensitive K+ current and intracellular Ca2+ in anoxic rat ventricular myocytes. Effects of glibenclamide.

    Science.gov (United States)

    Russ, U; Englert, H; Schölkens, B A; Gögelein, H

    1996-05-01

    We investigated the temporal relationship between the adenosine triphosphate-sensitive K current (KATP current), hypoxic shortening and Ca accumulation in cardiomyocytes exposed to anoxia or metabolic inhibition. Whole-cell, patch-clamp experiments were performed with nonstimulated isolated rat heart ventricular muscle cells loaded with the Ca-sensitive fluorescent dye 1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'- amino-5'-methylphenoxy) ethane-N,N,N',N'-tetraacetic acid (fura-2) via the patch pipette. After approximately 8 min anoxia, the KATP current started to rise and reached a maximum of 21.3 +/- 3.7 nA (n = 5, recorded at 0 mV clamp potential) within 1-3 min. At that time hypoxic contracture also occurred. Resting cytoplasmic free calcium (Cai) did not change significantly before hypoxic shortening. After hypoxic contracture, the KATP current decreased and Cai started to rise, reaching about 1 micromol/l. The presence of glibenclamide (10 micromol/l) in the bath reduced the anoxia-induced KATP current by more than 50%, but did not significantly influence the time dependence of current, hypoxic shortening and Cai, or the magnitude of Cai. Metabolic inhibition with 1.5 mmol/l CN resulted in KATP current increase and hypoxic shortening, occurring somewhat earlier than under anoxia, but all other parameters were comparable. In non-patch-clamped cells loaded with fura-2 AM ester and field-stimulated with 1 Hz, 1 micronol/l glibenclamide had no significant effect on the magnitude of the Cai increase caused by exposure of the cells to 1.5 mmol/l CN-. After CN- wash-out in non-patch-clamped cells, Cai declined, oscillated and finally returned to control values. It can be concluded that glibenclamide inhibits anoxia-induced KATP currents only partially and has no significant effect on anoxia-induced rise in resting Cai.

  14. Sensitivity to plant modelling uncertainties in optimal feedback control of sound radiation from a panel

    DEFF Research Database (Denmark)

    Mørkholt, Jakob

    1997-01-01

    Optimal feedback control of broadband sound radiation from a rectangular baffled panel has been investigated through computer simulations. Special emphasis has been put on the sensitivity of the optimal feedback control to uncertainties in the modelling of the system under control.A model of a re...

  15. Enhanced hypoxic pulmonary vasoconstriction in hypertension.

    Science.gov (United States)

    Guazzi, M D; Alimento, M; Berti, M; Fiorentini, C; Galli, C; Tamborini, G

    1989-02-01

    In this study, we tested the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension. The hypothesis took origin from the following two considerations: alveolar hypoxia constricts the pulmonary vessels by enhancing the Ca2+ penetration across sarcolemma of the smooth muscle cells and systemic high blood pressure is associated with an elevation of tone and reactivity of the lung vessels, which seems to depend on an excessive cytosol free Ca2+ concentration due to alterations in sodium handling and in the Na+-Ca2+ exchange system. These considerations suggest the possibility that the disorders in the biochemistry of smooth muscle contraction in hypertension facilitate the rise of cytosol Ca2+ concentration during alveolar hypoxia, thus resulting in a potentiation of the vasoconstrictor properties of this stimulus. In 43 hypertensive and 17 normotensive men, pulmonary arteriolar resistance has been evaluated during air respiration and after 15 minutes of breathing 17%, 15%, and 12% oxygen in nitrogen. Curves relating changes in pulmonary arteriolar resistance to oxygen breathing contents had similar configuration in the two populations but in hypertension were steeper and significantly shifted to the left, reflecting a lower threshold and an enhanced reactivity. This pattern was not related to differences in severity of the hypoxic stimulus, plasma catecholamine concentration, or hypocapnia and respiratory alkalosis induced by hypoxia and probably was not mediated through alpha-receptor activation. Calcium channel blockade with nifedipine was able to almost abolish both the normotensive and the hypertensive pulmonary vasoconstriction reaction. These findings support the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension.

  16. Method of controlled reduction of nitroaromatics by enzymatic reaction with oxygen sensitive nitroreductase enzymes

    Science.gov (United States)

    Shah, Manish M.; Campbell, James A.

    1998-01-01

    A method for the controlled reduction of nitroaromatic compounds such as nitrobenzene and 2,4,6-trinitrotoluene by enzymatic reaction with oxygen sensitive nitroreductase enzymes, such as ferredoxin NADP oxidoreductase.

  17. Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior : A Longitudinal TRAILS Study

    NARCIS (Netherlands)

    Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

    2017-01-01

    Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents' risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this

  18. Loss Performance Modeling for Hierarchical Heterogeneous Wireless Networks With Speed-Sensitive Call Admission Control

    DEFF Research Database (Denmark)

    Huang, Qian; Huang, Yue-Cai; Ko, King-Tim;

    2011-01-01

    dimensioning and planning. This paper investigates the computationally efficient loss performance modeling for multiservice in hierarchical heterogeneous wireless networks. A speed-sensitive call admission control (CAC) scheme is considered in our model to assign overflowed calls to appropriate tiers...

  19. Conformational control of benzophenone-sensitized charge transfer in dinucleotides.

    Science.gov (United States)

    Merz, Thomas; Wenninger, Matthias; Weinberger, Michael; Riedle, Eberhard; Wagenknecht, Hans-Achim; Schütz, Martin

    2013-11-14

    Charge transfer in DNA cannot be understood without addressing the complex conformational flexibility, which occurs on a wide range of timescales. In order to reduce this complexity four dinucleotide models 1X consisting of benzophenone linked by a phosphodiester to one of the natural nucleosides X = A, G, T, C were studied in water and methanol. The theoretical work focuses on the dynamics and electronic structure of 1G. Predominant conformations in the two solvents were obtained by molecular dynamics simulations. 1G in MeOH adopts mainly an open geometry with a distance of 12–16 Å between the two aromatic parts. In H2O the two parts of 1G form primarily a stacked conformation yielding a distance of 5–6 Å. The low-lying excited states were investigated by electronic structure theory in a QM/MM environment for representative snapshots of the trajectories. Photo-induced intramolecular charge transfer in the S1 state occurs exclusively in the stacked conformation. Ultrafast transient absorption spectroscopy with 1X reveals fast charge transfer from S1 in both solvents with varying yields. Significant charge transfer from the T1 state is only found for the nucleobases with the lowest oxidation potential: in H2O, charge transfer occurs with 3.2 × 10(9) s(-1) for 1A and 6.0 × 10(9) s(-1) for 1G. The reorganization energy remains nearly unchanged going from MeOH to the more polar H2O. The electronic coupling is rather low even for the stacked conformation with H(AB) = 3 meV and explains the moderate charge transfer rates. The solvent controls the conformational distribution and therefore gates the charge transfer due to differences in distance and stacking.

  20. Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT/Enhancer Binding Proteins

    Science.gov (United States)

    2016-10-01

    2016.03.005. PMID: 26968249 Page !26 11. APPENDICES: Page !27 Original Articles C/EBPβ regulates sensitivity to bortezomib in prostate cancer ...2016) 152–161 ORIGINAL ARTICLE CCAAT/Enhancer binding protein β controls androgen- deprivation-induced senescence in prostate cancer cells DJ Barakat1, J...AWARD NUMBER: W81XWH-14-1-0209 TITLE: Regulating Prostate Cancer Sensitivity to Chemotherapy through Translational Control of CCAAT/Enhancer

  1. Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior: A Longitudinal TRAILS Study

    OpenAIRE

    Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

    2017-01-01

    Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents’ risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this study we tested whether the imbalance between behavioral control and reward sensitivity underlies risk taking behavior in adolescence, using a nationally representative longitudinal sample of 715 ad...

  2. Control of Pratylenchus brachyurus with Selected Nonfumigant Nematicides on a Tolerant and a Sensitive Soybean Cultivar.

    Science.gov (United States)

    Koenning, S R; Schmitt, D P

    1987-10-01

    A field study was conducted to evaluate soybean cultivar sensitivity to Pratylenchus brachyurus and selected nonfumigant nematicides for control of this nematode. 'Essex', a tolerant cultivar, yielded more than 'Forrest' , a sensitive cultivar, in an infested field. Plots treated with aldicarb, carbofuran, and fenamiphos had fewer nematodes 40 days after planting than nontreated plots. Plots planted with Forrest and treated with carbofuran had a greater yield than the untreated controls.

  3. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmanić Šamija, R. [Department of Pediatrics, University Hospital Split, Split (Croatia); Primorac, D. [School of Medicine Split, University of Split, Split (Croatia); Department of Pediatrics, School of Medicine, University of Osijek, Osijek (Croatia); Eberly College of Science, Penn State University, University Park, PA (United States); St. Catherine Speciality Hospital, Zabok (Croatia); Rešić, B. [School of Medicine Split, University of Split, Split (Croatia); Pavlov, V. [Department of Neonatology, University Hospital Split, Split (Croatia); Čapkun, V. [Department of Nuclear Medicine, University Hospital Split, Split (Croatia); Punda, H. [School of Medicine Split, University of Split, Split (Croatia); Lozić, B. [Department of Pediatrics, University Hospital Split, Split (Croatia); Zemunik, T. [Department of Medical Biology, School of Medicine Split, University of Split, Split (Croatia)

    2014-08-15

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  4. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Kuzmanić Šamija, R; Primorac, D; Rešić, B; Pavlov, V; Čapkun, V; Punda, H; Lozić, B; Zemunik, T

    2014-10-01

    The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  5. Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    R. Kuzmani? ?amija

    2014-10-01

    Full Text Available The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

  6. Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults.

    Science.gov (United States)

    Casey, Darren P; Treichler, David P; Ganger, Charles T; Schneider, Aaron C; Ueda, Kenichi

    2015-01-15

    We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide (NO) signaling. Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway. Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise, particularly in older adults. Thirteen young (25 ± 1 yr) and 12 older (64 ± 2 yr) adults performed rhythmic forearm exercise at 20% of maximum voluntary contraction during normoxia and hypoxia (∼80% O2 saturation); both before (control) and 3 h after beetroot juice (BR) consumption. Forearm vascular conductance (FVC; ml·min(-1)·100 mmHg(-1)) was calculated from forearm blood flow (ml/min) and blood pressure (mmHg). Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise (i.e., % increase compared with respective normoxic exercise trial). Plasma nitrite was determined from venous blood samples obtained before the control trials and each of the exercise trials (normoxia and hypoxia) after BR. Consumption of BR increased plasma nitrite in both young and older adults (P vasodilator response to hypoxic exercise was attenuated in older compared with young adults (3.8 ± 1.7% vs. 14.2 ± 1.2%, P vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P vasodilator response to hypoxic exercise in older but not young adults.

  7. Influence of Ginkgo Biloba extract on beta-secretase in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions

    Institute of Scientific and Technical Information of China (English)

    Xueneng Guan; Fuling Yan

    2008-01-01

    BACKGROUND: Preparation of Ginkgo leaf has been widely used to improve cognitive deficits and dementia, in particular in Alzheimer's disease patients. However, the precise mechanism of action of Ginkgo leaf remains unclear.OBJECTIVE: To explore the effect of Ginkgo Biloba extract (Egb761), Ginaton, on β-secretase expression in rat hippocampal neuronal cultures following chronic hypoxic and hypoglycemic conditions.DESIGN, TIME AND SETTNG: Completely by randomized, grouping study. The experiment was performed at the Laboratory of Molecular Imaging, Southeast University between August 2006 and August 2007.MATERIALS: A total of 128 Wistar rats aged 24 hours were selected, and hippocampal neurons were harvested for primary cultures.METHODS: On day 7, primary hippocampal neuronal cultures were treated with Egb761 (0, 25, 50, 100, 150, and 200 μ g/mL) under hypoxic/hypoglycemic or hypoglycemic culture conditions for 12, 24, and 36 hours, respectively. Hippocampal neurons cultured in primary culture medium served as control.MAIN OUTCOME MEASURES: Cell viability was assayed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT); fluorescence detection of β-secretase activity was performed; Western Blot was used to measure β -secretase expression.RESULTS: Cell viability under hypoxic/hypoglycemic or hypoglycemic culture conditions was significantly less than control cells (P 25 μ g/mL Egb761 induced greater cell viability (P 0.05). Α -secretase activity was increased after 12 hours in hypoxic/hypoglycemic culture (P 0.05). Β -secretase activity was greater after 12, 24, and 36 hours in hypoxic/hypoglycemic culture conditions, compared with control conditions (P < 0.05). Β-secretase activity was significantly decreased in neurons treated with Egb761 for 12, 24, or 36 hours, compared with the hypoxic/hypoglycemic group (P < 0.05).β-secretase protein expression was significantly up-regulated in neurons cultured in hypoxic/hypoglycemic conditions for

  8. Cable bacteria generate a firewall against euxinia in seasonally hypoxic basins

    OpenAIRE

    Seitaj, Dorina; Schauer, Regina; Sulu-Gambari, Fatimah; Hidalgo-Martinez, Silvia; Malkin, Sairah Y.; Burdorf, Laurine D. W.; Slomp, Caroline P.; Meysman, Filip J. R.

    2015-01-01

    Seasonal oxygen depletion (hypoxia) in coastal bottom waters can lead to the release and persistence of free sulfide (euxinia), which is highly detrimental to marine life. Although coastal hypoxia is relatively common, reports of euxinia are less frequent, which suggests that certain environmental controls can delay the onset of euxinia. However, these controls and their prevalence are poorly understood. Here we present field observations from a seasonally hypoxic marine basin (Grevelingen, T...

  9. Prediction of dissolved oxygen concentration in hypoxic river systems using support vector machine: a case study of Wen-Rui Tang River, China.

    Science.gov (United States)

    Ji, Xiaoliang; Shang, Xu; Dahlgren, Randy A; Zhang, Minghua

    2017-07-01

    Accurate quantification of dissolved oxygen (DO) is critically important for managing water resources and controlling pollution. Artificial intelligence (AI) models have been successfully applied for modeling DO content in aquatic ecosystems with limited data. However, the efficacy of these AI models in predicting DO levels in the hypoxic river systems having multiple pollution sources and complicated pollutants behaviors is unclear. Given this dilemma, we developed a promising AI model, known as support vector machine (SVM), to predict the DO concentration in a hypoxic river in southeastern China. Four different calibration models, specifically, multiple linear regression, back propagation neural network, general regression neural network, and SVM, were established, and their prediction accuracy was systemically investigated and compared. A total of 11 hydro-chemical variables were used as model inputs. These variables were measured bimonthly at eight sampling sites along the rural-suburban-urban portion of Wen-Rui Tang River from 2004 to 2008. The performances of the established models were assessed through the mean square error (MSE), determination coefficient (R (2)), and Nash-Sutcliffe (NS) model efficiency. The results indicated that the SVM model was superior to other models in predicting DO concentration in Wen-Rui Tang River. For SVM, the MSE, R (2), and NS values for the testing subset were 0.9416 mg/L, 0.8646, and 0.8763, respectively. Sensitivity analysis showed that ammonium-nitrogen was the most significant input variable of the proposal SVM model. Overall, these results demonstrated that the proposed SVM model can efficiently predict water quality, especially for highly impaired and hypoxic river systems.

  10. Motion and vibration control of a slewing flexible structure by SMA actuators and parameter sensitivity analysis

    Science.gov (United States)

    Janzen, F. C.; Tusset, A. M.; Piccirillo, V.; Balthazar, J. M.; Brasil, R. M. L. R. F.

    2015-11-01

    This work presents two approaches to the problem of vibration and positioning control of a flexible structural beam driven by a DC motor. The position is controlled by the current applied to the DC motor armature. A Shape Memory Alloy (SMA) actuator controls vibrations of the flexible structural beam. The State Dependent Riccati Equation (SDRE) technique is used to provide a control action which uses sub-optimal control and system local stability search. The robustness of these two controllers is tested by sensitivity analysis to parametric uncertainties. Numerical simulations results are presented to demonstrate the effectiveness of the proposed control strategy.

  11. Hypoxic preconditioning in an autohypoxic animal model

    Institute of Scientific and Technical Information of China (English)

    Guo Shao; Guo-Wei Lu

    2012-01-01

    Hypoxic preconditioning refers to the exposure of organisms,systems,organs,tissues or cells to moderate hypoxia/ischemia that [Results]in increased resistance to a subsequent episode of severe hypoxia/ischemia.In this article,we review recent research based on a mouse model of repeated exposure to autohypoxia.Pre-exposure markedly increases the tolerance to or protection against hypoxic insult,and preserves the cellular structure of the brain.Furthermore,the hippocampal activity amplitude and frequency of electroencephalogram,latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease,while spatial learning and memory improve.In the brain,detrimental neurochemicals such as free radicals are down-regulated,while beneficial ones such as adenosine are upregulated.Also,antihypoxia factor(s) and gene(s) are activated.We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades.A potential path for further research is the development of devices and pharmaceuticals acting on antihypoxia factor(s) and gene(s) for the prevention and treatment of hypoxia and related syndromes.

  12. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  13. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  14. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Science.gov (United States)

    Huang, Yuejun; Lai, Huihong; Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Chen, Yunbin; Ma, Lian

    2013-01-01

    In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  15. Radiation Sensitization in Cancer Therapy.

    Science.gov (United States)

    Greenstock, Clive L.

    1981-01-01

    Discusses various aspects of radiation damage to biological material, including free radical mechanisms, radiation sensitization and protection, tumor hypoxia, mechanism of hypoxic cell radiosensitization, redox model for radiation modification, sensitizer probes of cellular radiation targets, pulse radiolysis studies of free radical kinetics,…

  16. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Science.gov (United States)

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  17. Extreme hypoxic conditions induce selective molecular responses and metabolic reset in detached apple fruit

    Directory of Open Access Journals (Sweden)

    Dubravka eCukrov

    2016-02-01

    Full Text Available The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control and hypoxic (0.4 and 0.8 kPa oxygen conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1,000 genes differentially expressed when comparing 0.4 vs 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These

  18. Evidence of hypoxic foraging forays by yellow perch (Perca flavescens) and potential consequences for prey consumption

    Science.gov (United States)

    Roberts, James J.; Grecay, Paul A.; Ludsin, Stuart A.; Pothoven, Steve A.; Vanderploeg, Henry A.; Höök, Tomas O.

    2012-01-01

    Previous studies in a variety of ecosystems have shown that ecologically and economically important benthic and bentho-pelagic fishes avoid hypoxic (−1) habitats by moving vertically or horizontally to more oxygenated areas. While avoidance of hypoxic conditions generally leads to a complete shift away from preferred benthic prey, some individual fish continue to consume benthic prey items in spite of bottom hypoxia, suggesting complex habitat utilisation and foraging patterns. For example, Lake Erie yellow perch (Perca flavescens) continue to consume benthic prey, despite being displaced vertically and horizontally by hypolimnetic hypoxia. We hypothesised that hypolimnetic hypoxia can negatively affect yellow perch by altering their distribution and inducing energetically expensive foraging behaviour. To test this hypothesis, we used drifting hydroacoustics and trawl sampling to quantify water column distribution, sub-daily vertical movement and foraging behaviour of yellow perch within hypoxic and normoxic habitats of Lake Erie’s central basin during August-September 2007. We also investigated the effects of rapid changes in ambient oxygen conditions on yellow perch consumption potential by exposing yellow perch to various static and fluctuating oxygen conditions in a controlled laboratory experiment. Our results indicate that, while yellow perch in general avoid hypoxic conditions, some individuals undertake foraging forays into hypoxic habitats where they experience greater fluctuations in abiotic conditions (pressure, temperature and oxygen concentration) than at normoxic sites. However, laboratory results suggest short-term exposure to low oxygen conditions did not negatively impact consumption potential of yellow perch. Detailed understanding of sub-daily individual behaviours may be crucial for determining interactive individual- and ecosystem-level effects of stressors such as hypoxia.

  19. Voltage-Sensitive Load Controllers for Voltage Regulation and Increased Load Factor in Distribution Systems

    DEFF Research Database (Denmark)

    Douglass, Philip James; Garcia-Valle, Rodrigo; Østergaard, Jacob

    2014-01-01

    consumption which can be mapped to temperature setpoint offsets of thermostat controlled loads. In networks where a lower voltage level corresponds to high system load (and vice versa), this controller acts to regulate voltage and increase the load factor. Simulations are conducted on low- and medium-voltage......This paper presents a novel controller design for controlling appliances based on local measurements of voltage. The controller finds the normalized voltage deviation accounting for the sensitivity of voltage measurements to appliance state. The controller produces a signal indicating desired power...... distribution systems with residential loads including voltage-sensitive water heaters. In low-voltage systems, the results of the simulations show the controller to be effective at reducing the extremes of voltage and increasing the load factor while respecting end-use temperature constraints. In medium-voltage...

  20. North Pacific deglacial hypoxic events linked to abrupt ocean warming.

    Science.gov (United States)

    Praetorius, S K; Mix, A C; Walczak, M H; Wolhowe, M D; Addison, J A; Prahl, F G

    2015-11-19

    Marine sediments from the North Pacific document two episodes of expansion and strengthening of the subsurface oxygen minimum zone (OMZ) accompanied by seafloor hypoxia during the last deglacial transition. The mechanisms driving this hypoxia remain under debate. We present a new high-resolution alkenone palaeotemperature reconstruction from the Gulf of Alaska that reveals two abrupt warming events of 4-5 degrees Celsius at the onset of the Bølling and Holocene intervals that coincide with sudden shifts to hypoxia at intermediate depths. The presence of diatomaceous laminations and hypoxia-tolerant benthic foraminiferal species, peaks in redox-sensitive trace metals, and enhanced (15)N/(14)N ratio of organic matter, collectively suggest association with high export production. A decrease in (18)O/(16)O values of benthic foraminifera accompanying the most severe deoxygenation event indicates subsurface warming of up to about 2 degrees Celsius. We infer that abrupt warming triggered expansion of the North Pacific OMZ through reduced oxygen solubility and increased marine productivity via physiological effects; following initiation of hypoxia, remobilization of iron from hypoxic sediments could have provided a positive feedback on ocean deoxygenation through increased nutrient utilization and carbon export. Such a biogeochemical amplification process implies high sensitivity of OMZ expansion to warming.

  1. Hypoxic hypoxia at moderate altitudes: review of the state of the science.

    Science.gov (United States)

    Petrassi, Frank A; Hodkinson, Peter D; Walters, P Lynne; Gaydos, Steven J

    2012-10-01

    Unpressurized aircraft routinely operate at altitudes where hypoxia may be of concern. A systematic literature review was conducted regarding hypoxic impairment, including mental functions, sensory deficits, and other pertinent research findings that may affect aviation-related duties at moderate altitude (8000 to 15,000 ft/2438 to 4572 m). The results of this review suggest that cognitive and psychomotor deficits may include learning, reaction time, decision-making, and certain types of memory. However, results are difficult to quantify and reliably reproduce. Inconsistency of results may be related to the subtlety of deficits compared to high altitude, differences among individual compensatory mechanisms, variation in methodology or sensitivity of metrics, presence or absence of exercise, heterogeneous neuronal central nervous system (CNS) response, and interindividual variation. Literature regarding hypoxic visual decrements is more consistent. Rod photoreceptors are more susceptible to hypoxia; visual degradation has been demonstrated at 4000 to 5000 ft (1219 to 1524 m) under scotopic and 10,000 ft (3048 m) under photopic conditions. Augmented night vision goggle resolution demonstrates more resilience to mild hypoxic effects than the unaided eye under starlight conditions. Hypocapnia enhances visual sensitivity and contrast discrimination. Hyperventilation with resulting respiratory alkalosis and cerebral vasoconstriction may confound both cognitive/ psychomotor and visual experimental results. Future research should include augmentation of validated neuropsychological metrics (surrogate investigational end points) with actual flight metrics, investigation of mixed gas formulations, contribution of hypocapnic vasoconstrictive effects on hypoxic performance, and further investigation into cellular- and systems-level approaches for heterogeneous CNS response. Research is also required into the contribution of mild-moderate hypoxia in human factors- and spatial

  2. Sensitivity analysis and control of a cantilever beam by mean of a shunted piezoelectric patch

    OpenAIRE

    Matten, Gaël; Collet, Manuel; Sadoulet-Reboul, Emeline; Cogan, Scott

    2013-01-01

    International audience; In this paper, a sensitivity analysis of a beam controlled with a shunted piezoelectric patch is presented. A negative capacitance controller is implemented and a study of stability and performance is performed. Besides, the effects of the technological aspects such as the variability in the material properties or in the position of the piezoelectric patch is evaluated through a finite element simulation

  3. Design and Evaluation of Autonomous Hybrid Frequency-Voltage Sensitive Load Controller

    DEFF Research Database (Denmark)

    Douglass, Philip James; Garcia-Valle, Rodrigo; Sossan, Fabrizio;

    2013-01-01

    The paper introduces an algorithm for control of autonomous loads without digital communication interfaces to provide both frequency regulation and voltage regulation services. This hybrid controller can be used to enhance frequency sensitive loads to mitigate line overload arising from reduced...

  4. The Optimal Control for the Output Feedback Stochastic System at the Risk-Sensitive Cost

    Institute of Scientific and Technical Information of China (English)

    戴立言; 潘子刚; 施颂椒

    2003-01-01

    The optimal control of the partially observable stochastic system at the risk-sensitive cost is considered in this paper. The system dynamics has a general correlation between system and measurement noise. And the risk-sensitive cost contains a general quadratic term (with cross terms and extra linear terms). The explicit solution of such a problem is presented here using the output feedback control method. This clean and direct derivation enables one to convert such partial observable problems into the equivalent complete observable control problems and use the routine ways to solve them.

  5. POSTURAL CONTROL IN HEALTHY YOUNG ADULTS WITH AND WITHOUT CHRONIC MOTION SENSITIVITY

    Directory of Open Access Journals (Sweden)

    Alyahya D

    2016-02-01

    Full Text Available Background: Postural control requires complex processing of peripheral sensory inputs from the visual, somatosensory and vestibular systems. Motion sensitivity and decreased postural control are influenced by visual-vestibular conflicts.The purpose of this study was to measure the difference between the postural control of healthy adults with and without history of sub-clinical chronic motion sensitivity using a computerized dynamic posturography in a virtual reality environment. Sub-clinical chronic motion sensitivity was operationally defined as a history of avoiding activities causing dizziness, nausea, imbalance, and/or blurred vision without having a related medical diagnosis. Methods: Twenty healthy adults between 22 and 33 years of age participated in the study. Eleven subjects had sub-clinical chronic motion sensitivity and 9 subjects did not. Postural control was measured in both groups using the Bertec Balance Advantage-Dynamic Computerized Dynamic Posturography with Immersion Virtual Reality (CDP-IVR. The CDP-IVR reports an over-all equilibrium score based on subjects’ center of gravity displacement and postural sway while immersed in a virtual reality environment. Subjects were tested on stable (condition 1 and unstable (condition2 platform conditions. Results: There was no significant difference between the two groups in terms of mean age, height, weight, body mass index in kg/m2, postural control scores for conditions 2, and average (p>0.05. However, significant differences were observed in mean postural control for condition 1 between groups (p=0.03. Conclusions: Results of this study suggest that healthy young adults without chronic sub-clinical motion sensitivity have better postural control than those with chronic sub-clinical motion sensitivity. Further investigation is warranted to explore wider age ranges with larger samples sizes as well as intervention strategies to improve postural control.

  6. Hypoxic-ischemic changes in SIDS brains as demonstrated by a reduction in MAP2-reactive neurons.

    Science.gov (United States)

    Oehmichen, Manfred; Woetzel, Fabian; Meissner, Christoph

    2009-03-01

    Sudden infant death syndrome (SIDS) is characterized by a lack of any known morphological or functional organ changes that could explain the lethal process. In the present study we investigated the hypothesis of an association between hypoxic/ischemic injury and SIDS deaths. In a previous study, we could demonstrate by quantitative immunohistochemistry a distinct drop in microtubule-associated protein (MAP2) reactivity in neurons of adult, human brains secondary to acute hypoxic-ischemic injuries. Here we applied the same method on sections of the frontal cortex and hippocampus of 41 brains of infants younger than 1 year of age. For each brain area 100 selected neurons were evaluated for their MAP2 reactivity in the different layers of the frontal cortex and in the different segments of the hippocampus. Three groups were compared: (1) SIDS victims (n = 17), (2) infants with hypoxia/ischemia (control group one; n = 14), (3) infants without hypoxic/ischemic injury (control group two; n = 10). The SIDS group and hypoxic/ischemic group exhibited a general reduction in the number of MAP2 reactive neurons in comparison with the non-hypoxic/ischemic injury group. The SIDS group also had a significantly lower (P < 0.05) number of reactive neurons in the CA2 and CA3 areas of the hippocampus than did control group two. No difference was detected between the SIDS group and control group one. The SIDS brains were thus found to display hypoxic/ischemic features without however providing evidence as to the cause of the oxygen reduction.

  7. Application of a sensitivity analysis technique to high-order digital flight control systems

    Science.gov (United States)

    Paduano, James D.; Downing, David R.

    1987-01-01

    A sensitivity analysis technique for multiloop flight control systems is studied. This technique uses the scaled singular values of the return difference matrix as a measure of the relative stability of a control system. It then uses the gradients of these singular values with respect to system and controller parameters to judge sensitivity. The sensitivity analysis technique is first reviewed; then it is extended to include digital systems, through the derivation of singular-value gradient equations. Gradients with respect to parameters which do not appear explicitly as control-system matrix elements are also derived, so that high-order systems can be studied. A complete review of the integrated technique is given by way of a simple example: the inverted pendulum problem. The technique is then demonstrated on the X-29 control laws. Results show linear models of real systems can be analyzed by this sensitivity technique, if it is applied with care. A computer program called SVA was written to accomplish the singular-value sensitivity analysis techniques. Thus computational methods and considerations form an integral part of many of the discussions. A user's guide to the program is included. The SVA is a fully public domain program, running on the NASA/Dryden Elxsi computer.

  8. Toxic variability and radiation sensitization by Pt(II) analogs in Salmonella typhimurium cells

    Energy Technology Data Exchange (ETDEWEB)

    Richmond, R.C.; Khokhar, A.R.; Teicher, B.A.; Douple, E.B.

    1984-09-01

    A rationale is presented for the development of toxic, i.e., cytocidal, antitumor drugs as clinical hypoxic cell radiation sensitizers. Pt(II) complex-induced hypoxic cell radiation sensitization may occur from Pt(II) complex in free solution and Pt(II) bound to DNA. Although both the free solution and the bound compartments may operate, the free solution compartment is more likely amenable to experimental and clinical control in the case of systemically active Pt drugs. Assuming equivalent cell uptake of different Pt(II) complexes, the free solution compartment of Pt(II) sensitization can be increased by utilizing less toxic analogs of the antitumor drug cis-dichlorodiammineplatinum(II). One such less toxic Pt(II) sensitizer currently in clinical use is found to be cis-(1,1-cyclobutanedicarboxylato)diammineplatinum(II). A new finding of both clinical and mechanistic usefulness is described: irradiation of hypoxic solutions of four cis-Pt(II) complexes, but not two trans-Pt(II) complexes, creates products that cause toxicity in excees of the unirradiated solutions.

  9. Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Telang, F.; Baler, R.

    2010-07-01

    Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.

  10. Ghrelin Administration Increases the Bax/Bcl-2 Gene Expression Ratio in the Heart of Chronic Hypoxic Rats.

    Science.gov (United States)

    Aliparasti, Mohammad Reza; Alipour, Mohammad Reza; Almasi, Shohreh; Feizi, Hadi

    2015-06-01

    Programmed cell death or apoptosis, is a biochemical procedure that initiates due to some conditions, including hypoxia. Bax and Bcl-2 are among the agents that regulate apoptosis. The amplification of the first one triggers the initiation of apoptosis, and the second one prevents it. Ghrelin is an endogenous peptide that antiapoptosis is its new effect. The aim of this study is to examine the effect of ghrelin on the Bax/Bcl-2 ratio. Twenty four wistar rats were divided randomly in three groups; control, hypoxic + saline and hypoxic + ghrelin. Hypoxic animals lived in O2 11% for 2 weeks and received either saline or ghrelin subcutaneously daily. The bax and Bcl-2 gene expression were measured by Real-Time RT-PCR. Chronic hypoxia increased the Bax gene expression significantly compared with normal animals (P = 0.008), but the Bcl-2 was not affected by hypoxia. The Bax/Bcl-2 ratio also amplified significantly (P=0.005). Ghrelin administration significantly increased the Bax/Bcl-2 ratio in the hypoxic animals compared to the hypoxic + saline and normal groups (p=0.042 and P= 0.001, respectively). In the present study, animals' treatment with ghrelin leads to an increment of Bax/Bcl-2 ratio, which indicates a controversy related to cardioprotection of ghrelin.

  11. Ghrelin Administration Increases the Bax/Bcl-2 Gene Expression Ratio in the Heart of Chronic Hypoxic Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Aliparasti

    2015-06-01

    Full Text Available Purpose: Programmed cell death or apoptosis, is a biochemical procedure that initiates due to some conditions, including hypoxia. Bax and Bcl-2 are among the agents that regulate apoptosis. The amplification of the first one triggers the initiation of apoptosis, and the second one prevents it. Ghrelin is an endogenous peptide that antiapoptosis is its new effect. The aim of this study is to examine the effect of ghrelin on the Bax/Bcl-2 ratio. Methods: Twenty four wistar rats were divided randomly in three groups; control, hypoxic + saline and hypoxic + ghrelin. Hypoxic animals lived in O2 11% for 2 weeks and received either saline or ghrelin subcutaneously daily. The bax and Bcl-2 gene expression were measured by Real-Time RT-PCR. Results: Chronic hypoxia increased the Bax gene expression significantly compared with normal animals (P = 0.008, but the Bcl-2 was not affected by hypoxia. The Bax/Bcl-2 ratio also amplified significantly (P=0.005. Ghrelin administration significantly increased the Bax/Bcl-2 ratio in the hypoxic animals compared to the hypoxic + saline and normal groups (p=0.042 and P= 0.001, respectively. Conclusion: In the present study, animals’ treatment with ghrelin leads to an increment of Bax/Bcl-2 ratio, which indicates a controversy related to cardioprotection of ghrelin.

  12. Ghrelin Administration Increases the Bax/Bcl-2 Gene Expression Ratio in the Heart of Chronic Hypoxic Rats

    Science.gov (United States)

    Aliparasti, Mohammad Reza; Alipour, Mohammad Reza; Almasi, Shohreh; Feizi, Hadi

    2015-01-01

    Purpose: Programmed cell death or apoptosis, is a biochemical procedure that initiates due to some conditions, including hypoxia. Bax and Bcl-2 are among the agents that regulate apoptosis. The amplification of the first one triggers the initiation of apoptosis, and the second one prevents it. Ghrelin is an endogenous peptide that antiapoptosis is its new effect. The aim of this study is to examine the effect of ghrelin on the Bax/Bcl-2 ratio. Methods: Twenty four wistar rats were divided randomly in three groups; control, hypoxic + saline and hypoxic + ghrelin. Hypoxic animals lived in O2 11% for 2 weeks and received either saline or ghrelin subcutaneously daily. The bax and Bcl-2 gene expression were measured by Real-Time RT-PCR. Results: Chronic hypoxia increased the Bax gene expression significantly compared with normal animals (P = 0.008), but the Bcl-2 was not affected by hypoxia. The Bax/Bcl-2 ratio also amplified significantly (P=0.005). Ghrelin administration significantly increased the Bax/Bcl-2 ratio in the hypoxic animals compared to the hypoxic + saline and normal groups (p=0.042 and P= 0.001, respectively). Conclusion: In the present study, animals’ treatment with ghrelin leads to an increment of Bax/Bcl-2 ratio, which indicates a controversy related to cardioprotection of ghrelin. PMID:26236657

  13. Heart rate response to hypoxic exercise

    DEFF Research Database (Denmark)

    Lundby, C; Møller, P; Kanstrup, I L

    2001-01-01

    This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed...... two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia...... breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels...

  14. Targeting hypoxic response for cancer therapy

    Science.gov (United States)

    Paolicchi, Elisa; Gemignani, Federica; Krstic-Demonacos, Marija; Dedhar, Shoukat; Mutti, Luciano; Landi, Stefano

    2016-01-01

    Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as “Warburg effect” and the “reverse Warburg effect”. This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells. PMID:26859576

  15. Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications.

    Science.gov (United States)

    Lumb, Andrew B; Slinger, Peter

    2015-04-01

    Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference between the pulmonary and systemic circulations. HPV is active in utero, reducing pulmonary blood flow, and in adults helps to match regional ventilation and perfusion although it has little effect in healthy lungs. Many factors affect HPV including pH or PCO2, cardiac output, and several drugs, including antihypertensives. In patients with lung pathology and any patient having one-lung ventilation, HPV contributes to maintaining oxygenation, so anesthesiologists should be aware of the effects of anesthesia on this protective reflex. Intravenous anesthetic drugs have little effect on HPV, but it is attenuated by inhaled anesthetics, although less so with newer agents. The reflex is biphasic, and once the second phase becomes active after about an hour of hypoxia, this pulmonary vasoconstriction takes hours to reverse when normoxia returns. This has significant clinical implications for repeated periods of one-lung ventilation.

  16. Computational Study of pH-sensitive Hydrogel-based Microfluidic Flow Controllers

    Directory of Open Access Journals (Sweden)

    Jundika C. Kurnia

    2011-08-01

    Full Text Available This computational study investigates the sensing and actuating behavior of a pH-sensitive hydrogel-based microfluidic flow controller. This hydrogel-based flow controller has inherent advantage in its unique stimuli-sensitive properties, removing the need for an external power supply. The predicted swelling behavior the hydrogel is validated with steady-state and transient experiments. We then demonstrate how the model is implemented to study the sensing and actuating behavior of hydrogels for different microfluidic flow channel/hydrogel configurations: e.g., for flow in a T-junction with single and multiple hydrogels. In short, the results suggest that the response of the hydrogel-based flow controller is slow. Therefore, two strategies to improve the response rate of the hydrogels are proposed and demonstrated. Finally, we highlight that the model can be extended to include other stimuli-responsive hydrogels such as thermo-, electric-, and glucose-sensitive hydrogels.

  17. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury

    OpenAIRE

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-01-01

    Abstract The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI). Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correla...

  18. Slow breathing and hypoxic challenge: cardiorespiratory consequences and their central neural substrates.

    Science.gov (United States)

    Critchley, Hugo D; Nicotra, Alessia; Chiesa, Patrizia A; Nagai, Yoko; Gray, Marcus A; Minati, Ludovico; Bernardi, Luciano

    2015-01-01

    Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.

  19. A Framework for Context Sensitive Risk-Based Access Control in Medical Information Systems.

    Science.gov (United States)

    Choi, Donghee; Kim, Dohoon; Park, Seog

    2015-01-01

    Since the access control environment has changed and the threat of insider information leakage has come to the fore, studies on risk-based access control models that decide access permissions dynamically have been conducted vigorously. Medical information systems should protect sensitive data such as medical information from insider threat and enable dynamic access control depending on the context such as life-threatening emergencies. In this paper, we suggest an approach and framework for context sensitive risk-based access control suitable for medical information systems. This approach categorizes context information, estimating and applying risk through context- and treatment-based permission profiling and specifications by expanding the eXtensible Access Control Markup Language (XACML) to apply risk. The proposed framework supports quick responses to medical situations and prevents unnecessary insider data access through dynamic access authorization decisions in accordance with the severity of the context and treatment.

  20. Effect of breviscapine on fractalkine expression in chronic hypoxic rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-ju; CHENG De-yun; YANG Li; XIA Xiu-qiong; GUAN Jian

    2006-01-01

    @@ Fractalkine (FKN) is the only known chemokine that fulfils the dual functions of an adhesive molecule and a soluble chemoattractant.1 FKN expression was reported increase in lungs of patients with severe pulmonary arterial hypertension,2 suggesting that FKN may participate in pathogenesis of pulmonary hypertension.Breviscapine is a flavonoid extracted from Erigeron breviscapus (Vant.) Hand. Mazz. Breviscapine can prevent the development of hypoxic pulmonary hypertension3 but the mechanism is unknown. This study evaluated the role of FKN in the pathogenesis of hypoxic pulmonary hypertension and the effect of breviscapine on FKN in hypoxic pulmonary hypertension.

  1. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

    Science.gov (United States)

    Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

    2013-01-01

    Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

  2. Post-hypoxic recovery of respiratory rhythm generation is gender dependent.

    Directory of Open Access Journals (Sweden)

    Alfredo J Garcia

    Full Text Available The preBötzinger complex (preBötC is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. Recordings of respiratory activity from neonatal mice (P10-13 show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBötC in neonatal brainstem slices (P10-13 reveal that the time to the first inspiratory burst following reoxygenation (TTFB is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (KATP with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBötC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS.

  3. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of 123I-IAZA

    Directory of Open Access Journals (Sweden)

    Leonard I. Wiebe

    2002-09-01

    Full Text Available Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. The presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes,or as a prognostic indicator for management of the disease (e.g. stroke. Over the past two decades, a number of hypoxia radioimaging agents have been developed and tested clinically. Of these, 18F-Fmiso and 123I-IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fmiso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumour to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetics. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. 18F-Fmiso and 123I-IAZA have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with 123I-IAZA , an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical applications.Os tecidos

  4. Analysis of heart rate control to assess thermal sensitivity responses in Brazilian toads

    Directory of Open Access Journals (Sweden)

    J.E.S. Natali

    2015-01-01

    Full Text Available In anurans, changes in ambient temperature influence body temperature and, therefore, energy consumption. These changes ultimately affect energy supply and, consequently, heart rate (HR. Typically, anurans living in different thermal environments have different thermal sensitivities, and these cannot be distinguished by changes in HR. We hypothesized that Rhinella jimi (a toad from a xeric environment that lives in a wide range of temperatures would have a lower thermal sensitivity regarding cardiac control than R. icterica (originally from a tropical forest environment with a more restricted range of ambient temperatures. Thermal sensitivity was assessed by comparing animals housed at 15° and 25°C. Cardiac control was estimated by heart rate variability (HRV and heart rate complexity (HRC. Differences in HRV between the two temperatures were not significant (P=0.214 for R. icterica and P=0.328 for R. jimi, whereas HRC differences were. All specimens but one R. jimi had a lower HRC at 15°C (all P<0.01. These results indicate that R. jimi has a lower thermal sensitivity and that cardiac control is not completely dependent on the thermal environment because HRC was not consistently different between temperatures in all R. jimi specimens. This result indicates a lack of evolutive trade-offs among temperatures given that heart rate control at 25°C is potentially not a constraint to heart rate control at 15°C.

  5. Analysis of heart rate control to assess thermal sensitivity responses in Brazilian toads.

    Science.gov (United States)

    Natali, J E S; Santos, B T; Rodrigues, V H; Chauí-Berlinck, J G

    2015-01-01

    In anurans, changes in ambient temperature influence body temperature and, therefore, energy consumption. These changes ultimately affect energy supply and, consequently, heart rate (HR). Typically, anurans living in different thermal environments have different thermal sensitivities, and these cannot be distinguished by changes in HR. We hypothesized that Rhinella jimi (a toad from a xeric environment that lives in a wide range of temperatures) would have a lower thermal sensitivity regarding cardiac control than R. icterica (originally from a tropical forest environment with a more restricted range of ambient temperatures). Thermal sensitivity was assessed by comparing animals housed at 15° and 25°C. Cardiac control was estimated by heart rate variability (HRV) and heart rate complexity (HRC). Differences in HRV between the two temperatures were not significant (P=0.214 for R. icterica and P=0.328 for R. jimi), whereas HRC differences were. All specimens but one R. jimi had a lower HRC at 15°C (all P<0.01). These results indicate that R. jimi has a lower thermal sensitivity and that cardiac control is not completely dependent on the thermal environment because HRC was not consistently different between temperatures in all R. jimi specimens. This result indicates a lack of evolutive trade-offs among temperatures given that heart rate control at 25°C is potentially not a constraint to heart rate control at 15°C.

  6. A Stochastic Maximum Principle for Risk-Sensitive Mean-Field Type Control

    KAUST Repository

    Djehiche, Boualem

    2015-02-24

    In this paper we study mean-field type control problems with risk-sensitive performance functionals. We establish a stochastic maximum principle (SMP) for optimal control of stochastic differential equations (SDEs) of mean-field type, in which the drift and the diffusion coefficients as well as the performance functional depend not only on the state and the control but also on the mean of the distribution of the state. Our result extends the risk-sensitive SMP (without mean-field coupling) of Lim and Zhou (2005), derived for feedback (or Markov) type optimal controls, to optimal control problems for non-Markovian dynamics which may be time-inconsistent in the sense that the Bellman optimality principle does not hold. In our approach to the risk-sensitive SMP, the smoothness assumption on the value-function imposed in Lim and Zhou (2005) needs not be satisfied. For a general action space a Peng\\'s type SMP is derived, specifying the necessary conditions for optimality. Two examples are carried out to illustrate the proposed risk-sensitive mean-field type SMP under linear stochastic dynamics with exponential quadratic cost function. Explicit solutions are given for both mean-field free and mean-field models.

  7. Dynamic hypoxic zones in Lake Erie compress fish habitat, altering vulnerability to fishing gears

    Science.gov (United States)

    Kraus, Richard T.; Knight, Carey T.; Farmer, Troy M.; Gorman, Ann Marie; Collingsworth, Paris D.; Warren, Glenn J.; Kocovsky, Patrick M.; Conroy, Joseph D.

    2015-01-01

    Seasonal degradation of aquatic habitats from hypoxia occurs in numerous freshwater and coastal marine systems and can result in direct mortality or displacement of fish. Yet, fishery landings from these systems are frequently unresponsive to changes in the severity and extent of hypoxia, and population-scale effects have been difficult to measure except in extreme hypoxic conditions with hypoxia-sensitive species. We investigated fine-scale temporal and spatial variability in dissolved oxygen in Lake Erie as it related to fish distribution and catch efficiencies of both active (bottom trawls) and passive (trap nets) fishing gears. Temperature and dissolved oxygen loggers placed near the edge of the hypolimnion exhibited much higher than expected variability. Hypoxic episodes of variable durations were frequently punctuated by periods of normoxia, consistent with high-frequency internal waves. High-resolution interpolations of water quality and hydroacoustic surveys suggest that fish habitat is compressed during hypoxic episodes, resulting in higher fish densities near the edges of hypoxia. At fixed locations with passive commercial fishing gear, catches with the highest values occurred when bottom waters were hypoxic for intermediate proportions of time. Proximity to hypoxia explained significant variation in bottom trawl catches, with higher catch rates near the edge of hypoxia. These results emphasize how hypoxia may elevate catch rates in various types of fishing gears, leading to a lack of association between indices of hypoxia and fishery landings. Increased catch rates of fish at the edges of hypoxia have important implications for stock assessment models that assume catchability is spatially homogeneous.

  8. Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Sean Carlin

    Full Text Available BACKGROUND: Carbonic anhydrase IX (CAIX is a membrane spanning protein involved in the enzymatic regulation of tumor acid-base balance. CAIX has been shown to be elevated in a number of hypoxic tumor types. The purpose of this study was to determine the efficiency of intact and IgG fragments of cG250 to target CAIX in vivo in a hypoxic tumor model. METHODOLOGY/PRINCIPAL FINDINGS: Conventional biodistribution studies were performed with (111In-DO3A-cG250, (111In-DO3A-F(ab'(2-cG250 and (111In-DO3A-Fab-cG250. Additional ex vivo analysis of the tumor was performed with markers for tumor hypoxia, blood perfusion and endogenous CAIX expression. All four data sets were digitally correlated to determine the optimal agent for determining hypoxia in a HT29 colon cancer xenograft. The HT29 human colorectal tumor xenografts show strong CAIX expression in hypoxic areas of poor blood perfusion. The intact IgG had an initial high focal uptake at the periphery of these hypoxic regions and penetration into the areas of highest CAIX expression over the 7-day study period. The lower molecular weight antibody fragments had a faster uptake into areas of high CAIX expression, but had a much lower absolute uptake at the optimal imaging times. CONCLUSIONS/SIGNIFICANCE: For the clinical detection of hypoxia induced CAIX using cG250 antibody based agents, imaging with the intact IgG at 7 days post injection would allow for the most sensitive and accurate detection of CAIX.

  9. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Directory of Open Access Journals (Sweden)

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  10. Control of in vivo (cellular) phleomycin sensitivity by nuclear genotype, growth phase, and metal ions

    Energy Technology Data Exchange (ETDEWEB)

    Moore, C.W.

    1982-03-01

    Nuclear genotype, growth phase, and the presence of metal ions all proved to be important in controlling the lethal effects of phleomycin in eukaryotic Saccharomyces cerevisiae. Among 120 normal and radiation-sensitive strains compared for their sensitivities to lethal effects of phleomycin, all mutant strains exhibiting enhanced sensitivities to phleomycin killing were also sensitive to killing by ionizing radiation. Mutants exhibiting sensitivities to phleomycin similar to normal strains of the same ploidy were sensitive to ultraviolet radiation. We conclude that cellular recovery from phleomycin-induced damage in yeast depends upon the function of some or all of 13 independent genes and upon at least some of the same steps in cellular pathways for the biological repair of damage by ionizing radiation. In this respect, the action of phleomycin is similar to the action of its structurally similar analog, bleomycin, even though phleomycin was substantially more cytotoxic. Stationary-phase haploid yeast cells were more sensitive than exponentially growing cells to killing by phleomycin. Survival of stationary-phase yeast was reduced to 0.3 +/- 0.07% (S.E.) after 20-min exposures to phleomycin (1 microgram/ml; approximately 6.7 x 10(-7) M), but lethal effects of phleomycin were completely eradicated (98% survival) by the presence of 0.05 M ethylenediaminetetraacetate during the treatment period. The inactivation indicates an important role for one or more metal ion(s) in the in vivo toxicity of the phleomycin-bleomycin group of anticancer antibiotics.

  11. [Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Nuñez, Antonio; Benavente, Isabel; Blanco, Dorotea; Boix, Héctor; Cabañas, Fernando; Chaffanel, Mercedes; Fernández-Colomer, Belén; Fernández-Lorenzo, José Ramón; Loureiro, Begoña; Moral, María Teresa; Pavón, Antonio; Tofé, Inés; Valverde, Eva; Vento, Máximo

    2017-06-22

    Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  12. An approach of optimal sensitivity applied in the tertiary loop of the automatic generation control

    Energy Technology Data Exchange (ETDEWEB)

    Belati, Edmarcio A. [CIMATEC - SENAI, Salvador, BA (Brazil); Alves, Dilson A. [Electrical Engineering Department, FEIS, UNESP - Sao Paulo State University (Brazil); da Costa, Geraldo R.M. [Electrical Engineering Department, EESC, USP - Sao Paulo University (Brazil)

    2008-09-15

    This paper proposes an approach of optimal sensitivity applied in the tertiary loop of the automatic generation control. The approach is based on the theorem of non-linear perturbation. From an optimal operation point obtained by an optimal power flow a new optimal operation point is directly determined after a perturbation, i.e., without the necessity of an iterative process. This new optimal operation point satisfies the constraints of the problem for small perturbation in the loads. The participation factors and the voltage set point of the automatic voltage regulators (AVR) of the generators are determined by the technique of optimal sensitivity, considering the effects of the active power losses minimization and the network constraints. The participation factors and voltage set point of the generators are supplied directly to a computational program of dynamic simulation of the automatic generation control, named by power sensitivity mode. Test results are presented to show the good performance of this approach. (author)

  13. Optimal control and sensitivity analysis of an influenza model with treatment and vaccination.

    Science.gov (United States)

    Tchuenche, J M; Khamis, S A; Agusto, F B; Mpeshe, S C

    2011-03-01

    We formulate and analyze the dynamics of an influenza pandemic model with vaccination and treatment using two preventive scenarios: increase and decrease in vaccine uptake. Due to the seasonality of the influenza pandemic, the dynamics is studied in a finite time interval. We focus primarily on controlling the disease with a possible minimal cost and side effects using control theory which is therefore applied via the Pontryagin's maximum principle, and it is observed that full treatment effort should be given while increasing vaccination at the onset of the outbreak. Next, sensitivity analysis and simulations (using the fourth order Runge-Kutta scheme) are carried out in order to determine the relative importance of different factors responsible for disease transmission and prevalence. The most sensitive parameter of the various reproductive numbers apart from the death rate is the inflow rate, while the proportion of new recruits and the vaccine efficacy are the most sensitive parameters for the endemic equilibrium point.

  14. Enhancement and control of surface plasmon resonance sensitivity using grating in conical mounting configuration.

    Science.gov (United States)

    Perino, M; Pasqualotto, E; Scaramuzza, M; De Toni, A; Paccagnella, A

    2015-01-15

    In this work we propose a method to enhance and control the angular sensitivity of a grating coupled surface plasmon resonance (GCSPR) sensor. We lighted a silver grating, mounted in conical configuration, with a laser source and we measured the transmittance of the grating as a function of the azimuthal angle. To evaluate the sensitivity, grating surface was functionalized with four different alkanethiol self assembled monolayers (SAM) and the correspondent azimuthal transmittance peak shifts were measured. The sensitivity control was performed by simply change the light incident angle. This method offers the possibility to design dynamic GCSPR sensor benches that can be used to amplify the SPR angle shift at any step of a biological detection process.

  15. The Hypoxic Regulator of Sterol Synthesis Nro1 Is a Nuclear Import Adaptor

    Energy Technology Data Exchange (ETDEWEB)

    T Yeh; C Lee; L Amzel; P Espenshade; M Bianchet

    2011-12-31

    Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 {angstrom} resolution shows an all-{alpha}-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both in Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.

  16. Uncertainty and sensitivity analysis of control strategies using the benchmark simulation model No1 (BSM1)

    DEFF Research Database (Denmark)

    Flores-Alsina, Xavier; Rodriguez-Roda, Ignasi; Sin, Gürkan

    2009-01-01

    The objective of this paper is to perform an uncertainty and sensitivity analysis of the predictions of the Benchmark Simulation Model (BSM) No. 1, when comparing four activated sludge control strategies. The Monte Carlo simulation technique is used to evaluate the uncertainty in the BSM1 predict...

  17. Distinct neuropsychological profiles within ADHD : A latent class analysis of cognitive control, reward sensitivity and timing

    NARCIS (Netherlands)

    Van Hulst, B. M.; De Zeeuw, P.; Durston, S.

    2015-01-01

    Background. Multiple pathway models of attention deficit hyperactivity disorder (ADHD) suggest that this disorder is the behavioural expression of dysfunction in one of several separable brain systems. One such model focuses on the brain systems underlying cognitive control, timing and reward sensit

  18. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity

    OpenAIRE

    Clemmons, David R.

    2004-01-01

    IGF-1 and growth hormone (GH) interact with insulin to modulate its control of carbohydrate metabolism. A new study (see the related article beginning on page 96) shows that blocking the effect of GH in the presence of low serum IGF-1 concentrations enhances insulin sensitivity.

  19. Detection of vulnerable relays and sensitive controllers under cascading events based on performance indices

    DEFF Research Database (Denmark)

    Liu, Zhou; Chen, Zhe; Hu, Yanting

    2014-01-01

    The unexpected relay operations have been regarded as one of main reasons to propagate and induce the cascaded blackouts. It is significant to timely detect vulnerable relays to be blocked, and locate sensitive controllers to regulate the emergency states. In this paper, a multi agent system (MAS...

  20. A case of hypoxic encephalopathy with delayed exacerbation

    Directory of Open Access Journals (Sweden)

    Takeshi Hayashi

    2008-10-01

    Full Text Available Takeshi Hayashi, Kimihiko HattoriDepartment of Neurology, Fuji Heavy Industries Health Insurance Corporation, Ota General Hospital, Ota, Gunma, JapanAbstract: Most patients contract hypoxic encephalopathy after suffering a cardiac arrest. They usually endure severe neurological sequelae and the temporal profile of the disease progression remains unclear. This case study shows how the effects of hypoxic encephalopathy continue to progress for several years after the initial event. Up to eight years after the hypoxic insult, the patient’s intellect steadily deteriorated, and brain atrophy progressed. As the hypoxic insult on the brain is only transient, the neurological disability seems not to be exacerbated for years. However, our case indicates that this disorder may have a long progression.Keywords: dementia, encephalopathy, hypoxia, MRI

  1. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Espinoza, I., E-mail: iespinoza@fis.puc.cl [Institute of Physics, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany); Peschke, P. [Clinical Cooperation Unit Molecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany); Karger, C. P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany)

    2015-01-15

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  2. A case of hypoxic encephalopathy with delayed exacerbation

    OpenAIRE

    2008-01-01

    Takeshi Hayashi, Kimihiko HattoriDepartment of Neurology, Fuji Heavy Industries Health Insurance Corporation, Ota General Hospital, Ota, Gunma, JapanAbstract: Most patients contract hypoxic encephalopathy after suffering a cardiac arrest. They usually endure severe neurological sequelae and the temporal profile of the disease progression remains unclear. This case study shows how the effects of hypoxic encephalopathy continue to progress for several years after the initial event. Up to eight ...

  3. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF,vascular endothelial growth factor A (VEGF-A interleukin 6 (IL-6 and interleukin 8 (IL-8 under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM vs. normoxic BM-MSC-derived conditioned medium (norCM or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.

  4. NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive cerebrovasodilation impairment.

    Science.gov (United States)

    Armstead, William M

    2002-05-01

    Previous studies have observed that hypotensive pial artery dilation was blunted after hypoxia-ischemia. In unrelated studies, the opioid nociceptin/orphanin FQ (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D-aspartate (NMDA)-induced pial dilation. This study determined the contribution of NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment in newborn pigs equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased PO(2) to 33 +/- 3 mm Hg. Topical NOC/oFQ (10(-10) M), the cerebrospinal fluid concentration after hypoxia-ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) -induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial artery dilation was blunted by hypoxia-ischemia, but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M; 29 +/- 2%, sham control; 7 +/- 2%, hypoxia-ischemia; and 13 +/- 2%, hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH(2)). Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10(-10) M) partially prevented hypotensive pial dilation impairment. Similarly, pretreatment with MK801 partially protected hypoxic ischemia impairment of hypotensive pial dilation (35 +/- 2%, sham control; 7 +/- 1%, hypoxia-ischemia; 22 +/- 2%, hypoxia-ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic ischemic hypotensive cerebrovasodilation impairment. These data suggest that NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive impairment.

  5. Video-feedback intervention increases sensitive parenting in ethnic minority mothers: a randomized control trial.

    Science.gov (United States)

    Yagmur, Sengul; Mesman, Judi; Malda, Maike; Bakermans-Kranenburg, Marian J; Ekmekci, Hatice

    2014-01-01

    Using a randomized control trial design we tested the effectiveness of a culturally sensitive adaptation of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) in a sample of 76 Turkish minority families in the Netherlands. The VIPP-SD was adapted based on a pilot with feedback of the target mothers, resulting in the VIPP-TM (VIPP-Turkish Minorities). The sample included families with 20-47-month-old children with high levels of externalizing problems. Maternal sensitivity, nonintrusiveness, and discipline strategies were observed during pretest and posttest home visits. The VIPP-TM was effective in increasing maternal sensitivity and nonintrusiveness, but not in enhancing discipline strategies. Applying newly learned sensitivity skills in discipline situations may take more time, especially in a cultural context that favors more authoritarian strategies. We conclude that the VIPP-SD program and its video-feedback approach can be successfully applied in immigrant families with a non-Western cultural background, with demonstrated effects on parenting sensitivity and nonintrusiveness.

  6. Sensitivity Analysis of Linear Programming and Quadratic Programming Algorithms for Control Allocation

    Science.gov (United States)

    Frost, Susan A.; Bodson, Marc; Acosta, Diana M.

    2009-01-01

    The Next Generation (NextGen) transport aircraft configurations being investigated as part of the NASA Aeronautics Subsonic Fixed Wing Project have more control surfaces, or control effectors, than existing transport aircraft configurations. Conventional flight control is achieved through two symmetric elevators, two antisymmetric ailerons, and a rudder. The five effectors, reduced to three command variables, produce moments along the three main axes of the aircraft and enable the pilot to control the attitude and flight path of the aircraft. The NextGen aircraft will have additional redundant control effectors to control the three moments, creating a situation where the aircraft is over-actuated and where a simple relationship does not exist anymore between the required effector deflections and the desired moments. NextGen flight controllers will incorporate control allocation algorithms to determine the optimal effector commands and attain the desired moments, taking into account the effector limits. Approaches to solving the problem using linear programming and quadratic programming algorithms have been proposed and tested. It is of great interest to understand their relative advantages and disadvantages and how design parameters may affect their properties. In this paper, we investigate the sensitivity of the effector commands with respect to the desired moments and show on some examples that the solutions provided using the l2 norm of quadratic programming are less sensitive than those using the l1 norm of linear programming.

  7. Deficits in cognitive control, timing and reward sensitivity appear to be dissociable in ADHD.

    Science.gov (United States)

    de Zeeuw, Patrick; Weusten, Juliette; van Dijk, Sarai; van Belle, Janna; Durston, Sarah

    2012-01-01

    Recent neurobiological models of ADHD suggest that deficits in different neurobiological pathways may independently lead to symptoms of this disorder. At least three independent pathways may be involved: a dorsal frontostriatal pathway involved in cognitive control, a ventral frontostriatal pathway involved in reward processing and a frontocerebellar pathway related to temporal processing. Importantly, we and others have suggested that disruptions in these three pathways should lead to separable deficits at the cognitive level. Furthermore, if these truly represent separate biological pathways to ADHD, these cognitive deficits should segregate between individuals with ADHD. The present study tests these hypotheses in a sample of children, adolescents and young adults with ADHD and controls. 149 Subjects participated in a short computerized battery assessing cognitive control, timing and reward sensitivity. We used Principal Component Analysis to find independent components underlying the variance in the data. The segregation of deficits between individuals was tested using Loglinear Analysis. We found four components, three of which were predicted by the model: Cognitive control, reward sensitivity and timing. Furthermore, 80% of subjects with ADHD that had a deficit were deficient on only one component. Loglinear Analysis statistically confirmed the independent segregation of deficits between individuals. We therefore conclude that cognitive control, timing and reward sensitivity were separable at a cognitive level and that deficits on these components segregated between individuals with ADHD. These results support a neurobiological framework of separate biological pathways to ADHD with separable cognitive deficits.

  8. Deficits in cognitive control, timing and reward sensitivity appear to be dissociable in ADHD.

    Directory of Open Access Journals (Sweden)

    Patrick de Zeeuw

    Full Text Available Recent neurobiological models of ADHD suggest that deficits in different neurobiological pathways may independently lead to symptoms of this disorder. At least three independent pathways may be involved: a dorsal frontostriatal pathway involved in cognitive control, a ventral frontostriatal pathway involved in reward processing and a frontocerebellar pathway related to temporal processing. Importantly, we and others have suggested that disruptions in these three pathways should lead to separable deficits at the cognitive level. Furthermore, if these truly represent separate biological pathways to ADHD, these cognitive deficits should segregate between individuals with ADHD. The present study tests these hypotheses in a sample of children, adolescents and young adults with ADHD and controls. 149 Subjects participated in a short computerized battery assessing cognitive control, timing and reward sensitivity. We used Principal Component Analysis to find independent components underlying the variance in the data. The segregation of deficits between individuals was tested using Loglinear Analysis. We found four components, three of which were predicted by the model: Cognitive control, reward sensitivity and timing. Furthermore, 80% of subjects with ADHD that had a deficit were deficient on only one component. Loglinear Analysis statistically confirmed the independent segregation of deficits between individuals. We therefore conclude that cognitive control, timing and reward sensitivity were separable at a cognitive level and that deficits on these components segregated between individuals with ADHD. These results support a neurobiological framework of separate biological pathways to ADHD with separable cognitive deficits.

  9. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

    Science.gov (United States)

    Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

    2017-01-01

    Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

  10. Sensitivity analysis of automatic flight control systems using singular value concepts

    Science.gov (United States)

    Herrera-Vaillard, A.; Paduano, J.; Downing, D.

    1985-01-01

    A sensitivity analysis is presented that can be used to judge the impact of vehicle dynamic model variations on the relative stability of multivariable continuous closed-loop control systems. The sensitivity analysis uses and extends the singular-value concept by developing expressions for the gradients of the singular value with respect to variations in the vehicle dynamic model and the controller design. Combined with a priori estimates of the accuracy of the model, the gradients are used to identify the elements in the vehicle dynamic model and controller that could severely impact the system's relative stability. The technique is demonstrated for a yaw/roll damper stability augmentation designed for a business jet.

  11. Sensitivity analysis of automatic flight control systems using singular value concepts

    Science.gov (United States)

    Herrera-Vaillard, A.; Paduano, J.; Downing, D.

    1985-01-01

    A sensitivity analysis is presented that can be used to judge the impact of vehicle dynamic model variations on the relative stability of multivariable continuous closed-loop control systems. The sensitivity analysis uses and extends the singular-value concept by developing expressions for the gradients of the singular value with respect to variations in the vehicle dynamic model and the controller design. Combined with a priori estimates of the accuracy of the model, the gradients are used to identify the elements in the vehicle dynamic model and controller that could severely impact the system's relative stability. The technique is demonstrated for a yaw/roll damper stability augmentation designed for a business jet.

  12. Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

    Science.gov (United States)

    Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

    2003-01-01

    Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

  13. A case-control study of wood dust exposure, mutagen sensitivity, and lung cancer risk.

    Science.gov (United States)

    Wu, X; Delclos, G L; Annegers, J F; Bondy, M L; Honn, S E; Henry, B; Hsu, T C; Spitz, M R

    1995-09-01

    The associations between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust, were assessed in a hospital-based case-control study. There were 113 African -American and 67 Mexican-American cases with newly diagnosed, previously untreated lung cancer and 270 controls, frequency-matched on age, ethnicity, and sex. Mutagen sensitivity ( 1 chromatid break/cell after short-term bleomycin treatment) was associated with statistically significant elevated risk for lung cancer [odds ration (OR) = 4.3; 95% confidence intervals (CI) = 2.3-7.9]. Wood dust exposure was also a significant predictor of risk (overall OR = 3.5; CI = 1.4-8.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was s significant risk factor for African-Americans (OR = 5.5; CI = 1.6-18.9) but not for Mexican-Americans (OR = 2.0; CI = 0.5-8.1). The ORs were 3.8 and 4.8 for non-small cell lung cancer in Mexican-Americans (CI = 1.2-18.5). Stratified analysis suggested evidence of strong interactions between wood dust exposure and both mutagen sensitivity and smoking in lung cancer risk.

  14. Executive control over unconscious cognition: attentional sensitization of unconscious information processing.

    Science.gov (United States)

    Kiefer, Markus

    2012-01-01

    Unconscious priming is a prototypical example of an automatic process, which is initiated without deliberate intention. Classical theories of automaticity assume that such unconscious automatic processes occur in a purely bottom-up driven fashion independent of executive control mechanisms. In contrast to these classical theories, our attentional sensitization model of unconscious information processing proposes that unconscious processing is susceptible to executive control and is only elicited if the cognitive system is configured accordingly. It is assumed that unconscious processing depends on attentional amplification of task-congruent processing pathways as a function of task sets. This article provides an overview of the latest research on executive control influences on unconscious information processing. I introduce refined theories of automaticity with a particular focus on the attentional sensitization model of unconscious cognition which is specifically developed to account for various attentional influences on different types of unconscious information processing. In support of the attentional sensitization model, empirical evidence is reviewed demonstrating executive control influences on unconscious cognition in the domains of visuo-motor and semantic processing: subliminal priming depends on attentional resources, is susceptible to stimulus expectations and is influenced by action intentions and task sets. This suggests that even unconscious processing is flexible and context-dependent as a function of higher-level executive control settings. I discuss that the assumption of attentional sensitization of unconscious information processing can accommodate conflicting findings regarding the automaticity of processes in many areas of cognition and emotion. This theoretical view has the potential to stimulate future research on executive control of unconscious processing in healthy and clinical populations.

  15. Hypoxic Hepatitis: A Review and Clinical Update

    Science.gov (United States)

    Waseem, Najeff; Chen, Po-Hung

    2016-01-01

    Abstract Hypoxic hepatitis (HH), also known as ischemic hepatitis or shock liver, is characterized by a massive, rapid rise in serum aminotransferases resulting from reduced oxygen delivery to the liver. The most common predisposing condition is cardiac failure, followed by circulatory failure as occurs in septic shock and respiratory failure. HH does, however, occur in the absence of a documented hypotensive event or shock state in 50% of patients. In intensive care units, the incidence of HH is near 2.5%, but has been reported as high as 10% in some studies. The pathophysiology is multifactorial, but often involves hepatic congestion from right heart failure along with reduced hepatic blood flow, total body hypoxemia, reduced oxygen uptake by hepatocytes or reperfusion injury following ischemia. The diagnosis is primarily clinical, and typically does not require liver biopsy. The definitive treatment of HH involves correction of the underlying disease state, but successful management includes monitoring for the potential complications such as hypoglycemia, hyperglycemia, hyperammonemia and hepatopulmonary syndrome. Prognosis of HH remains poor, especially for cases in which there was a delay in diagnosis. The in-hospital mortality rate is >50%, and the most frequent cause of death is the predisposing condition and not the liver injury itself. PMID:27777895

  16. Mass Law Predicts Hyperbolic Hypoxic Ventilatory Response

    Science.gov (United States)

    Severinghaus, John W.

    The hyperbolic hypoxic ventilatory response vs PaO2, HVRp, is interpreted as relecting a mass hyperbolic relationship of cytochrome PcO2 to cytochrome potential Ec, offset 32 torr by the constant diffusion gradient between arterial blood and cytochrome in CB at its constant metabolic rate dot VO_2 . Ec is taken to be a linear function of redox reduction and CB ventilatory drive. As Ec rises in hypoxia, the absolute potentials of each step in the citric acid cycle rises equally while the potential drop across each step remains constant because flux rate remains constant. A hypothetic HVRs ( dot VE vs SaO2) response curve computed from these assumptions is strikingly non linear. A hypothetic HVRp calculated from an assumed linear HVRs cannot be fit to the observed hyperbolic increase of ventilation in response to isocapnic hypoxia at PO2 less than 40 torr. The incompatibility of these results suggest that in future studies HVRs will not be found to be linear, especially below 80% SaO2 and HVRp will fail to be accurately hyperbolic.

  17. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition.

    Science.gov (United States)

    Do, Minchenko; Oo, Riabovol; Oo, Ratushna; Oh, Minchenko

    2017-01-01

    The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation. The expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more significant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes

  18. Characterization and Optimization of Polymer-Ceramic Pressure-Sensitive Paint by Controlling Polymer Content

    Directory of Open Access Journals (Sweden)

    Hitoshi Ishikawa

    2011-07-01

    Full Text Available A pressure-sensitive paint (PSP with fast response characteristics that can be sprayed on a test article is studied. This PSP consists of a polymer for spraying and a porous particle for providing the fast response. We controlled the polymer content (% from 10 to 90% to study its effects on PSP characteristics: the signal level, pressure sensitivity, temperature dependency, and time response. The signal level and temperature dependency shows a peak in the polymer content around 50 to 70%. The pressure sensitivity was fairly constant in the range between 0.8 and 0.9 %/kPa. The time response is improved by lowering the polymer content. The variation of the time response is shown to be on the order of milliseconds to ten seconds. A weight coefficient is introduced to optimize the resultant PSPs. By setting the weight coefficient, we can optimize the PSP for sensing purposes.

  19. Pseudo working-point control measurement scheme for acoustic sensitivity of interferometric fiber-optic hydrophones

    Institute of Scientific and Technical Information of China (English)

    Zefeng Wang; Yongming Hu; Zhou Meng; Ming Ni

    2008-01-01

    A novel pseudo working-point control measurement scheme for the acoustic sensitivity of interferometric fiber-optic hydrophones is described and demonstrated.The measurement principle is introduced in detail.An experimental system,which interrogates an interferometric fiber-optic hydrophone with this method,is designed.The acoustic pressure phase sensitivity of the fiber-optic hydrophone is measured over the frequency range of 20-2500Hz.The measured acoustic sensitivity is about-156.5dB re 1rad/μPa with a fluctuation lower than ±1.2dB,which is in good agreement with the results obtained by the method of phase generated carrier.The experimental results testify the validity of this new method which has the advantages of no electric elements in the sensing head,the simplicity of signal processing,and wide working bandwidth.

  20. Control of a velocity-sensitive audio-band quantum non-demolition interferometer

    CERN Document Server

    Leavey, S S; Gläfke, A; Barr, B W; Bell, A S; Gräf, C; Hennig, J -S; Houston, E A; Huttner, S H; Lück, H; Pascucci, D; Somiya, K; Sorazu, B; Spencer, A; Steinlechner, S; Strain, K A; Wright, J; Zhang, T; Hild, S

    2016-01-01

    The Sagnac speed meter interferometer topology can potentially provide enhanced sensitivity to gravitational waves in the audio-band compared to equivalent Michelson interferometers. A challenge with the Sagnac speed meter interferometer arises from the intrinsic lack of sensitivity at low frequencies where the velocity-proportional signal is smaller than the noise associated with the sensing of the signal. Using as an example the on-going proof-of-concept Sagnac speed meter experiment in Glasgow, we quantify the problem and present a solution involving the extraction of a small displacement-proportional signal. This displacement signal can be combined with the existing velocity signal to enhance low frequency sensitivity, and we derive optimal filters to accomplish this for different signal strengths. We show that the extraction of the displacement signal for low frequency control purposes can be performed without reducing significantly the quantum non-demolition character of this type of interferometer.

  1. Computational Fluid Dynamics Based Investigation of Sensitivity of Furnace Operational Conditions to Burner Flow Controls

    Energy Technology Data Exchange (ETDEWEB)

    Marc Cremer; Dave Wang; Connie Senior; Andrew Chiodo; Steven Hardy; Paul Wolff

    2005-07-01

    This is the Final Technical Report for DOE Cooperative Agreement No: DE-FC26-02NT41580. The goal of this project was to systematically assess the sensitivity of furnace operational conditions to burner air and fuel flows in coal fired utility boilers. The focus of this project was to quantify the potential impacts of ''fine level'' controls rather than that of ''coarse level'' controls (i.e. combustion tuning). Although it is well accepted that combustion tuning will generally improve efficiency and emissions of an ''out of tune'' boiler, it is not as well understood what benefits can be derived through active multiburner measurement and control systems in boiler that has coarse level controls. The approach used here was to utilize existing baseline furnace models that have been constructed using Reaction Engineering International's (REI) computational fluid dynamics (CFD) software. Using CFD analyses provides the ability to carry out a carefully controlled virtual experiment to characterize the sensitivity of NOx emissions, unburned carbon (UBC), furnace exit CO (FECO), furnace exit temperature (FEGT), and waterwall deposition to burner air and fuel flow rates. The Electric Power Research Institute (EPRI) provided co-funding for this program, and instrument and controls experts from EPRI's Instrument and Controls (I&C) Center have been active participants in this project. CFD simulations were completed for five coal fired boilers as planned: (1) 150 MW wall fired, (2) 500 MW opposed wall fired, (3) 600 MW T-Fired, (4) 330 MW cyclone-fired, and (5) 200 MW T-Fired Twin Furnace. In all cases, the unit selections were made in order to represent units that were descriptive of the utility industry as a whole. For each unit, between 25 and 44 furnace simulations were completed in order to evaluate impacts of burner to burner variations in: (1) coal and primary air flow rate, and (2) secondary air flow

  2. UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Sanming Deng

    Full Text Available The Crosstalk between a tumor and its hypoxic microenvironment has become increasingly important. However, the exact role of UCP2 function in cancer cells under hypoxia remains unknown. In this study, UCP2 showed anti-apoptotic properties in A549 cells under hypoxic conditions. Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS accumulation (P<0.001 and apoptosis (P<0.001 compared to the controls when the cells were exposed to hypoxia. Moreover, over-expression of UCP2 inhibited the release of cytochrome C and reduced the activation of caspase-9. Conversely, suppression of UCP2 resulted in the ROS generation (P = 0.006, the induction of apoptosis (P<0.001, and the release of cytochrome C from mitochondria to the cytosolic fraction, thus activating caspase-9. These data suggest that over-expression of UCP2 has anti-apoptotic properties by inhibiting ROS-mediated apoptosis in A549 cells under hypoxic conditions.

  3. Effect of high-intensity hypoxic training on sea-level swimming performances.

    Science.gov (United States)

    Truijens, M J; Toussaint, H M; Dow, J; Levine, B D

    2003-02-01

    The objective of this study was to test the hypothesis that high-intensity hypoxic training improves sea-level performances more than equivalent training in normoxia. Sixteen well-trained collegiate and Masters swimmers (10 women, 6 men) completed a 5-wk training program, consisting of three high-intensity training sessions in a flume and supplemental low- or moderate-intensity sessions in a pool each week. Subjects were matched for gender, performance level, and training history, and they were assigned to either hypoxic [Hypo; inspired O2 fraction (Fi(O(2))) = 15.3%, equivalent to a simulated altitude of 2,500 m] or normoxic (Norm; Fi(O(2)) = 20.9%) interval training in a randomized, double-blind, placebo-controlled design. All pool training occurred under Norm conditions. The primary performance measures were 100- and 400-m freestyle time trials. Laboratory outcomes included maximal O(2) uptake (Vo(2 max)), anaerobic capacity (accumulated O(2) deficit), and swimming economy. Significant (P = 0.02 and swimming performances and Vo(2 max) in well-trained swimmers, with no additive effect of hypoxic training.

  4. Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death.

    Science.gov (United States)

    Guven, A; Ickin, M; Uzun, O; Bakar, C; Balbay, E Gulec; Balbay, O

    2014-02-01

    The purpose of this study was to examine the effects of hypobaric hypoxia on testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and hypoxia-inducible factor 1α expressions were detected by immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic chamber. Rats in the erdosteine group were exposed to the same conditions and treated orally with erdosteine (20 mg kg(-1) daily) at the same time from the first day of hypoxic exposure for 2 weeks. The normoxia group was evaluated as the control. The hypoxia group showed decreased height of spermatogenic epithelium in some seminiferous tubules, vacuolisation in spermatogenic epithelial cells, deterioration and gaps in the basal membrane and an increase in blood vessels in the interstitial area. The erdosteine group showed amelioration of both epithelial cell vacuolisation and basal membrane deterioration. Numbers of hypoxia-inducible factor 1α-immunostained Sertoli and Leydig cells were significantly higher in the hypoxia group than in the erdosteine group. The number of seminiferous tubules with caspase-3-immunostained germ cells was highest in the hypoxia group and decreased in the erdosteine and normoxia groups respectively. Based on these observations, erdosteine protects testis tissue from hypoxic injury by reducing apoptotic cell death.

  5. Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

    Directory of Open Access Journals (Sweden)

    G. A. Karkashadze

    2016-01-01

    Full Text Available Hypoxic-ischemic brain lesions in children are the main environmental (non-genetic factor in forming severe neurological pathology with subsequent disability. Scientists see the improvement of therapeutic approaches in acute phase of the disease as a main way to reduce the severity of neurologic complications. Due to the achievements in neuroscience in the field of perinatal hypoxicischemic injury mechanisms, three energy phases of pathologic events deployment were identified: primary (up to 6 hours from the lesion, secondary (6 to 24–48 h after the lesion and distal tertiary (during few weeks, months. At the same time, necrosis, apoptosis, glutamate excitotoxicity, oxidative stress, inflammation, angiogenesis and neurogenesis make up separate links of destruction process. On the basis of new data on the pathogenesis of the disease, scientists from different countries have already offered modern treatment methods for perinatal hypoxic-ischemic injury with erythropoietin, allopurinol, melatonin, N-acetylcysteine, magnesium sulphate, albumin, -interferon, as well as with the help of controlled hypothermia, xenon, the use of stem cells, etc. This article presents a review of new data on pathogenesis and promising treatment methods for perinatal hypoxic-ischemic injuries.

  6. An Argonaute 2 Switch Regulates Circulating miR-210 to Coordinate Hypoxic Adaptation across Cells

    Science.gov (United States)

    Hale, Andrew; Lee, Changjin; Annis, Sofia; Min, Pil-Ki; Pande, Reena; Creager, Mark A.; Julian, Colleen G.; Moore, Lorna G.; Mitsialis, S. Alex; Hwang, Sarah J.; Kourembanas, Stella; Chan, Stephen Y.

    2014-01-01

    Complex organisms may coordinate molecular responses to hypoxia by specialized avenues of communication across multiple tissues, but these mechanisms are poorly understood. Plasma-based, extracellular microRNAs have been described, yet, their regulation and biological functions in hypoxia remain enigmatic. We found a unique pattern of release of the hypoxia-inducible microRNA-210 (miR-210) from hypoxic and reoxygenated cells. This microRNA is also elevated in human plasma in physiologic and pathologic conditions of altered oxygen demand and delivery. Released miR-210 can be delivered to recipient cells, and its direct suppression of its direct target ISCU and mitochondrial metabolism is primarily evident in hypoxia. To regulate these hypoxia-specific actions, prolyl-hydroxylation of Argonaute 2 acts as a molecular switch that reciprocally modulates miR-210 release and intracellular activity in source cells as well as regulates intracellular activity in recipient cells after miR-210 delivery. Therefore, Argonaute 2-dependent control of released miR-210 represents a unique communication system that integrates the hypoxic response across anatomically distinct cells, preventing unnecessary activity of delivered miR-210 in normoxia while still preparing recipient tissues for incipient hypoxic stress and accelerating adaptation. PMID:24983771

  7. Identification and control of dissolved oxygen in hybridoma cell culture in a shear sensitive environment.

    Science.gov (United States)

    Simon, L; Karim, M N

    2001-01-01

    The productivity of mammalian cells can be enhanced by facilitating adequate oxygen transfer into the cultivation medium. However, current methods of controlling dissolved oxygen (DO) fail to account for alterations in medium composition during the course of the fermentation. These changes, which directly affect gas solubility and overall mass transfer coefficient, may be significant and deteriorate controller's performance in the long run. In this paper, the applications of Generalized Predictive Controllers (GPC) to DO control were investigated in a shear sensitive environment and compared to PID and Model Predictive Controllers (MPC). Input and output data for system identification were initially generated by varying the composition of oxygen fed into the bioreactor from 0 to 0.21 mol % while keeping the total inlet gas flow rate at 8.75 vvm. The process was identified using an AutoRegressive model with eXogeneous inputs (ARX) model and tested on different data sets. The model parameters were then correlated with the overall mass transfer coefficients. In simulation tests, the output of the PID controller switched from minimum to maximum values while more continuous control signals were obtained with the MPC and GPC controllers. When tested in a cell-free medium, all three controllers were able to track setpoint changes with some chattering observed in the control signals. The GPC outperformed the MPC and PID controllers when applied to the cultivation of hybridoma cells.

  8. Mapping Drought Sensitivity of Ecosystem Functioning in Mountainous Watersheds: Spatial Heterogeneity and Geological-Geomorphological Control

    Science.gov (United States)

    Wainwright, H. M.; Steefel, C. F.; Williams, K. H.; Hubbard, S. S.; Enquist, B. J.; Steltzer, H.; Sarah, T.

    2016-12-01

    Mountainous watersheds in the Upper Colorado River Basin play a critical role in supplying water and nutrients to western North America. Ecosystem functioning in those regions - including plant dynamics and biogeochemical cycling - is known to be limited by water availability. Under the climate change, early snowmelt and increasing temperature are expected to intensify the drought conditions in early growing seasons. Although the impact of early-season drought has been documented in plot-scale experiments, ascertaining its significance in mountainous watersheds is challenging given the highly heterogeneous nature of the systems with complex terrain and diverse plant functional types (PFTs). The objectives of this study are (1) to map the regions where the plant dynamics are relatively more sensitive to drought conditions based on historical satellite and climate data, and (2) to identify the environmental controls (e.g., geomorphology, elevation, geology, snow and PFT) on drought sensitivity. We characterize the spatial heterogeneity of drought sensitivity in four watersheds (a 15 x 15 km domain) near the Rocky Mountain Biological Laboratory in Colorado, USA. Following previous plot-scale studies, we first define the drought sensitivity based on annual peak NDVI (Landsat 5) and climatic datasets. Non-parametric tree-based machine learning methods are used to identify the significant environmental controls, using high-resolution LiDAR digital elevation map and peak snow-water-equivalent distribution from NASA airborne snow observatory. Results show that the drought sensitivity is negatively correlated with elevation, suggesting increased water limitations in lower elevation (less snow, higher temperature). The drought sensitivity is more spatially variable in shallow-rooted plant types, affected by local hydrological conditions. We also found geomorphological and geological controls, such as high sensitivity in the steep well-drained glacial moraine regions. Our

  9. Executive control over unconscious cognition: Attentional sensitization of unconscious information processing

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    Markus eKiefer

    2012-03-01

    Full Text Available Unconscious priming is a prototypical example of an automatic process, which is initiated without deliberate intention. Classical theories of automaticity assume that such unconscious automatic processes occur in a purely bottom-up driven fashion independent of attentional control mechanisms. In contrast to these classical theories, our attentional sensitization model of unconscious information processing proposes that unconscious processing is susceptible to attentional top-down control and is only elicited if the cognitive system is configured accordingly. It is assumed that unconscious processing depends on attentional amplification of task-congruent processing pathways. This article provides an overview of the latest research on executive control influences on unconscious information processing. I introduce refined theories of automaticity with a particular focus on the attentional sensitization model of unconscious cognition which is specifically developed to account for various attentional influences on different types of unconscious information processing. In support of the attentional sensitization model, empirical evidence is reviewed demonstrating attentional top-down influences on unconscious cognition in the domains of visuo-motor, semantic and emotional processing: Subliminal priming depends on attentional resources, is susceptible to stimulus expectations and is influenced by action intentions and task sets. This suggests that even unconscious processing is flexible and context-dependent as a function of higher-level executive control settings. It is discussed that the assumption of attentional sensitization of unconscious information processing can accommodate conflicting findings regarding the automaticity of processes in many areas. This theoretical view has the potential to stimulate future research on the cognitive control of unconscious processing in healthy and clinical populations.

  10. Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia.

    Science.gov (United States)

    Faiss, Raphaël; Girard, Olivier; Millet, Grégoire P

    2013-12-01

    Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea level but train under hypoxic conditions, has gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic' or 'anaerobic' interval training, it is believed that IHT would potentiate greater performance improvements compared to similar training at sea level. A thorough analysis of studies including IHT, however, leads to strikingly poor benefits for sea-level performance improvement, compared to the same training method performed in normoxia. Despite the positive molecular adaptations observed after various IHT modalities, the characteristics of optimal training stimulus in hypoxia are still unclear and their functional translation in terms of whole-body performance enhancement is minimal. To overcome some of the inherent limitations of IHT (lower training stimulus due to hypoxia), recent studies have successfully investigated a new training method based on the repetition of short (training in hypoxia (RSH). The aims of the present review are therefore threefold: first, to summarise the main mechanisms for interval training and repeated sprint training in normoxia. Second, to critically analyse the results of the studies involving high-intensity exercises performed in hypoxia for sea-level performance enhancement by differentiating IHT and RSH. Third, to discuss the potential mechanisms underpinning the effectiveness of those methods, and their inherent limitations, along with the new research avenues surrounding this topic.

  11. SQP-methods for solving optimal control problems with control and state constraints: adjoint variables, sensitivity analysis and real-time control

    Science.gov (United States)

    Büskens, Christof; Maurer, Helmut

    2000-08-01

    Parametric nonlinear optimal control problems subject to control and state constraints are studied. Two discretization methods are discussed that transcribe optimal control problems into nonlinear programming problems for which SQP-methods provide efficient solution methods. It is shown that SQP-methods can be used also for a check of second-order sufficient conditions and for a postoptimal calculation of adjoint variables. In addition, SQP-methods lead to a robust computation of sensitivity differentials of optimal solutions with respect to perturbation parameters. Numerical sensitivity analysis is the basis for real-time control approximations of perturbed solutions which are obtained by evaluating a first-order Taylor expansion with respect to the parameter. The proposed numerical methods are illustrated by the optimal control of a low-thrust satellite transfer to geosynchronous orbit and a complex control problem from aquanautics. The examples illustrate the robustness, accuracy and efficiency of the proposed numerical algorithms.

  12. Assessing the impact of revegetation and weed control on urban sensitive bird species.

    Science.gov (United States)

    Archibald, Carla L; McKinney, Matthew; Mustin, Karen; Shanahan, Danielle F; Possingham, Hugh P

    2017-06-01

    Nature in cities is concentrated in urban green spaces, which are key areas for urban biodiversity and also important areas to connect people with nature. To conserve urban biodiversity within these natural refugia, habitat restoration such as weed control and revegetation is often implemented. These actions are expected to benefit biodiversity, although species known to be affected by urbanization may not be interacting with restoration in the ways we anticipate. In this study, we use a case study to explore how urban restoration activities impact different bird species. Birds were grouped into urban sensitivity categories and species abundance, and richness was then calculated using a hierarchical species community model for individual species responses, with "urban class" used as the hierarchical parameter. We highlight variable responses of birds to revegetation and weed control based on their level of urban sensitivity. Revegetation of open grassy areas delivers significant bird conservation outcomes, but the effects of weed control are neutral or in some cases negative. Specifically, the species most reliant on remnant vegetation in cities seem to remain stable or decline in abundance in areas with weed control, which we suspect is the result of a simplification of the understorey. The literature reports mixed benefits of weed control between taxa and between locations. We recommend, in our case study site, that weed control be implemented in concert with replanting of native vegetation to provide the understory structure preferred by urban sensitive birds. Understanding the impacts of revegetation and weed control on different bird species is important information for practitioners to make restoration decisions about the allocation of funds for conservation action. This new knowledge can be used both for threatened species and invasive species management.

  13. CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells.

    Science.gov (United States)

    Llobet, D; Eritja, N; Encinas, M; Llecha, N; Yeramian, A; Pallares, J; Sorolla, A; Gonzalez-Tallada, F J; Matias-Guiu, X; Dolcet, X

    2008-04-17

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising antineoplastic agent because of its ability to selectively kill tumoral cells. However, some cancer cells are resistant to TRAIL-induced apoptosis. We have previously demonstrated that in endometrial carcinoma cells such resistance is caused by elevated FLICE-inhibitory protein (FLIP) levels. The present study focuses on the mechanisms by which FLIP could be modulated to sensitize endometrial carcinoma cells to TRAIL-induced apoptosis. We find that inhibition of casein kinase (CK2) sensitizes endometrial carcinoma cells to TRAIL- and Fas-induced apoptosis. CK2 inhibition correlates with a reduction of FLIP protein, suggesting that CK2 regulates resistance to TRAIL and Fas by controlling FLIP levels. FLIP downregulation correlates with a reduction of mRNA and is prevented by addition of the MG-132, suggesting that CK2 inhibition results in a proteasome-mediated degradation of FLIP. Consistently, forced expression of FLIP restores resistance to TRAIL and Fas. Moreover, knockdown of either FADD or caspase-8 abrogates apoptosis triggered by inhibition of CK2, indicating that CK2 sensitization requires formation of functional DISC. Finally, because of the possible role of both TRAIL and CK2 in cancer therapy, we demonstrate that CK2 inhibition sensitizes primary endometrial carcinoma explants to TRAIL apoptosis. In conclusion, we demonstrate that CK2 regulates endometrial carcinoma cell sensitivity to TRAIL and Fas by regulating FLIP levels.

  14. Genetic control of lithium sensitivity and regulation of inositol biosynthetic genes.

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    Jason King

    Full Text Available Lithium (Li(+ is a common treatment for bipolar mood disorder, a major psychiatric illness with a lifetime prevalence of more than 1%. Risk of bipolar disorder is heavily influenced by genetic predisposition, but is a complex genetic trait and, to date, genetic studies have provided little insight into its molecular origins. An alternative approach is to investigate the genetics of Li(+ sensitivity. Using the social amoeba Dictyostelium, we previously identified prolyl oligopeptidase (PO as a modulator of Li(+ sensitivity. In a link to the clinic, PO enzyme activity is altered in bipolar disorder patients. Further studies demonstrated that PO is a negative regulator of inositol(1,4,5trisphosphate (IP(3 synthesis, a Li(+ sensitive intracellular signal. However, it was unclear how PO could influence either Li(+ sensitivity or risk of bipolar disorder. Here we show that in both Dictyostelium and cultured human cells PO acts via Multiple Inositol Polyphosphate Phosphatase (Mipp1 to control gene expression. This reveals a novel, gene regulatory network that modulates inositol metabolism and Li(+ sensitivity. Among its targets is the inositol monophosphatase gene IMPA2, which has also been associated with risk of bipolar disorder in some family studies, and our observations offer a cellular signalling pathway in which PO activity and IMPA2 gene expression converge.

  15. Habituation and sensitization to heat and cold pain in women with fibromyalgia and healthy controls.

    Science.gov (United States)

    Smith, Bruce W; Tooley, Erin M; Montague, Erica Q; Robinson, Amanda E; Cosper, Cynthia J; Mullins, Paul G

    2008-12-01

    The purpose of this study was to examine differences in habituation to heat and cold pain in women with fibromyalgia (FM; n=33) and in women who were healthy controls (HC; n=44). Quantitative sensory testing (QST) was used to assess pain thresholds during five consecutive trials of ascending heat and descending cold stimulation. Anxiety, depression, fatigue, and pain during the previous week were assessed using self-report measures. The overall hypotheses were that there would be differences between groups in pain thresholds and in the rate of habituation to heat and cold pain stimuli. Multilevel modeling was used to test the hypotheses. There were large overall differences in pain thresholds, with the FM group showing greater sensitivity to heat and cold pain stimuli compared with the HC group. While habituation occurred in both of the groups for heat pain, the HC group had stronger habituation across trials than the FM group. Conversely, while the HC group habituated to cold pain stimuli, the FM group showed sensitization and had decreased cold pain thresholds across trials (they felt cold pain at higher temperatures). In addition, anxiety, depression, fatigue, and pain were related to decreased heat and cold pain thresholds in the overall sample. However, when group was controlled, none of these variables were related to thresholds or rates of habituation or sensitization. The differences between women with FM and healthy women in habituation and sensitization may have important implications for the etiology, diagnosis, and treatment of FM and other chronic pain conditions.

  16. Ca2+ cytochemical changes of hepatotoxicity caused by halothane and sevoflurane in enzyme-induced hypoxic rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Feng Yu; Li-Qun Yang; Mai-Tao Zhou; Zhi-Qiang Liu; Quan Li

    2005-01-01

    AIM: To investigat the relation between hepatotoxicity of halothane and sevoflurane and altered hepatic calcium homeostasis in enzyme-induced hypoxic rats.METHODS: Forty-eight rats were pretreated with phenobarbital and randomly divided into six groups (eight in each group) and exposed to O2/N2/1.2 MAC anesthetics for :1 h: normal control (NC), 21% O2/79% N2; hypoxic control (HC), 14% O2/86%N2; normal sevoflurane (NS),21% O2/ N2/1.2MAC sevoflurane; hypoxic sevoflurane (HS), 14% O2/N2/1.2MAC sevoflurane; normal halothane (NH)21%O2/7g%N2/1.2MAC halothane; hypoxic halothane (HH), 14% O2/N2/1.2MAC halothane. Liver specimens and blood were taken 24 h after exposure to calcium and determined by EDX microanalysis.RESULTS: The liver of all rats given halothane (14%O2)had extensive centrilobular necrosis and denaturation.Morphologic damage was accompanied with an increase in serum glutamic pyruvic transminase. In groups NH and HH, more calcium was precipitated in cytoplasm and mitochondria.CONCLUSION: These results suggest that halothane increases cytosolic Ca2+ concentration in hepatocytes.Elevation in Ca2+ concentration is implicated in the mechanism of halothane-induced hepatotoxicity.sevoflurane is less effective in affecting hepatic calcium homeostasis than halothane.

  17. Effect of L-Arginine on Pulmonary Artery Smooth Muscle Cell Apoptosis in Rats with Hypoxic Pulmonary Vascular Structural Remodeling

    Institute of Scientific and Technical Information of China (English)

    Ingrid Karmane SUMOU; Jun-Bao DU; Bing WEI; Chun-Yu ZHANG; Jian-Guang QI; Chao-Shu TANG

    2006-01-01

    This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatebiotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

  18. PUMA-mediated mitochondrial apoptotic disruption by hypoxic postconditioning.

    Science.gov (United States)

    Li, YuZhen; Guo, Qi; Liu, XiuHua; Wang, Chen; Song, DanDan

    2015-08-01

    Postconditioning can reduce ischemia-reperfusion (I/R)-induced cardiomyocyte apoptosis by targeting mitochondria. p53 upregulated modulator of apoptosis (PUMA) is involved in lethal I/R injury. Here, we hypothesized that postconditioning might inhibit mitochondrial pathway-mediated cardiomyocyte apoptosis by controlling PUMA expression. The cultured neonatal rat cardiomyocytes underwent 3 h of hypoxia and 3 h of reoxygenation. Postconditioning consisted of three cycles of 5 min reoxygenation and 5 min hypoxia after prolonged hypoxia. Hypoxic postconditioning reduced the levels of PUMA mRNA and protein. Concomitantly, the loss of mitochondrial membrane potential, cytochrome c release and caspase-3 activation were decreased significantly by postconditioning. Overexpression of PUMA increased greatly not only the number of apoptotic cardiomyocytes, but also the collapse of mitochondrial membrane potential, cytochrome c release and caspase-3 activation under postconditioning condition. The data suggest that reduction of PUMA expression mediates the endogenous cardioprotective mechanisms of postconditioning by disrupting mitochondrial apoptotic pathway.

  19. Computational Fluid Dynamics Based Investigation of Sensitivity of Furnace Operational Conditions to Burner Flow Controls

    Energy Technology Data Exchange (ETDEWEB)

    Marc Cremer; Kirsi St. Marie; Dave Wang

    2003-04-30

    This is the first Semiannual Technical Report for DOE Cooperative Agreement No: DE-FC26-02NT41580. The goal of this project is to systematically assess the sensitivity of furnace operational conditions to burner air and fuel flows in coal fired utility boilers. Our approach is to utilize existing baseline furnace models that have been constructed using Reaction Engineering International's (REI) computational fluid dynamics (CFD) software. Using CFD analyses provides the ability to carry out a carefully controlled virtual experiment to characterize the sensitivity of NOx emissions, unburned carbon (UBC), furnace exit CO (FECO), furnace exit temperature (FEGT), and waterwall deposition to burner flow controls. The Electric Power Research Institute (EPRI) is providing co-funding for this program, and instrument and controls experts from EPRI's Instrument and Controls (I&C) Center are active participants in this project. This program contains multiple tasks and good progress is being made on all fronts. A project kickoff meeting was held in conjunction with NETL's 2002 Sensors and Control Program Portfolio Review and Roadmapping Workshop, in Pittsburgh, PA during October 15-16, 2002. Dr. Marc Cremer, REI, and Dr. Paul Wolff, EPRI I&C, both attended and met with the project COR, Susan Maley. Following the review of REI's database of wall-fired coal units, the project team selected a front wall fired 150 MW unit with a Riley Low NOx firing system including overfire air for evaluation. In addition, a test matrix outlining approximately 25 simulations involving variations in burner secondary air flows, and coal and primary air flows was constructed. During the reporting period, twenty-two simulations have been completed, summarized, and tabulated for sensitivity analysis. Based on these results, the team is developing a suitable approach for quantifying the sensitivity coefficients associated with the parametric tests. Some of the results of the CFD

  20. A common control group - optimising the experiment design to maximise sensitivity.

    Directory of Open Access Journals (Sweden)

    Simon Bate

    Full Text Available Methods for choosing an appropriate sample size in animal experiments have received much attention in the statistical and biological literature. Due to ethical constraints the number of animals used is always reduced where possible. However, as the number of animals decreases so the risk of obtaining inconclusive results increases. By using a more efficient experimental design we can, for a given number of animals, reduce this risk. In this paper two popular cases are considered, where planned comparisons are made to compare treatments back to control and when researchers plan to make all pairwise comparisons. By using theoretical and empirical techniques we show that for studies where all pairwise comparisons are made the traditional balanced design, as suggested in the literature, maximises sensitivity. For studies that involve planned comparisons of the treatment groups back to the control group, which are inherently more sensitive due to the reduced multiple testing burden, the sensitivity is maximised by increasing the number of animals in the control group while decreasing the number in the treated groups.

  1. Long-lasting changes in DNA methylation following short-term hypoxic exposure in primary hippocampal neuronal cultures.

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    Iain Hartley

    Full Text Available While the effects of hypoxia on gene expression have been investigated in the CNS to some extent, we currently do not know what role epigenetics plays in the transcription of many genes during such hypoxic stress. To start understanding the role of epigenetic changes during hypoxia, we investigated the long-term effect of hypoxia on gene expression and DNA methylation in hippocampal neuronal cells. Primary murine hippocampal neuronal cells were cultured for 7 days. Hypoxic stress of 1% O2, 5% CO2 for 24 hours was applied on Day 3, conditions we found to maximize cellular hypoxic stress response without inducing cell death. Cells were returned to normoxia for 4 days following the period of hypoxic stress. On Day 7, Methyl-Sensitive Cut Counting (MSCC was used to identify a genome-wide methylation profile of the hippocampal cell lines to assess methylation changes resulting from hypoxia. RNA-Seq was also done on Day 7 to analyze changes in gene transcription. Phenotypic analysis showed that neuronal processes were significantly shorter after 1 day of hypoxia, but there was a catch-up growth of these processes after return to normoxia. Transcriptome profiling using RNA-Seq revealed 369 differentially expressed genes with 225 being upregulated, many of which form networks shown to affect CNS development and function. Importantly, the expression level of 59 genes could be correlated to the changes in DNA methylation in their promoter regions. CpG islands, in particular, had a strong tendency to remain hypomethylated long after hypoxic stress was removed. From this study, we conclude that short-term, sub-lethal hypoxia results in long-lasting changes to genome wide DNA methylation status and that some of these changes can be highly correlated with transcriptional modulation in a number of genes involved in functional pathways that have been previously implicated in neural growth and development.

  2. Metabolic adaptations may counteract ventilatory adaptations of intermittent hypoxic exposure during submaximal exercise at altitudes up to 4000 m.

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    Martin Faulhaber

    Full Text Available Intermittent hypoxic exposure (IHE has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7 × 1 hour at 4500 m. The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05. There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = -0.72, p<0.05. Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01 and minute ventilation (r = 0.54, p<0.01. Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.

  3. Contextually sensitive power changes across multiple frequency bands underpin cognitive control.

    Science.gov (United States)

    Cooper, Patrick S; Darriba, Álvaro; Karayanidis, Frini; Barceló, Francisco

    2016-05-15

    Flexible control of cognition bestows a remarkable adaptability to a broad range of contexts. While cognitive control is known to rely on frontoparietal neural architecture to achieve this flexibility, the neural mechanisms that allow such adaptability to context are poorly understood. In the current study, we quantified contextual demands on the cognitive control system via a priori estimation of information across three tasks varying in difficulty (oddball, go/nogo, and switch tasks) and compared neural responses across these different contexts. We report evidence of the involvement of multiple frequency bands during preparation and implementation of cognitive control. Specifically, a common frontoparietal delta and a central alpha process corresponded to rule implementation and motor response respectively. Interestingly, we found evidence of a frontal theta signature that was sensitive to increasing amounts of information and a posterior parietal alpha process only seen during anticipatory rule updating. Importantly, these neural signatures of context processing match proposed frontal hierarchies of control and together provide novel evidence of a complex interplay of multiple frequency bands underpinning flexible, contextually sensitive cognition.

  4. Hypoxic training methods for improving endurance exercise performance

    Directory of Open Access Journals (Sweden)

    Jacob A. Sinex

    2015-12-01

    Full Text Available Endurance athletic performance is highly related to a number of factors that can be altered through altitude and hypoxic training including increases in erythrocyte volume, maximal aerobic exercise capacity, capillary density, and economy. Physiological adaptations in response to acute and chronic exposure to hypoxic environments are well documented and range from short-term detrimental effects to longer-term adaptations that can improve performance at altitude and in sea-level competitions. Many altitude and hypoxic training protocols have been developed, employing various combinations of living and training at sea-level, low, moderate, and high altitudes and utilizing natural and artificial altitudes, with varying degrees of effectiveness. Several factors have been identified that are associated with individual responses to hypoxic training, and techniques for identifying those athletes most likely to benefit from hypoxic training continue to be investigated. Exposure to sufficiently high altitude (2000–3000 m for more than 12 h/day, while training at lower altitudes, for a minimum of 21 days is recommended. Timing of altitude training related to competition remains under debate, although general recommendations can be considered.

  5. A low protein diet increases the hypoxic tolerance in Drosophila.

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    Paul Vigne

    Full Text Available Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2 and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.

  6. NLP-1: a DNA intercalating hypoxic cell radiosensitizer and cytotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Panicucci, R.; Heal, R.; Laderoute, K.; Cowan, D.; McClelland, R.A.; Rauth, A.M.

    1989-04-01

    The 2-nitroimidazole linked phenanthridine, NLP-1 (5-(3-(2-nitro-1-imidazoyl)-propyl)-phenanthridinium bromide), was synthesized with the rationale of targeting the nitroimidazole to DNA via the phenanthridine ring. The drug is soluble in aqueous solution (greater than 25 mM) and stable at room temperature. It binds to DNA with a binding constant 1/30 that of ethidium bromide. At a concentration of 0.5 mM, NLP-1 is 8 times more toxic to hypoxic than aerobic cells at 37 degrees C. This concentration is 40 times less than the concentration of misonidazole, a non-intercalating 2-nitroimidazole, required for the same degree of hypoxic cell toxicity. The toxicity of NLP-1 is reduced at least 10-fold at 0 degrees C. Its ability to radiosensitize hypoxic cells is similar to misonidazole at 0 degrees C. Thus the putative targeting of the 2-nitroimidazole, NLP-1, to DNA, via its phenanthridine group, enhances its hypoxic toxicity, but not its radiosensitizing ability under the present test conditions. NLP-1 represents a lead compound for intercalating 2-nitroimidazoles with selective toxicity for hypoxic cells.

  7. The Relationship between Plasma Endothelin and Hypoxic- Ischemic Encephalopathy in 70 Tibetan Neonates of Plateau Area

    Institute of Scientific and Technical Information of China (English)

    DEJI Meiduo; ZHAO Rong; ZHAO Min; WU Sulan

    2002-01-01

    Objective To discuss the dynamic changing characteristics of plasma endothelin in Tibetan neonates of plateau area with hypoxic - ischemic encephalopathy. Methods Plasma ET level has been determined for 10 days 72 hours after birth by radioimmunoassay in 70 tibetan neonates with HIE.The control group consisted of 20 healthy neonates. Results During acute stage, plasma ET levels of mild, moderate and severe groups were significantly higher that of control group (P < 0.001 ). During acute stage, plasma ET level was closely related with the severity of HIE. Severer HIE was, higher ET level. Conclusion ET was involved in the regulation of HIE.

  8. Thyroid and hypoxic stress in the newt Triturus carnifex.

    Science.gov (United States)

    Frangioni, Giuliano; Atzori, Antonio; Balzi, Manuela; Fuzzi, Giancarlo; Ghinassi, Andrea; Pescosolido, Nicoletta; Bianchi, Stefano; Borgioli, Gianfranco

    2006-03-01

    When specimens of the newt Triturus carnifex, under anaesthesia by submersion in a 0.2% chlorbutol solution for 25 min, are isolated in a respiratory chamber at 18 degrees C containing water with only 1.3 ppm of oxygen, they consume the oxygen completely in about 3 hr, but they can stay alive for many more hours and wake up with no apparent exterior consequences. Hypoxia induces rapid onset of hepatic steatosis and melanosis, as well as a controlled haemolytic process involving a pool of red blood cells of the same order of size as that held as a reserve in the spleen by animals in an aerial habitat. At the origin of the phenomena is an intense response by the hypophysis, histologically detectable 1 hr from the onset of treatment and confirmed 2 hr later by a highly significant increase in the plasma thyroidstimulating hormone (TSH) concentration compared with the controls (41.5 +/- 13.7 microU/L vs. 15.5 +/- 6.2; P thyroid follicles react by reabsorbing their colloid, but instead of an increase in the plasma free T3 and T4 concentrations, fT3 falls significantly (1.5 +/- 0.3 pg/mL vs., the 2.4 +/- 0.7; P thyroid, gall bladder and gut result negative, and this does not agree with hypotheses of hormone inactivation by deiodination, sulphation or glucuronidation. This apparently peculiar endocrine path has not been observed in previous studies on hypoxia in vertebrates, because the experiments were always designed to analyse plasma hormone levels after at least 24 hr of hypoxia or during chronic treatments, losing the most interesting phases of the endocrine response. The possibility that the hypoxic newt possesses alternative or complementary metabolic pathways to anaerobic glycolysis to sustain steatogenesis and melanogenesis and maintain the same cardiac activity as the controls is briefly discussed. Copyright 2006 Wiley-Liss, Inc.

  9. Direct ELISA kits as a sensitive and selective screening method for abstinence control in urine.

    Science.gov (United States)

    Kirschbaum, Katrin M; Musshoff, Frank; Wilbert, Ansgar; Röhrich, Jörg; Madea, Burkhard

    2011-04-15

    In 2009 cutoff values of assessment criteria to testify abstinence control in order to estimate driving ability were standardized in Germany. The cutoff values are lower than required in existing guidelines like SAMHSA and there is critical discussion about detection of low concentrations by using immunoassay, especially concerning amphetamines in urine (50 ng/ml). In this study Direct ELISA kits were tested for their applicability to identify the absence of amphetamines, cannabinoids, opiates, cocaine, methadone and benzodiazepines in urine. Results were confirmed by LC/MS or GC/MS analyses. Sensitivity, specificity, predictive values (positive as well as negative) and overall misclassification rates were evaluated by contingency tables and were compared to ROC-analyses. Sensitivity results as well as specificity results were satisfying showing sensitivity values higher than 96% for each analyte. The amphetamine test we used showed sensitivity and specificity of 100% and 88%, respectively, even if amphetamine tests usually react with high cross-reactivity. Our study results include high discrimination at required cutoff values between positives and negatives for each drug group and demonstrate that immunological tests complying with requirements of current decreased urine cutoff values for assessment of driving ability do exist.

  10. Temperature sensitivity analysis of polarity controlled electrostatically doped tunnel field-effect transistor

    Science.gov (United States)

    Nigam, Kaushal; Pandey, Sunil; Kondekar, P. N.; Sharma, Dheeraj

    2016-09-01

    The conventional tunnel field-effect transistors (TFETs) have shown potential to scale down in sub-22 nm regime due to its lower sub-threshold slope and robustness against short-channel effects (SCEs), however, sensitivity towards temperature variation is a major concern. Therefore, for the first time, we investigate temperature sensitivity analysis of a polarity controlled electrostatically doped tunnel field-effect transistor (ED-TFET). Different performance metrics and analog/RF figure-of-merits were considered and compared for both devices, and simulations were performed using Silvaco ATLAS device tool. We found that the variation in ON-state current in ED-TFET is almost temperature independent due to electrostatically doped mechanism, while, it increases in conventional TFET at higher temperature. Above room temperature, the variation in ION, IOFF, and SS sensitivity in ED-TFET are only 0.11%/K, 2.21%/K, and 0.63%/K, while, in conventional TFET the variations are 0.43%/K, 2.99%/K, and 0.71%/K, respectively. However, below room temperature, the variation in ED-TFET ION is 0.195%/K compared to 0.27%/K of conventional TFET. Moreover, it is analysed that the incomplete ionization effect in conventional TFET severely affects the drive current and the threshold voltage, while, ED-TFET remains unaffected. Hence, the proposed ED-TFET is less sensitive towards temperature variation and can be used for cryogenics as well as for high temperature applications.

  11. The prevalence of ibuprofen-sensitive asthma in children: a randomized controlled bronchoprovocation challenge study.

    Science.gov (United States)

    Debley, Jason S; Carter, Edward R; Gibson, Ronald L; Rosenfeld, Margaret; Redding, Gregory J

    2005-08-01

    To determine the prevalence of ibuprofen-sensitive asthma in school-aged children with mild or moderate persistent asthma. A randomized, double-blind, placebo-controlled, crossover bronchoprovocation challenge study in children 6 to 18 years of age with mild or moderate persistent asthma. Patients received a single dose of ibuprofen or placebo, per randomization, and then returned 2 to 7 days later to repeat the procedures after taking that study drug not received at the first visit. At each visit, patients performed spirometry before and (1/2), 1, 2, and 4 hours after administration of study drug. We defined bronchospasm as a > or =20% decrease from baseline in the forced expired volume in the first second (FEV1) and ibuprofen sensitivity as bronchospasm following administration of ibuprofen but not placebo. Of the 127 patients screened, 100 (mean age, 11 years) completed the study. Two patients met criteria for ibuprofen-sensitive asthma, resulting in a prevalence of 2% (95% CI: 0.2%-7%). Neither patient was known to have had any exposure to ibuprofen before the study. The prevalence of ibuprofen-sensitive asthma was low but non-zero in this group of children with mild or moderate asthma. The possibility of ibuprofen-induced bronchospasm should be considered before administering ibuprofen to children with asthma.

  12. [Role of heat-shock proteins of Hsp70 family in changes of narcotic activity of hyperbaric nitrogen during increasing hypoxic stimulus].

    Science.gov (United States)

    Vetosh, A N; Kostkin, V B; Alekseeva, O A; Korzhevskiĭ, D E

    2008-01-01

    The spontaneous motor activity and pose reflexes of male adult rats (Wistar) were observed in the course of high pressure nitrogen compression up to 4,1 MPa. The experiments were carried out under normoxic and hypoxic conditions. Stabile rat motor cortex oxygen tension was recording during the nitrogen compression up to 7,1 MPa under normoxic condition. Sensitivity to nitrogen high pressure to be on the increase under hypoxic conditions. In its turn, resistibility to nitrogen high pressure to be on the decrease under hypoxic conditions (oxygen partial pressure from 0,012 to 0,004 MPa). Quantity of high dencity heat shock proteins (Hsp70) rats motor cortex neurons was 3,44 times higher after course of high pressure nitrogen compression up to 4,1 MPa. For hypoxic exposure (6% O2) the difference was less pronounced - 2,2 times. Data about rat motor cortex neurons Hsp70 concentration under high nitrogen pressure and low oxygen pressure may turn to be a clear base for explanation hypoxic influence on processes of nitrogen narcosis.

  13. Human monocyte heat shock protein 72 responses to acute hypoxic exercise after 3 days of exercise heat acclimation.

    Science.gov (United States)

    Lee, Ben J; Mackenzie, Richard W A; Cox, Valerie; James, Rob S; Thake, Charles D

    2015-01-01

    The aim of this study was to determine whether short-term heat acclimation (STHA) could confer increased cellular tolerance to acute hypoxic exercise in humans as determined via monocyte HSP72 (mHSP72) expression. Sixteen males were separated into two matched groups. The STHA group completed 3 days of exercise heat acclimation; 60 minutes cycling at 50% V̇O2peak in 40°C 20% relative humidity (RH). The control group (CON) completed 3 days of exercise training in 20°C, 40% RH. Each group completed a hypoxic stress test (HST) one week before and 48 hours following the final day of CON or STHA. Percentage changes in HSP72 concentrations were similar between STHA and CON following HST1 (P = 0.97). STHA induced an increase in basal HSP72 (P = 0.03) with no change observed in CON (P = 0.218). Basal mHSP72 remained elevated before HST2 for the STHA group (P 0.05). Percent change in mHSP72 was lower after HST2 in STHA compared to CON (P = 0.02). The mHSP72 response to hypoxic exercise was attenuated following 3 days of heat acclimation. This is indicative of improved tolerance and ability to cope with the hypoxic insult, potentially mediated in part by increased basal reserves of HSP72.

  14. Role of gap junction and connexin-43 in hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Jieying Lin; Niyang Lin

    2006-01-01

    OBJECTEVE:Gap junctin (GJ)is the structural basis for direct intercellular communication of nerve cells . Connexin(Cx) is the protein subunit for constructling GJ channel. Among them, Cx43is closely related with nervous system. Both Cx43 and nervous system play an important role in the pathophysiological development of hypoxic-ischemic injury. We are in attempt to investigate GJ,Cx43 and their correlations with hypoxic-ischemic brain damage by research.DATA SOURCES:Using the terms "brain gap junction"in English and "gap junction"in Chinese, we searched the Medline database and Chinese BioMedical Literature Database as well as China Hospital Knowledge Database to identify the articles published from 1996 to 2006 about GJ and brain hypoxic-ischemic injury.STUDY SELECTION:The articles were selected firstly and abstracts of 250 articles were read thuugh.Articles in which the experimental design met randomized controlled principle were included,and study articles and case reports with repetitve contents were excluded.DATA EXTRACTION:Among 53 included correlative articles, 23 were excluded for repetitive contents and the other 30 were analyzed.DATA SYNTHESIS:GJ,widely esistling in nervous system,plays a key role in maintainling normal differentiation and development as well as physiological function brain tissue.GJ channel is a hydrophilic,low-selectivity and lowohmic channel, which can provide direct channel for intercellular substance transmission and information communication. It plays an important role in the differentiation and development of nerve cells and regulation of physiological function,The funtions of GJ channel are regulated by many factors,which invilved intracellular Ph value, Ca2+concentration, ATP concentration, phosphorylation of Cx, transchannel pressure,some neurohormonal factors,regulatory factors of protein and so on. Cx43 is the main component of GJ channel in the brain tissues. Its expression in the brain tissue of mammal is the strongest

  15. Enhanced non-eupneic breathing following hypoxic, hypercapnic or hypoxic-hypercapnic gas challenges in conscious mice.

    Science.gov (United States)

    Getsy, Paulina M; Davis, Jesse; Coffee, Gregory A; May, Walter J; Palmer, Lisa A; Strohl, Kingman P; Lewis, Stephen J

    2014-12-01

    C57BL6 mice display non-eupneic breathing and spontaneous apneas during wakefulness and sleep as well as markedly disordered breathing following cessation of a hypoxic challenge. We examined whether (1) C57BL6 mice display marked non-eupneic breathing following hypercapnic or hypoxic-hypercapnic challenges, and (2) compared the post-hypoxia changes in non-eupneic breathing of C57BL6 mice to those of B6AF1 (57BL6 dam × A/J sire) and Swiss-Webster mice, which display different ventilatory responses than C57BL6 mice. C57BL6 mice displayed marked increases in respiratory frequency and non-eupneic breathing upon return to room-air after hypoxic (10% O2, 90% N2), hypercapnic (5% CO2, 21% O2 and 74% N2) and hypoxic-hypercapnic (10% O2, 5% CO2 and 85% N2) challenges. B6AF1 mice displayed less tachypnea and reduced non-eupneic breathing post-hypoxia, whereas Swiss-Webster mice displayed robust tachypnea with minimal increases in non-eupneic breathing post-hypoxia. These studies demonstrate that non-eupneic breathing increases after physiologically-relevant hypoxic-hypercapnic challenge in C57BL6 mice and suggest that further studies with these and B6AF1 and Swiss-Webster mice will help define the genetics of non-eupneic breathing.

  16. Extracellular nucleotide derivatives protect cardiomyctes against hypoxic stress

    DEFF Research Database (Denmark)

    Golan, O; Issan, Y; Isak, A

    2011-01-01

    in cardioprotection against hypoxic stress has not been reported. OBJECTIVE: To investigate the role of purine and pyrimidine nucleotides and nucleosides in protective effects in cardiomyocytes subjected to hypoxia. METHODS AND RESULTS: Rat cultured cardiomyocytes were treated with various extracellular nucleotides...... and nucleosides, before or during hypoxic stress. The results revealed that GTP or CTP exhibit cardioprotective ability, as revealed by lactate dehydrogenase (LDH) release, by propidium iodide (PI) staining, by cell morphology, and by preserved mitochondrial activity. Pretreatment with various P2 antagonists...... (suramin, RB-2, or PPADS) did not abolish the cardioprotective effect of the nucleotides. Moreover, P2Y₂ -/- , P2Y₄ -/-, and P2Y₂ -/-/P2Y₄ -/- receptor knockouts mouse cardiomyocytes were significantly protected against hypoxic stress when treated with UTP. These results indicate that the protective effect...

  17. Reference genes for quantitative real-time polymerase chain reaction studies in soybean plants under hypoxic conditions.

    Science.gov (United States)

    Nakayama, T J; Rodrigues, F A; Neumaier, N; Marcelino-Guimarães, F C; Farias, J R B; de Oliveira, M C N; Borém, A; de Oliveira, A C B; Emygdio, B M; Nepomuceno, A L

    2014-02-13

    Quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful tool used to measure gene expression. However, because of its high sensitivity, the method is strongly influenced by the quality and concentration of the template cDNA and by the amplification efficiency. Relative quantification is an effective strategy for correcting random and systematic errors by using the expression level of reference gene(s) to normalize the expression level of the genes of interest. To identify soybean reference genes for use in studies of flooding stress, we compared 5 candidate reference genes (CRGs) with the NormFinder and GeNorm programs to select the best internal control. The expression stability of the CRGs was evaluated in root tissues from soybean plants subjected to hypoxic conditions. Elongation factor 1-beta and actin-11 were identified as the most appropriate genes for RT-qPCR normalization by both the NormFinder and GeNorm analyses. The expression profiles of the genes for alcohol dehydrogenase 1, sucrose synthase 4, and ascorbate peroxidase 2 were analyzed by comparing different normalizing combinations (including no normalization) of the selected reference genes. Here, we have identified potential genes for use as references for RT-qPCR normalization in experiments with soybean roots growing in O2-depleted environments, such as flooding-stressed plants.

  18. Assessment of pain sensitivity in patients with deep bite and sex- and age-matched controls

    DEFF Research Database (Denmark)

    Sonnesen, Ane Liselotte; Svensson, Peter

    2011-01-01

    AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pain...... was scored by the subjects ( n = 60) on a 0 to 10 cm visual analog scale. Subjects drew the perceived pain area on a face and arm chart and described the quality of pain on the McGill Pain Questionnaire. Thresholds for cold detection, cold pain, cold tolerance, warmth detection, heat pain, and heat tolerance...... were assessed on the masseter and brachioradialis muscles. Pressure pain threshold and pain tolerance threshold were determined on the temporomandibular joint, masseter, anterior temporalis, and brachioradialis muscles. The differences between groups, age, and gender were tested by two-way ANOVA...

  19. Quantitative uncertainty and sensitivity analysis of a PWR control rod ejection accident

    Energy Technology Data Exchange (ETDEWEB)

    Pasichnyk, I.; Perin, Y.; Velkov, K. [Gesellschaft flier Anlagen- und Reaktorsicherheit - GRS mbH, Boltzmannstasse 14, 85748 Garching bei Muenchen (Germany)

    2013-07-01

    The paper describes the results of the quantitative Uncertainty and Sensitivity (U/S) Analysis of a Rod Ejection Accident (REA) which is simulated by the coupled system code ATHLET-QUABOX/CUBBOX applying the GRS tool for U/S analysis SUSA/XSUSA. For the present study, a UOX/MOX mixed core loading based on a generic PWR is modeled. A control rod ejection is calculated for two reactor states: Hot Zero Power (HZP) and 30% of nominal power. The worst cases for the rod ejection are determined by steady-state neutronic simulations taking into account the maximum reactivity insertion in the system and the power peaking factor. For the U/S analysis 378 uncertain parameters are identified and quantified (thermal-hydraulic initial and boundary conditions, input parameters and variations of the two-group cross sections). Results for uncertainty and sensitivity analysis are presented for safety important global and local parameters. (authors)

  20. Increasing LIGO sensitivity by feedforward subtraction of auxiliary length control noise

    CERN Document Server

    Meadors, Grant David; Riles, Keith

    2013-01-01

    LIGO, the Laser Interferometer Gravitational-wave Observatory, has been designed and constructed to measure gravitational wave strain via differential arm length. The LIGO 4-km Michelson arms with Fabry-Perot cavities have auxiliary length control servos for suppressing Michelson motion of the beam-splitter and arm cavity input mirrors, which degrades interferometer sensitivity. We demonstrate how a post-facto pipeline called AMPS improves a data sample from LIGO Science Run~6 with feedforward subtraction. Dividing data into 1024-second windows, AMPS numerically fits filter functions representing the frequency-domain transfer functions from Michelson length channels into the gravitational-wave strain data channel for each window, then subtracts the filtered Michelson channel noise (witness) from the strain channel (target). In this paper we describe the algorithm, assess achievable improvements in sensitivity to astrophysical sources, and consider relevance to future interferometry.

  1. MIMO PI Controllers for LTI Systems with Multiple Time Delays Based on ILMIs and Sensitivity Functions

    Directory of Open Access Journals (Sweden)

    Wajdi Belhaj

    2017-01-01

    Full Text Available In this paper, a MIMO PI design procedure is proposed for linear time invariant (LTI systems with multiple time delays. The controller tuning is established in two stages and guarantees performances for set-point changes, disturbance variations, and parametric uncertainties. In the first stage, an iterative linear matrix inequality (ILMI approach is extended to design PI controllers for systems with multiple time delays without performance guarantee, a priori. The second stage is devoted to improve the closed-loop performances by minimizing sensitivity functions. Simulations results carried out on the unstable distillation column, the stable industrial scale polymerization (ISP reactor, and the non-minimum phase 4-tank benchmark prove the efficiency of the proposed approach. A comparative analysis with the conventional internal model control (IMC approach, a multiloop IMC-PI approach, and a previous ILMI PID approach proves the superiority of the proposed approach compared to the related ones.

  2. Microbial mineralization of dichloroethene and vinyl chloride under hypoxic conditions

    Science.gov (United States)

    Bradley, Paul M.; Chapelle, Francis H.

    2011-01-01

    Mineralization of 14C-radiolabled vinyl chloride ([1,2-14C] VC) and cis-dichloroethene ([1,2-14C] cis-DCE) under hypoxic (initial dissolved oxygen (DO) concentrations about 0.1 mg/L) and nominally anoxic (DO minimum detection limit = 0.01 mg/L) was examined in chloroethene-exposed sediments from two groundwater and two surface water sites. The results show significant VC and dichloroethene (DCE) mineralization under hypoxic conditions. All the sample treatments exhibited pseudo-first-order kinetics for DCE and VC mineralization over an extended range of substrate concentrations. First-order rates for VC mineralization were approximately 1 to 2 orders of magnitude higher in hypoxic groundwater sediment treatments and at least three times higher in hypoxic surface water sediment treatments than in the respective anoxic treatments. For VC, oxygen-linked processes accounted for 65 to 85% of mineralization at DO concentrations below 0.1 mg/L, and 14CO2 was the only degradation product observed in VC treatments under hypoxic conditions. Because the lower detection limit for DO concentrations measured in the field is typically 0.1 to 0.5 mg/L, these results indicate that oxygen-linked VC and DCE biodegradation can be significant under field conditions that appear anoxic. Furthermore, because rates of VC mineralization exceeded rates of DCE mineralization under hypoxic conditions, DCE accumulation without concomitant accumulation of VC may not be evidence of a DCE degradative “stall” in chloroethene plumes. Significantly, mineralization of VC above the level that could reasonably be attributed to residual DO contamination was also observed in several nominally anoxic (DO minimum detection limit = 0.01 mg/L) microcosm treatments.

  3. General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression.

    Science.gov (United States)

    Boyer, Nelly; Dallel, Radhouane; Artola, Alain; Monconduit, Lénaïc

    2014-07-01

    Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for

  4. Chemoreflex blunting of hypoxic pulmonary vasoconstriction is vagally mediated.

    Science.gov (United States)

    Wilson, L B; Levitzky, M G

    1989-02-01

    We investigated the role of the autonomic nervous system in the arterial chemoreceptor attenuation of hypoxic pulmonary vasoconstriction (HPV) using anesthetized dogs. Total pulmonary blood flow (Qt) and left pulmonary blood flow (Ql) were determined using electromagnetic flow probes. Carotid body chemoreceptors were perfused using blood pumped from an extracorporeal circuit containing an oxygenator. Four groups were used: 1) prevagotomy (control), 2) bilateral vagotomy, 3) post-atropine, and 4) post-propranolol. Left lung hypoxia decreased Ql/Qt from 42.9 +/- 2.9 to 28.1 +/- 3.0%, from 41.1 +/- 5.3 to 26.7 +/- 4.2%, from 38.6 +/- 1.3 to 22.2 +/- 2.4%, and from 48.2 +/- 4.2 to 28.5 +/- 3.7% in the four groups, respectively. Chemoreceptor stimulation during unilateral hypoxia increased Ql/Qt from 28.1 +/- 3.0 to 39.1 +/- 4.9% and from 28.5 +/- 3.7 to 40.6 +/- 3.7% in the control and propranolol groups. However, chemoreceptor stimulation had no effect on Ql/Qt during left lung hypoxia after vagotomy or atropine, as Ql/Qt went from 26.7 +/- 4.2 to 29.3 +/- 5.2% and from 22.2 +/- 2.4 to 24.1 +/- 1.5% in groups 2 and 3, respectively. Because chemoreceptor stimulation did not affect HPV in groups 2 and 3, we conclude that the chemoreceptor attenuation of HPV is mediated by the parasympathetic nervous system.

  5. Controlled release of protein from biodegradable multi-sensitive injectable poly(ether-urethane) hydrogel.

    Science.gov (United States)

    Li, Xiaomeng; Wang, Yangyun; Chen, Jiaming; Wang, Yinong; Ma, Jianbiao; Wu, Guolin

    2014-03-12

    The synthesis and characterization of multi-sensitive polymers for use as injectable hydrogels for controlled protein/drug delivery is reported. A series of biodegradable multi-sensitive poly(ether-urethane)s were prepared through a simple one-pot condensation of poly(ethylene glycol), 2,2'-dithiodiethanol, N-methyldiethanolamine, and hexamethylene diisocyanate. The sol-gel phase transition behaviors of the obtained copolymers were investigated. Experimental results showed that the aqueous medium comprising the multi-segment copolymers underwent a sol-to-gel phase transition with increasing temperature and pH. At a certain concentration, the copolymer solution could immediately change to a gel under physiological conditions (37 °C and pH 7.4), indicating their suitability as in situ injectable hydrogels in vivo. Insulin was used as a model protein drug for evaluation of the injectable hydrogels as a site-specific drug delivery system. The controlled release of insulin from the hydrogel devices was demonstrated by degradation of the copolymer, which is modulated via the 2,2'-dithiodiethanol content in the poly(ether-urethane)s. These hydrogels having multi-responsive properties may prove to be promising candidates for injectable and controllable protein drug delivery devices.

  6. Control of random Boolean networks via average sensitivity of Boolean functions

    Institute of Scientific and Technical Information of China (English)

    Chen Shi-Jian; Hong Yi-Guang

    2011-01-01

    In this paper, we discuss how to transform the disordered phase into an ordered phase in random Boolean networks. To increase the effectiveness, a control scheme is proposed, which periodically freezes a fraction of the network based on the average sensitivity of Boolean functions of the nodes. Theoretical analysis is carried out to estimate the expected critical value of the fraction, and shows that the critical value is reduced using this scheme compared to that of randomly freezing a fraction of the nodes. Finally, the simulation is given for illustrating the effectiveness of the proposed method.

  7. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC)

    DEFF Research Database (Denmark)

    Dimke, Henrik Anthony

    2011-01-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular...... by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC...

  8. Modeling and sensitivity analysis of consensus algorithm based distributed hierarchical control for dc microgrids

    DEFF Research Database (Denmark)

    Meng, Lexuan; Dragicevic, Tomislav; Vasquez, Juan Carlos

    2015-01-01

    of dynamic study. The aim of this paper is to model the complete DC microgrid system in z-domain and perform sensitivity analysis for the complete system. A generalized modeling method is proposed and the system dynamics under different control parameters, communication topologies and communication speed...... the dynamics of electrical and communication systems interact with each other. Apart from that, the communication characteristics also affect the dynamics of the system. Due to discrete nature of information exchange in communication network, Laplace domain analysis is not accurate enough for this kind...

  9. Cardiomyocyte death induced by ischaemic/hypoxic stress is differentially affected by distinct purinergic P2 receptors.

    Science.gov (United States)

    Cosentino, Simona; Banfi, Cristina; Burbiel, Joachim C; Luo, Haijian; Tremoli, Elena; Abbracchio, Maria P

    2012-05-01

    Blood levels of extracellular nucleotides (e.g. ATP) are greatly increased during heart ischaemia, but, despite the presence of their specific receptors on cardiomyocytes (both P2X and P2Y subtypes), their effects on the subsequent myocardial damage are still unknown. In this study, we aimed at investigating the role of ATP and specific P2 receptors in the appearance of cell injury in a cardiac model of ischaemic/hypoxic stress. Cells were maintained in a modular incubator chamber in a controlled humidified atmosphere of 95% N(2) for 16 hrs in a glucose-free medium. In this condition, we detected an early increase in the release of ATP in the culture medium, which was followed by a massive increase in the release of cytoplasmic histone-associated-DNA-fragments, a marker of apoptosis. Addition of either apyrase, which degrades extracellular ATP, or various inhibitors of ATP release via connexin hemichannels fully abolished ischaemic/hypoxic stress-associated apoptosis. To dissect the role of specific P2 receptor subtypes, we used a combined approach: (i) non-selective and, when available, subtype-selective P2 antagonists, were added to cardiomyocytes before ischaemic/hypoxic stress; (ii) selected P2 receptors genes were silenced via specific small interfering RNAs. Both approaches indicated that the P2Y(2) and P2χ(7) receptor subtypes are directly involved in the induction of cell death during ischaemic/hypoxic stress, whereas the P2Y(4) receptor has a protective effect. Overall, these findings indicate a role for ATP and its receptors in modulating cardiomyocyte damage during ischaemic/hypoxic stress.

  10. Effectiveness of beneficial plant-microbe interactions under hypobaric and hypoxic conditions in an advanced life support system

    Science.gov (United States)

    MacIntyre, Olathe; Stasiak, Michael; Cottenie, Karl; Trevors, Jack; Dixon, Mike

    An assembled microbial community in the hydroponics solution of an advanced life support system may improve plant performance and productivity in three ways: (1) exclusion of plant pathogens from the initial community, (2) resistance to infection, and (3) plant-growth promotion. However, the plant production area is likely to have a hypobaric (low pressure) and hypoxic (low oxygen) atmosphere to reduce structural mass and atmosphere leakage, and these conditions may alter plant-microbe interactions. Plant performance and productivity of radish (Raphanus sativus L. cv. Cherry Bomb II) grown under hypobaric and hypoxic conditions were investigated at the University of Guelph's Controlled Environment Systems Research Facility. Changes in the microbial communities that routinely colonized the re-circulated nutrient solution, roots, and leaves of radishes in these experiments were quantified in terms of similarity in community composition, abundance of bacteria, and community diversity before and after exposure to hypobaric and hypoxic conditions relative to communities maintained at ambient growth conditions. The microbial succession was affected by extreme hypoxia (2 kPa oxygen partial pressure) while hypobaria as low as 10 kPa total pressure had little effect on microbial ecology. There were no correlations found between the physiological profile of these unintentional microbial communities and radish growth. The effects of hypobaric and hypoxic conditions on specific plant-microbe interactions need to be determined before beneficial gnotobiotic communities can be developed for use in space. The bacterial strains Tal 629 of Bradyrhizobium japonicum and WCS417 of Pseudomonas fluorescens, and the plant pathogen Fusarium oxysporum f. sp. raphani will be used in future experiments. B. japonicum Tal 629 promotes radish growth in hydroponics systems and P. fluorescens WCS417 induces systemic resistance to fusarium wilt (F. oxysporum f. sp. raphani) in radish under ambient

  11. Satellite-based empirical models linking river plume dynamics with hypoxic area andvolume

    Science.gov (United States)

    Satellite-based empirical models explaining hypoxic area and volume variation were developed for the seasonally hypoxic (O2 < 2 mg L−1) northern Gulf of Mexico adjacent to the Mississippi River. Annual variations in midsummer hypoxic area and ...

  12. Sensitive biomolecule detection in lateral flow assay with a portable temperature-humidity control device.

    Science.gov (United States)

    Choi, Jane Ru; Hu, Jie; Feng, Shangsheng; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

    2016-05-15

    Lateral flow assays (LFAs) have currently attracted broad interest for point-of-care (POC) diagnostics, but their application has been restricted by poor quantification and limited sensitivity. While the former has been currently solved to some extent by the development of handheld or smartphone-based readers, the latter has not been addressed fully, particularly the potential influences of environmental conditions (e.g., temperature and relative humidity (RH)), which have not yet received serious attention. The present study reports the use of a portable temperature-humidity control device to provide an optimum environmental requirement for sensitivity improvement in LFAs, followed by quantification by using a smartphone. We found that a RH beyond 60% with temperatures of 55-60°C and 37-40°C produced optimum nucleic acid hybridization and antigen-antibody interaction in LFAs, respectively representing a 10-fold and 3-fold signal enhancement over ambient conditions (25°C, 60% RH). We envision that in the future the portable device could be coupled with a fully integrated paper-based sample-to-answer biosensor for sensitive detection of various target analytes in POC settings.

  13. Controlling the Cross-Sensitivity of Carbon Nanotube-Based Gas Sensors to Water Using Zeolites.

    Science.gov (United States)

    Evans, Gwyn P; Buckley, David J; Adedigba, Abdul-Lateef; Sankar, Gopinathan; Skipper, Neal T; Parkin, Ivan P

    2016-10-05

    Carbon nanotube-based gas sensors can be used to detect harmful environmental pollutants such as NO2 at room temperature. Although they show promise as low-powered, sensitive, and affordable monitoring devices, cross-sensitivity of functionalized carbon nanotubes to water vapor often obscures the detection of target molecules. This is a barrier to adoption for monitoring of airborne pollutants because of the varying humidity levels found in real world environments. Zeolites, also known as molecular sieves because of their selective adsorption properties, are used in this work to control the cross-sensitivity of single-walled carbon nanotube (SWCNT)-based sensors to water vapor. Zeolites incorporated into the sensing layer are found to reduce interference effects that would otherwise obscure the identification of NO2 gas, permitting repeatable detection over a range of relative humidities. This significant improvement is found to depend on the arrangement of the SWCNT-zeolite layers in the sensing device, as well as the hydrophilicity of the chosen zeolite.

  14. Long-term existence of cerebral hypoxic tissue in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yidong Wang; Jingrui Pan; Yu Qiu; Xiangpen Li; Mei Li; Ying Peng

    2009-01-01

    BACKGROUND: Hypoxic tissue surrounding the ischemic core may represent the ischemic penumbra following cerebral infarction. However, some studies have shown that the duration of ischemic tissue is longer than previously believed.OBJECTIVE: To clarify whether cerebral hypoxic tissue could survive long-term and whether it is altered in rats following cerebral infarction; to establish an ischemia/reperfusion model in which hypoxic tissue exists for extended periods of time.DESIGN, TIME AND SETTING: A completely randomized grouping and controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University and Medical Research Center, the Second Affiliated Hospital of Sun Yat-sen University between June and December 2008. MATERIALS: 4,9-diaza-3,3,10,10-tetramethyldodecan-2, 11-dione dioxime (BnAO) (HL91), used as the hypoxic marker for autoradiography, was supplied by the Beijing Syncor Star Medicinal, China, and the flesh eluent Na99TcmO4 to mark HL91 was supplied by Guangzhou Medical Isotope Center of the China Institute of Atomic Energy. 2-(2-nitro-1H-imidazole-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) and its antibody ELK3-51, used as a hypoxic marker for immunofluorescence, were supplied by the University of Pennsylvania, USA.METHODS: Male Sprague Dawley rats were randomly divided into four groups: 1.5-hour ischemia/reperfusion group (1.5 h IR), 2-hour ischemia/reperfusion group (2 h IR), 3-hour ischemia/reperfusion group (3 h IR), and permanent ischemia (PI) group, with 21 rats in each group. The middle cerebral artery occlusion model was established using the intraluminal suture method, while reperfusion was performed by removing the suture at each observation time point. However, in the PI group, the suture was left in the artery.MAIN OUTCOME MEASURES: Area and average absorbance of fluorescence, representing hypoxic tissue, were measured by image-analysis.RESULTS: Autoradiography revealed positive hypoxia at days 1 and 14

  15. Does phylogeny control U37K -temperature sensitivity? Implications for lacustrine alkenone paleothermometry

    Science.gov (United States)

    D'Andrea, William J.; Theroux, Susanna; Bradley, Raymond S.; Huang, Xiaohui

    2016-02-01

    Alkenone paleothermometry (via the U37K and U37K‧ indices) has long been used to reconstruct sea surface temperature and has more recently been proven effective in lacustrine settings. Genetic analyses indicate that there is a diversity of different alkenone-producing lacustrine haptophytes, and differences among U37K -temperature calibrations suggest that unique calibrations might be required to quantify past temperature variation from individual lakes. The only term necessary to quantify U37K -inferred temperature relative to a reference period (e.g., modern temperature 20th Century mean) is the slope of the calibration regression, the U37K -temperature sensitivity (i.e., the change in U37K per °C temperature change). Here, we bring together all of the existing U37K -temperature calibrations in order to compare the variability among U37K -temperature sensitivities. We also report a new in situ U37K -temperature calibration along with environmental genomic analysis based on the 18S rRNA gene of an alkenone producing haptophyte from lake Vikvatnet in Norway. We propose and test the hypothesis that U37K -temperature sensitivity is controlled by phylogeny and that this term can be used to quantify past temperature variation from lake sediments if the genetic identity of the lake's alkenone-producer is known. Using the existing calibration data sets, we determine four phylotype-specific U37K -temperature sensitivities for use in cases where in situ calibration is unavailable but the phylogeny of the alkenone producers is known.

  16. Conceptual framework for distributed expert-system use in time-sensitive hierarchical control

    Energy Technology Data Exchange (ETDEWEB)

    Henningsen, J.R.

    1987-01-01

    There are many problems faced by decision makers involved in complex, time-sensitive hierarchical control systems. These may include maintaining knowledge of the functional status of the system components, forecasting the impact of past and future events, transferring information to a distant or poorly connected location, changing the requirements for an operation according to resources available, or creating an independent course of action when system connectivity falls. These problems are transdisciplinary in nature, so decision makers in a variety of organizations face them. This research develops a framework for the use of distributed expert systems in support of time-sensitive hierarchical control systems. Attention is focused on determining ways to enhance the likelihood that a system will remain functional during a crisis in which one or more of the system nodes fail. Options in the use of distributed expert systems for this purpose are developed following investigation of related research in the areas of cooperative and distributed systems. A prototype under development of a generic system model called DES (distributed expert systems) is described. DES is a trimular form of support structure, where a trimule is defined to be a combination of a human decision agent, a component system model and an expert system. This concept is an extension of the domular theory of Tenney and Sandell (1981).

  17. Pain sensitivity and pericranial tenderness in children with tension-type headache: a controlled study

    Science.gov (United States)

    Soee, Ann-Britt L; Skov, Liselotte; Kreiner, Svend; Tornoe, Birte; Thomsen, Lise L

    2013-01-01

    Purpose To compare tenderness and pain sensitivity in children (aged 7–17 years) with tension-type headache (TTH) and healthy controls using total tenderness score (TTS), pressure pain threshold (PPT), and pain perceived at suprapressure pain threshold (supraPPT). Patients and methods Twenty-three children with frequent episodic TTH, 36 with chronic TTH, and 57 healthy controls were included. TTS was measured bilaterally at seven pericranial myofascial structures. PPT and supraPPT were assessed in the finger, m. temporalis, and m. trapezius by a Somedic® algometer. SupraPPT was defined as the pain perceived at a stimulus calculated as the individual site-specific PPT + 50%. Statistics The effect of group, sex, age, headache frequency, intensity, and years on TTS, PPT, and supraPPT was analyzed by general linear models. Confirmatory factor analysis was analyzed for mutual relations between measurements. Results and conclusion Tenderness increased uniformly in both frequent episodic TTH (median 14; interquartile range [IQR] 10–18; P children with frequent episodic TTH and chronic TTH did not show significantly increased sensitivity when measured by PPT or supraPPT. Factor analysis confirmed that the site-specific measurements depended on general latent variables. Consequently, the PPT and supraPPT tests can be assumed to measure central pain-processing levels. PMID:23785242

  18. The short-term effects of diammine silver fluoride on tooth sensitivity: a randomized controlled trial.

    Science.gov (United States)

    Castillo, J L; Rivera, S; Aparicio, T; Lazo, R; Aw, T-C; Mancl, L L; Milgrom, P

    2011-02-01

    Tooth sensitivity is a common clinical problem. This multi-center randomized clinical trial assessed the effectiveness and safety of topical diammine silver fluoride. From two sites (Lima and Cusco, Peru), 126 adults with at least one tooth sensitive to compressed air were randomly assigned to either the experimental treatment or sterile water, and pain was assessed by means of a 100-mm visual analogue scale at 24 hours and 7 days. The diammine silver fluoride reduced pain at 7 days at both sites. At the Lima site, the average change in pain scores between baseline and day 7 for the silver fluoride group was -35.8 (SD = 27.7) mm vs. 0.4 (SD = 16.2) mm for the control group (P < 0.001). In Cusco, the average change in pain scores for the silver fluoride group was -23.4 (SD = 21.0) mm and -5.5 (18.1) mm for the control group (P = 0.002). No tissue ulceration, white changes, or argyria was observed. A small number of participants in the silver fluoride group experienced a mild but transient increase in erythema in the gingiva near the tooth. No changes were observed in the Gingival Index. We concluded that diammine silver fluoride is a clinically effective and safe tooth desensitizer.

  19. Perinatal Hypoxic-Ischemic brain injury; MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Park, Dong Woo; Seo, Chang Hye [Inje University Pusan Paik Hospital, Pusan (Korea, Republic of)

    1994-09-15

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult.

  20. Patterns of neonatal hypoxic-ischaemic brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Linda S. de [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands); Wilhelmina Children' s Hospital, University Medical Centre, Department of Neonatology, KE 04.123.1, P.O. Box 85090, Utrecht (Netherlands); Groenendaal, Floris [University Medical Centre, Department of Neonatology, Wilhelmina Children' s Hospital, Utrecht (Netherlands)

    2010-06-15

    Enormous progress has been made in assessing the neonatal brain, using magnetic resonance imaging (MRI). In this review, we will describe the use of MRI and proton magnetic resonance spectroscopy in detecting different patterns of brain injury in (full-term) human neonates following hypoxic-ischaemic brain injury and indicate the relevance of these findings in predicting neurodevelopmental outcome. (orig.)

  1. Time from uterine incision to delivery and hypoxic neonatal outcomes.

    Science.gov (United States)

    Spain, Janine E; Tuuli, Methodius; Stout, Molly J; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

    2015-04-01

    The objective of this study was to estimate the association between time from uterine incision to delivery and hypoxic neonatal outcomes in nonanomalous term infants. All women undergoing in-labor term cesarean deliveries (CDs) in the first 2 years of an ongoing prospective cohort study were included. The primary exposure was time in seconds from uterine incision to delivery. The primary outcome was a composite of hypoxia-associated neonatal outcomes, defined as at least one of: seizures, hypoxic ischemic encephalopathy, need for hypothermia treatment, and death within 7 days. Of 812 patients who underwent in-labor CD, the composite hypoxia outcome occurred in 18 (2.2%) neonates. There was no significant difference in the rate of hypoxic morbidity with increasing increments of 60 seconds from uterine incision to delivery (p = 0.35). There was a significantly increased risk of hypoxic morbidity in those delivered in the highest quintile (>240 seconds) compared with those in the lowest quintile (≤ 60 seconds) in cesareans performed for an indication other than nonreassuring fetal status (relative risk, 5.58; 95% confidence interval, 1.30-23.91). Overall, duration from uterine incision to delivery for in-labor cesareans of nonanomalous term infants was not associated with an increase in risk of hypoxia-associated morbidities. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

    Directory of Open Access Journals (Sweden)

    Fengbao Luo

    2016-08-01

    Full Text Available Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2, the c-Jun N-terminal kinases (JNK, p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1. Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

  3. Effects of pre- and postnatal protein malnutrition in hypoxic-ischemic rats.

    Science.gov (United States)

    Sanches, Eduardo Farias; Arteni, Nice Sarmento; Spindler, Christiano; Moysés, Felipe; Siqueira, Ionara Rodrigues; Perry, Marcos Luis; Netto, Carlos Alexandre

    2012-02-15

    Neonatal hypoxic-ischemic encephalopathy (HI) is a major cause of nervous system damage and neurological morbidity. Perinatal malnutrition affects morphological, biochemical and behavioral aspects of neural development, including pathophysiological cascades of cell death triggered by ischemic events, so modifying resulting brain damage. Female Wistar rats were subjected to protein restriction during pregnancy and lactation (control group: 25% soybean protein; malnourished group: 7%). Seven days after delivery (PND7), their offspring were submitted to unilateral cerebral HI; rats were then tested for sensorimotor (PND7 and PND60) and memory (PND60) functions. Offspring of malnourished mothers showed marked reduction in body weight starting in lactation and persisting during the entire period of observation. There was a greater sensorimotor deficit after HI in malnourished (M) animals, in righting reflex and in home bedding task, indicating an interaction between diet and hypoxia-ischemia. At PND60, HI rats showed impaired performance when compared to controls in training and test sessions of rota-rod task, however there was no effect of malnutrition per se. In the open field, nourished HI (HI-N) presented an increase in crossings number; this effect was not present in HI-M group. Surprisingly, HI-M rats presented a better performance in inhibitory avoidance task and a smaller hemispheric brain damage as compared to HI-N animals. Our data points to a possible metabolic adaptation in hypoxic-ischemic animals receiving protein malnutrition during pregnancy and lactation; apparently we observed a neuroprotective effect of diet, possibly decreasing the brain energy demand, under a hypoxic-ischemic situation. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects

    Science.gov (United States)

    Chacaroun, Samarmar; Borowik, Anna; Morrison, Shawnda A.; Baillieul, Sébastien; Flore, Patrice; Doutreleau, Stéphane; Verges, Samuel

    2017-01-01

    Objective: Hypoxic exposure can be used as a therapeutic tool by inducing various cardiovascular, neuromuscular, and metabolic adaptations. Hypoxic conditioning strategies have been evaluated in patients with chronic diseases using either sustained (SH) or intermittent (IH) hypoxic sessions. Whether hypoxic conditioning via SH or IH may induce different physiological responses remains to be elucidated. Methods: Fourteen healthy active subjects (7 females, age 25 ± 8 years, body mass index 21.5 ± 2.5 kg·m−2) performed two interventions in a single blind, randomized cross-over design, starting with either 3 x SH (48 h apart), or 3 x IH (48 h apart), separated by a 2 week washout period. SH sessions consisted of breathing a gas mixture with reduced inspiratory oxygen fraction (FiO2), continuously adjusted to reach arterial oxygen saturations (SpO2) of 70–80% for 1 h. IH sessions consisted of 5 min with reduced FiO2 (SpO2 = 70–80%), followed by 3-min normoxia, repeated seven times. During the first (S1) and third (S3) sessions of each hypoxic intervention, cardiorespiratory parameters, and muscle and pre-frontal cortex oxygenation (near infrared spectroscopy) were assessed continuously. Results: Minute ventilation increased significantly during IH sessions (+2 ± 2 L·min−1) while heart rate increased during both SH (+11 ± 4 bpm) and IH (+13 ± 5 bpm) sessions. Arterial blood pressure increased during all hypoxic sessions, although baseline normoxic systolic blood pressure was reduced from S1 to S3 in IH only (−8 ± 11 mmHg). Muscle oxygenation decreased significantly during S3 but not S1, for both hypoxic interventions (S3: SH −6 ± 5%, IH −3 ± 4%); pre-frontal oxygenation decreased in S1 and S3, and to a greater extent in SH vs. IH (−13 ± 3% vs. −6 ± 6%). Heart rate variability indices indicated a significantly larger increase in sympathetic activity in SH vs. IH (lower SDNN, PNN50, and RMSSD values in SH). From S1 to S3, further reduction in

  5. CT and MR in non-neonatal hypoxic-ischemic encephalopathy: radiological findings with pathophysiological correlations

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, Leonardo Guilhermino; Portela, Luiz Antonio Pezzi [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Rovira, Alex [University Hospital Vall d' Hebron, MR Unit, Department of Radiology, Barcelona (Spain); Costa Leite, Claudia da [Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil); Lucato, Leandro Tavares [Hospital Alemao Oswaldo Cruz and Hospital do Coracao, Diagnostic Imaging Division, Sao Paulo (Brazil); Clinics Hospital of the University of Sao Paulo, School of Medicine, Department of Radiology, Sao Paulo (Brazil)

    2010-11-15

    Non-neonatal hypoxic-ischemic encephalopathy is a clinical condition often related to cardiopulmonary arrest that demands critical management and treatment decisions. Management depends mainly on the degree of neurological impairment and prognostic considerations. Computed tomography (CT) is often used to exclude associated or mimicking pathology. If any, only nonspecific signs such as cerebral edema, sulci effacement, and decreased gray matter (GM)/white matter (WM) differentiation are evident. Pseudosubarachnoid hemorrhage, a GM/WM attenuation ratio <1.18, and inverted GM attenuation are associated with a poor prognosis. Magnetic resonance (MR) imaging is more sensitive than CT in assessing brain damage in hypoxic-ischemic encephalopathy. Some MR findings have similarities to those seen pathologically, based on spatial distribution and time scale, such as lesions distributed in watershed regions and selective injury to GM structures. In the acute phase, lesions are better depicted using diffusion-weighted imaging (DWI) because of the presence of cytotoxic edema, which, on T2-weighted images, only become apparent later in the early subacute phase. In the late subacute phase, postanoxic leukoencephalopathy and contrast enhancement could be observed. In the chronic phase, atrophic changes predominate over tissue signal changes. MR can be useful for estimating prognosis when other tests are inconclusive. Some findings, such as the extent of lesions on DWI and presence of a lactate peak and depleted N-acetyl aspartate peak on MR spectroscopy, seem to have prognostic value. (orig.)

  6. A Novel Multiobjective Control of DVR to Enhance Power Quality of Sensitive Load

    Science.gov (United States)

    Pandu, Sathish Babu; Nagappan, Kamaraj

    2015-01-01

    The Dynamic Voltage Restorer (DVR) is one of the fast, flexible, and cost effective solutions available in compensating the voltage-related power quality problems in power distribution systems. In this paper is discussed how power quality enhancement of sensitive load is achieved by applying three versions of Autonomous Group Particle Swarm Optimization like AGPSO1, AGPSO2, and AGPSO3 for tuning the Proportional-Integral DVR controller under balanced and nonlinear load conditions. A novel multiobjective function is formulated to express the control performance of the system, which is quantified using three power quality indices such as Total Harmonic Distortion (THD), voltage sag index, and RMS voltage variation. The obtained results are compared with the Proportional-Integral (PI) controller tuned by Ziegler-Nichols (ZN) method and also by Simple Particle Swarm Optimization based PI controlled DVR. The proposed methodology has improved the performance in terms of the considered power quality indices and the simulation has been carried out in MATLAB/Simulink environment. PMID:26613100

  7. Drought, floods and water quality: Drivers of a severe hypoxic blackwater event in a major river system (the southern Murray-Darling Basin, Australia)

    Science.gov (United States)

    Whitworth, Kerry L.; Baldwin, Darren S.; Kerr, Janice L.

    2012-07-01

    SummaryHypoxic blackwater events are characterised by high levels of dissolved organic carbon in the water column, the metabolism of which depletes dissolved oxygen, which can cause fish and crustacean mortality. Understanding the drivers of and controls on hypoxic blackwater events is important in order to reduce the potential for detrimental water quality impacts from both managed and natural flows. After a decade-long drought in south-eastern Australia, a series of spring and summer flood events in 2010-2011 resulted in a large-scale hypoxic blackwater event in the southern Murray-Darling Basin that affected over 2000 km of river channels and persisted for 6 months. We examined the biogeochemistry and hydrology underpinning this extreme event and found that multiple drivers contributed to the development and persistence of hypoxic blackwater. Inundation of both forested and agricultural floodplains that had not been flooded for over a decade mobilised large stores of reactive carbon. Altered flow seasonality, due to a combination of climatic effects and river regulation, not only increased the risk of hypoxic blackwater generation but also shifted the proportion of bioavailable carbon that was returned to the river channels. Hypolimnetic weir discharge also contributed to hypoxia at some sites. These findings highlight the need for a whole-of-system perspective for the management of regulated river systems - especially in the face of a changing climate.

  8. Threat/reward-sensitivity and hypomanic-personality modulate cognitive-control and attentional neural processes to emotional stimuli.

    Science.gov (United States)

    Pornpattananangkul, Narun; Hu, Xiaoqing; Nusslock, Robin

    2015-11-01

    Temperamental-traits (e.g. threat/reward-sensitivity) are found to modulate cognitive-control and attentional-processes. Yet, it is unclear exactly how these traits interact with emotional-stimuli in the modulation of cognitive-control, as reflected by the N2 event-related potential (ERP), and attentional-processes, as reflected by the P2 and P3 ERPs. Here in an ERP emotional-Go/NoGo task, 36 participants were instructed to inhibit their response to Fearful- and Happy-faces. Individual-differences in threat-sensitivity, reward-sensitivity and hypomanic-personality were assessed through self-report. Hypomanic-personality was assessed, given its relationship with reward-sensitivity and relevance to mood-disorder symptoms. Concerning cognitive-control, individuals with elevated threat-sensitivity displayed more-negative N2s to Happy-NoGo (relative to Fearful-NoGo) faces, whereas both individuals with elevated reward-sensitivity and hypomanic-personality displayed more-negative N2s to Fearful-NoGo (relative to Happy-NoGo) faces. Accordingly, when cognitive-control is required (during Go/NoGo), a mismatch between one's temperament and the valence of the NoGo-stimulus elevates detection of the need for cognitive-control. Conversely, the modulation of attentional-processing was specific to threat-sensitivity, as there was no relationship between either reward-sensitivity or hypomanic-personality and attentional-processing. Elevated threat-sensitivity was associated with enhanced early (P2s) and later (P3s) attentional-processing to Fearful-NoGo (relative to Happy-NoGo) faces. These latter findings support the negative attentional-bias model relating elevated threat-sensitivity with attentional-biases toward negative-stimuli and away from positive-stimuli. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  9. Sustained radiosensitization of hypoxic glioma cells after oxygen pretreatment in an animal model of glioblastoma and in vitro models of tumor hypoxia.

    Science.gov (United States)

    Clarke, Ryon H; Moosa, Shayan; Anzivino, Matthew; Wang, Yi; Floyd, Desiree Hunt; Purow, Benjamin W; Lee, Kevin S

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and lethal form of brain cancer and these tumors are highly resistant to chemo- and radiotherapy. Radioresistance is thought to result from a paucity of molecular oxygen in hypoxic tumor regions, resulting in reduced DNA damage and enhanced cellular defense mechanisms. Efforts to counteract tumor hypoxia during radiotherapy are limited by an attendant increase in the sensitivity of healthy brain tissue to radiation. However, the presence of heightened levels of molecular oxygen during radiotherapy, while conventionally deemed critical for adjuvant oxygen therapy to sensitize hypoxic tumor tissue, might not actually be necessary. We evaluated the concept that pre-treating tumor tissue by transiently elevating tissue oxygenation prior to radiation exposure could increase the efficacy of radiotherapy, even when radiotherapy is administered after the return of tumor tissue oxygen to hypoxic baseline levels. Using nude mice bearing intracranial U87-luciferase xenografts, and in vitro models of tumor hypoxia, the efficacy of oxygen pretreatment for producing radiosensitization was tested. Oxygen-induced radiosensitization of tumor tissue was observed in GBM xenografts, as seen by suppression of tumor growth and increased survival. Additionally, rodent and human glioma cells, and human glioma stem cells, exhibited prolonged enhanced vulnerability to radiation after oxygen pretreatment in vitro, even when radiation was delivered under hypoxic conditions. Over-expression of HIF-1α reduced this radiosensitization, indicating that this effect is mediated, in part, via a change in HIF-1-dependent mechanisms. Importantly, an identical duration of transient hyperoxic exposure does not sensitize normal human astrocytes to radiation in vitro. Taken together, these results indicate that briefly pre-treating tumors with elevated levels of oxygen prior to radiotherapy may represent a means for selectively targeting radiation

  10. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha.

    Science.gov (United States)

    Rius, Jordi; Guma, Monica; Schachtrup, Christian; Akassoglou, Katerina; Zinkernagel, Annelies S; Nizet, Victor; Johnson, Randall S; Haddad, Gabriel G; Karin, Michael

    2008-06-05

    The hypoxic response is an ancient stress response triggered by low ambient oxygen (O2) (ref. 1) and controlled by hypoxia-inducible transcription factor-1 (HIF-1), whose alpha subunit is rapidly degraded under normoxia but stabilized when O2-dependent prolyl hydroxylases (PHDs) that target its O2-dependent degradation domain are inhibited. Thus, the amount of HIF-1alpha, which controls genes involved in energy metabolism and angiogenesis, is regulated post-translationally. Another ancient stress response is the innate immune response, regulated by several transcription factors, among which NF-kappaB plays a central role. NF-kappaB activation is controlled by IkappaB kinases (IKK), mainly IKK-beta, needed for phosphorylation-induced degradation of IkappaB inhibitors in response to infection and inflammation. IKK-beta is modestly activated in hypoxic cell cultures when PHDs that attenuate its activation are inhibited. However, defining the relationship between NF-kappaB and HIF-1alpha has proven elusive. Using in vitro systems, it was reported that HIF-1alpha activates NF-kappaB, that NF-kappaB controls HIF-1alpha transcription and that HIF-1alpha activation may be concurrent with inhibition of NF-kappaB. Here we show, with the use of mice lacking IKK-beta in different cell types, that NF-kappaB is a critical transcriptional activator of HIF-1alpha and that basal NF-kappaB activity is required for HIF-1alpha protein accumulation under hypoxia in cultured cells and in the liver and brain of hypoxic animals. IKK-beta deficiency results in defective induction of HIF-1alpha target genes including vascular endothelial growth factor. IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation.

  11. Pain sensitivity and pericranial tenderness in children with tension-type headache: a controlled study

    Directory of Open Access Journals (Sweden)

    Soee ABL

    2013-06-01

    Full Text Available Ann-Britt L Soee,1 Liselotte Skov,1 Svend Kreiner,4 Birte Tornoe,1,2 Lise L Thomsen3 1Department of Paediatrics, Children's Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 3Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen Denmark; 4Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark Purpose: To compare tenderness and pain sensitivity in children (aged 7–17 years with tension-type headache (TTH and healthy controls using total tenderness score (TTS, pressure pain threshold (PPT, and pain perceived at suprapressure pain threshold (supraPPT. Patients and methods: Twenty-three children with frequent episodic TTH, 36 with chronic TTH, and 57 healthy controls were included. TTS was measured bilaterally at seven pericranial myofascial structures. PPT and supraPPT were assessed in the finger, m. temporalis, and m. trapezius by a Somedic® algometer. SupraPPT was defined as the pain perceived at a stimulus calculated as the individual site-specific PPT + 50%. Statistics: The effect of group, sex, age, headache frequency, intensity, and years on TTS, PPT, and supraPPT was analyzed by general linear models. Confirmatory factor analysis was analyzed for mutual relations between measurements. Results and conclusion: Tenderness increased uniformly in both frequent episodic TTH (median 14; interquartile range [IQR] 10–18; P < 0.001 and chronic TTH (median 13; IQR 9–20; P < 0.001 compared to controls (median 5, IQR 3–11. However, the children with frequent episodic TTH and chronic TTH did not show significantly increased sensitivity when measured by PPT or supraPPT. Factor analysis confirmed that the site-specific measurements depended on general latent variables. Consequently, the PPT and supraPPT tests can be assumed to measure

  12. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1.

    Science.gov (United States)

    Brown, Louisa M; Cowen, Rachel L; Debray, Camille; Eustace, Amanda; Erler, Janine T; Sheppard, Freda C D; Parker, Catriona A; Stratford, Ian J; Williams, Kaye J

    2006-02-01

    The resistance of hypoxic cells to conventional chemotherapy is well documented. Using both adenovirus-mediated gene delivery and small molecules targeting hypoxia-inducible factor-1 (HIF-1), we evaluated the impact of HIF-1 inhibition on the sensitivity of hypoxic tumor cells to etoposide. The genetic therapy exploited a truncated HIF-1alpha protein that acts as a dominant-negative HIF-1alpha (HIF-1alpha-no-TAD). Its functionality was validated in six human tumor cell lines using HIF-1 reporter assays. An EGFP-fused protein demonstrated that the dominant-negative HIF-1alpha was nucleus-localized and constitutively expressed irrespective of oxygen tension. The small molecules studied were quinocarmycin monocitrate (KW2152), its analog 7-cyanoquinocarcinol (DX-52-1), and topotecan. DX-52-1 and topotecan have been previously established as HIF-1 inhibitors. HT1080 and HCT116 cells were treated with either AdHIF-1alpha-no-TAD or nontoxic concentrations (0.1 microM; TAD (multiplicity of infection 50) ablated the anoxic resistance in both cell lines (IC(50) values: HT1080, 0.7 +/- 0.04 microM; HCT116, 3 +/- 1 microM). HIF-1alpha-no-TAD expression inhibited HIF-1-mediated down-regulation of the proapoptotic protein Bid under anoxia. These data support the potential development of HIF-1 targeted approaches in combination with chemotherapy, where hypoxic cell resistance contributes to treatment failure.

  13. Neuroprotective effects of volume-regulated anion channel blocker DCPIB on neonatal hypoxic-ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Ammar ALIBRAHIM; Li-yan ZHAO; Christine You-jin BAE; Andrew BARSZCZYK; Christopher LF SUN; Guan-lei WANG; Hong-shuo SUN

    2013-01-01

    Aim:To evaluate the role of swelling-induced activation of volume-regulated anion channels (VRACs) in a neonatal hypoxic-ischemic injury model using the selective VRAC blocker 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on5-yl) oxobutyric acid (DCPIB).Methods:Cerebral hypoxic-ischemic injury was induced in 7-day-old mouse pups with Rice-Vannucci method.Prior to the onset of ischemia,the animals were ip administered DCPIB (10 mg/kg).The animals were sacrificed 24 h afterwards,coronal sections of the brains were cut and the areas of infarct were examined using TTC staining and an image-analysis system.Cultured PC12 cells were subjected to oxygen-glucose deprivation (OGD) for 4 h.The cellular viability was assessed using Cell Counting Kit 8.Intracellular chloride concentration [Clˉ]i was measured using 6-methoxy-N-ethylquinolinium iodide.Results:DCPIB-treated mice showed a significant reduction in hemispheric corrected infarct volume (26.65%+2.23%) compared to that in vehicle-treated mice (45.52%+1.45%,P<O.O01).DCPIB-treated mice also showed better functional recovery as they were more active than vehicle-treated mice at 4 and 24 h post injury.In cultured PC12 cells,DCPIB (10 μmol/L) significantly reduced OGD-induced cell death.Moreover,DCPIB (20 μmol/L) blocked hypotonic-induced decrease in [Clˉ]i in PC12 cells of both control and OGD groups.Conclusion:The results further support the pathophysiological role of VRACs in ischemic brain injury,and suggest DCPIB as a potential,easily administrable agent targeting VRACs in the context of perinatal and neonatal hypoxic-ischemic brain injury.

  14. The Effect of Ginkgo Biloba Extract on Hypoxic Fraction of C3H Mouse Fibrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Chul Koo; Yi, Chun Ja; Ha, Sung Whan; Park, Charn Il [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-09-15

    Purpose : To investigate the effect of Ginkgo biloba extract (GBE) on hypoxic cell fraction and metabolic status in fibrosarcoma (FSa II) of C3H mouse. Materials and Methods : Fibrosarcoma (Fsa II), 6mm in diameter, growing in the right hind leg muscle of C3H mouse was used for estimation of hypoxic cell fraction using comparison of TCD{sub 50}. Radiation was given one hour after administration of GBE (100 mg/Kg, i.p.) with or without priming dose of GBE (100 mg/Kg, i.p.) given 24 hours earlier. Radiation was also given under air breathing condition or clamp hypoxia without GBE as controls. {sup 31}P NMR spectroscopy was performed before and one hour after administration of GBE with or without priming dose of GBE. Results : TCD{sub 50/120's} were 81.7(77.7-86.0) Gy when irradiated under clamped hypoxia, 69.6 (66.8-72.5) Gy under air breathing condition,67.5(64.1-71.1) Gy with a single dose of GBE (100 mg/kg) given one hour before irradiation, and 62.2(59.1-65.5) Gy with two doses of GBE given at 25 hours and one hour before irradiation. The hypoxic cell fractions, estimated from TCD50/120's were 1.6% under air breathing condition, 7.2% after single dose of GBE, and 2.7% after two doses of GBE. Metabolic status of tumor, probably by increasing the blood flow and delivery of oxygen and nutrients, resulting in increased radiosensitivity of tumor.

  15. Field study of cyclic hypoxic effects on gene expression in grass shrimp hepatopancreas.

    Science.gov (United States)

    Li, Tiandao; Brouwer, Marius

    2013-12-01

    Grass shrimp, Palaemonetes pugio, are widely used for ecological and toxicological research. They commonly experience cyclic hypoxia in their natural habitats. The response of grass shrimp to laboratory-controlled cyclic hypoxia has been studied in detail, but little is known about how field acclimatized grass shrimp regulate the gene expression and response to cyclic hypoxia. In this study we examined morphometric parameters, relative fecundity and gene expression of grass shrimp collected from two areas in Weeks Bay (Mobile, Alabama). One is a traditionally normoxic location (WBM), and the other is a traditionally cyclic hypoxic location (WC). In the week preceding grass shrimp collection dissolved oxygen (DO) at the field sites was measured continuously. DO was shrimp were significantly greater than weight and length of WC shrimp. WBM shrimp had more eggs than WC shrimp, but the difference was not significant. Shrimp from WC had a significant higher number of parasites than those from WBM. A cDNA microarray was utilized to investigate the changes in gene expression in grass shrimp hepatopancreas. Five genes, previously identified as hypoxia/cyclic hypoxia-responsive genes in laboratory exposure studies, were significantly up-regulated in WC shrimp relative to WBM. A total of 5 genes were significantly down-regulated in the field study. Only one of those genes, vitellogenin, has been previously found in chronic and cyclic hypoxic studies. Up and down-regulation of 7 selected genes was confirmed by qPCR. The overall pattern of gene expression in wild shrimp from cyclic DO sites in Weeks Bay showed only weak correlations with gene expression in shrimp from chronic and cyclic hypoxic laboratory studies. It appears therefore that transcriptome profiles of laboratory acclimated animals are of limited utility for understanding responses in field acclimatized animals that are exposed to a broader array of environmental variables.

  16. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    Science.gov (United States)

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  17. Robust Stability Clearance of Flight Control Law Based on Global Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Liuli Ou

    2014-01-01

    Full Text Available To validate the robust stability of the flight control system of hypersonic flight vehicle, which suffers from a large number of parametrical uncertainties, a new clearance framework based on structural singular value (μ theory and global uncertainty sensitivity analysis (SA is proposed. In this framework, SA serves as the preprocess of uncertain model to be analysed to help engineers to determine which uncertainties affect the stability of the closed loop system more slightly. By ignoring these unimportant uncertainties, the calculation of μ can be simplified. Instead of analysing the effect of uncertainties on μ which involves solving optimal problems repeatedly, a simpler stability analysis function which represents the effect of uncertainties on closed loop poles is proposed. Based on this stability analysis function, Sobol’s method, the most widely used global SA method, is extended and applied to the new clearance framework due to its suitability for system with strong nonlinearity and input factors varying in large interval, as well as input factors subjecting to random distributions. In this method, the sensitive indices can be estimated via Monte Carlo simulation conveniently. An example is given to illustrate the efficiency of the proposed method.

  18. Hypoxic radiosensitization by the antimicrobial methyl paraben

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P.; Sade, N.

    1984-08-01

    The antimicrobial preservative, methyl paraben (methyl-4-hydroxybenzoate) sensitizes anoxic buffered suspensions of Staphylococcus aureus to gamma-radiation. The maximal response at an 0.5 mM concentration represents a 150 percent increase in response over that for deoxygenated suspensions without additive, and 80 percent of the response for aerated suspensions alone. Methyl paraben is not toxic to the test organism under the present test conditions.

  19. Switch probability context (in)sensitivity within the cognitive control network.

    Science.gov (United States)

    De Baene, Wouter; Brass, Marcel

    2013-08-15

    Cognitive control processes refer to the ability to flexibly adapt one's thoughts and actions in the pursuit of an internal goal. Task preparation is a central aspect of cognitive control and has generally been studied using explicitly cued task-switching paradigms. Over the last decade, numerous fMRI studies have identified a fronto-parietal network to exhibit greater activity during the preparation of task switches than during the preparation of task repetitions, which is assumed to reflect endogenous cognitive control processes. There is, however, a huge variability in preparatory switch-specific brain activity reported in the imaging literature on task-switching. One factor that might explain this heterogeneity is the difference in switch probability across studies. In the current fMRI study, we examined which preparation-related cognitive control areas are susceptible to such contextual differences by manipulating the switch probability within subjects. In the low switch probability (30% switch trials) blocks, we found the frequently observed switch-related preparatory activation in fronto-parietal areas. In the high switch probability (50% switch trials) blocks, however, only part of these areas (more particularly the (pre-) SMA, extending into the dorsal ACC and the superior parietal lobule) showed higher activation in switch compared to repeat trials. The activation levels in the other areas (the lateral prefrontal cortex, inferior parietal lobule and middle temporal gyrus) were very similar for switch and repeat trials. Our results suggest a functional dissociation within the cognitive control network with some brain areas being sensitive to the switch probability context while others are not.

  20. Stability and sensitivity analysis of experimental data for passive control of a turbulent wake

    Science.gov (United States)

    Siconolfi, Lorenzo; Camarri, Simone; Trip, Renzo; Fransson, Jens H. M.

    2016-11-01

    When the linear stability analysis is applied to the mean flow field past a bluff body, a quasi-marginally stable mode is identified, with a frequency very close to the real vortex shedding one. A formally consistent approach to justify this kind of analysis is based on a triple decomposition of the flow variables. With this formalism, the adjoint-based sensitivity analysis can be extended to investigate passive controls of high-Reynolds-number wakes (e.g.). The objective of the present work is to predict the effect of a small control cylinder on the vortex shedding frequency in a turbulent wake with an analysis which solely relies on PIV measurements available for the considered flow. The key ingredient of the numerical analysis is an ad-hoc tuned model for the mean flow field, built using an original procedure which includes all the experimental information available on the flow. This analysis is here applied to the wake flow past a thick porous plate at Reynolds numbers in the range between Re = 6 . 7 ×103 and Re= 5 . 3 ×104 . It is shown that the derived control map agrees reasonably well with the equivalent map obtained experimentally.

  1. Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus

    2017-01-01

    To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis...... min after being exposed to and 4 hours after the exposure. Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons...

  2. Magnetic field effects in dye-sensitized solar cells controlled by different cell architecture

    Science.gov (United States)

    Klein, M.; Pankiewicz, R.; Zalas, M.; Stampor, W.

    2016-07-01

    The charge recombination and exciton dissociation are generally recognized as the basic electronic processes limiting the efficiency of photovoltaic devices. In this work, we propose a detailed mechanism of photocurrent generation in dye-sensitized solar cells (DSSCs) examined by magnetic field effect (MFE) technique. Here we demonstrate that the magnitude of the MFE on photocurrent in DSSCs can be controlled by the radius and spin coherence time of electron-hole (e-h) pairs which are experimentally modified by the photoanode morphology (TiO2 nanoparticles or nanotubes) and the electronic orbital structure of various dye molecules (ruthenium N719, dinuclear ruthenium B1 and fully organic squaraine SQ2 dyes). The observed MFE is attributed to magnetic-field-induced spin-mixing of (e-h) pairs according to the Δg mechanism.

  3. Thiopental inhibits global protein synthesis by repression of eukaryotic elongation factor 2 and protects from hypoxic neuronal cell death.

    Directory of Open Access Journals (Sweden)

    Christian I Schwer

    Full Text Available Ischemic and traumatic brain injury is associated with increased risk for death and disability. The inhibition of penumbral tissue damage has been recognized as a target for therapeutic intervention, because cellular injury evolves progressively upon ATP-depletion and loss of ion homeostasis. In patients, thiopental is used to treat refractory intracranial hypertension by reducing intracranial pressure and cerebral metabolic demands; however, therapeutic benefits of thiopental-treatment are controversially discussed. In the present study we identified fundamental neuroprotective molecular mechanisms mediated by thiopental. Here we show that thiopental inhibits global protein synthesis, which preserves the intracellular energy metabolite content in oxygen-deprived human neuronal SK-N-SH cells or primary mouse cortical neurons and thus ameliorates hypoxic cell damage. Sensitivity to hypoxic damage was restored by pharmacologic repression of eukaryotic elongation factor 2 kinase. Translational inhibition was mediated by calcium influx, activation of the AMP-activated protein kinase, and inhibitory phosphorylation of eukaryotic elongation factor 2. Our results explain the reduction of cerebral metabolic demands during thiopental treatment. Cycloheximide also protected neurons from hypoxic cell death, indicating that translational inhibitors may generally reduce secondary brain injury. In conclusion our study demonstrates that therapeutic inhibition of global protein synthesis protects neurons from hypoxic damage by preserving energy balance in oxygen-deprived cells. Molecular evidence for thiopental-mediated neuroprotection favours a positive clinical evaluation of barbiturate treatment. The chemical structure of thiopental could represent a pharmacologically relevant scaffold for the development of new organ-protective compounds to ameliorate tissue damage when oxygen availability is limited.

  4. Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

    Directory of Open Access Journals (Sweden)

    Heikal L

    2016-08-01

    Full Text Available Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1 1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK Abstract: The cytoprotective effects of erythropoietin (EPO and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP, were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2 and hypoxic (1% O2 conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay, we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS; the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis. Keywords

  5. [Mechanism of protective effects of tumor necrosis factor receptor associated protein 1 on hypoxic cardiomyocytes of rats].

    Science.gov (United States)

    Xiang, F; Zhang, D X; Ma, S Y; Huang, Y S

    2016-12-20

    Objective: To investigate the mechanism of protective effects of tumor necrosis factor receptor associated protein 1 (TRAP1) on hypoxic cardiomyocytes of rats. Methods: Primary cultured cardiomyocytes were obtained from neonatal Sprague-Dawley rats (aged 1 to 3 days) and then used in the following experiments. (1) Cells were divided into group TRAP1 and control group according to the random number table (the same grouping method below), and then the total protein of cells was extracted. Total protein of cells in group TRAP1 was added with mouse anti-rat TRAP1 monoclonal antibody, while that in control group was added with the same type of IgG from mouse. Co-immunoprecipitation and protein mass spectrography analysis were used to determine the possible proteins interacted with TRAP1. (2) Cells were divided into normoxia blank control group (NBC), normoxia+ TRAP1 interference control group (NTIC), normoxia+ TRAP1 interference group (NTI), normoxia+ TRAP1 over-expression control group (NTOC), and normoxia+ TRAP1 over-expression group (NTO), with 1 well in each group. Cells in group NBC were routinely cultured, while cells in the latter four groups were respectively added with TRAP1 RNA interference empty virus vector, TRAP1 RNA interference adenovirus vector, TRAP1 over-expression empty virus vector, and TRAP1 over-expression adenovirus vector. Another batch of cells were divided into group NBC, hypoxic blank control group (HBC), hypoxic+ TRAP1 interference control group (HTIC), hypoxic+ TRAP1 interference group (HTI), hypoxic+ TRAP1 over-expression control group (HTOC), and hypoxic+ TRAP1 over-expression group (HTO), with 1 well in each group. Cells in hypoxic groups were under hypoxic condition for 6 hours after being treated as those in the corresponding normoxia groups, respectively. The mRNA expression of cytochrome c oxidase subunit Ⅱ (COXⅡ) of cells in each group was detected by real time fluorescent quantitive reverse transcription polymerase chain

  6. Differentiation between peritrigonal terminal zones and hypoxic-ischemic white matter injury on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Liauw, Lishya [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: l.liauw@rad.umcn.nl; Grond, Jeroen van der [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: j.van_der_grond@lumc.nl; Slooff, Valerie [Emma Children' s Hospital AMC, University of Amsterdam, P.O. Box 22700, 1100 DD Amsterdam (Netherlands)], E-mail: v.d.slooff@amc.uva.nl; Wiggers-de Bruine, Francisca [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: f.t.wiggers-de_bruine@lumc.nl; Laan, Laura [Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: l.a.e.m.laan@lumc.nl; Cessie, Saskia le [Department of Medical Statistics and Bio-Informatics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden (Netherlands)], E-mail: c.le_cessie@lumc.nl; Buchem, Mark van [Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: m.a.van_buchem@lumc.nl; Wezel-Meijler, Gerda van [Department of Neonatology, J6S-201, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden (Netherlands)], E-mail: g.van_wezel-meijler@lumc.nl

    2008-03-15

    The differentiation between terminal zones and pathological signal intensity changes on MRI of children and young adults is of diagnostic importance. We assessed the diagnostic value of several morphological features on MRI to differentiate between terminal zones and hypoxic-ischemic white matter injury. We selected all brain MRI examinations performed in subjects up to 20 years of age showing increased signal intensity on T2-weighted images in the peritrigonal areas. 75 individuals were assigned to a patient group (n = 28) if there was evidence of hypoxia-ischemia during the perinatal period or a control group (n = 47). Aspect, location, extent, shape, and borders of signal intensity changes in the peritrigonal areas were studied. Signal intensity of the peritrigonal areas was related to signal intensity of surrounding white matter. Presence of Virchow Robin spaces, hypoxic-ischemic abnormalities, and local atrophy were also recorded. Chi-squared tests assessed whether presence or absence of morphological characteristics differed between patients and controls. Logistic regression analysis studied which characteristics were best to discriminate between the two groups. Very high signal intensity of the peritrigonal areas on FLAIR (Odds Ratio 25) and presence of local atrophy (Odds Ratio 14.3) were best predictors to discriminate between the two groups.

  7. Cable bacteria generate a firewall against euxinia in seasonally hypoxic basins.

    Science.gov (United States)

    Seitaj, Dorina; Schauer, Regina; Sulu-Gambari, Fatimah; Hidalgo-Martinez, Silvia; Malkin, Sairah Y; Burdorf, Laurine D W; Slomp, Caroline P; Meysman, Filip J R

    2015-10-27

    Seasonal oxygen depletion (hypoxia) in coastal bottom waters can lead to the release and persistence of free sulfide (euxinia), which is highly detrimental to marine life. Although coastal hypoxia is relatively common, reports of euxinia are less frequent, which suggests that certain environmental controls can delay the onset of euxinia. However, these controls and their prevalence are poorly understood. Here we present field observations from a seasonally hypoxic marine basin (Grevelingen, The Netherlands), which suggest that the activity of cable bacteria, a recently discovered group of sulfur-oxidizing microorganisms inducing long-distance electron transport, can delay the onset of euxinia in coastal waters. Our results reveal a remarkable seasonal succession of sulfur cycling pathways, which was observed over multiple years. Cable bacteria dominate the sediment geochemistry in winter, whereas, after the summer hypoxia, Beggiatoaceae mats colonize the sediment. The specific electrogenic metabolism of cable bacteria generates a large buffer of sedimentary iron oxides before the onset of summer hypoxia, which captures free sulfide in the surface sediment, thus likely preventing the development of bottom water euxinia. As cable bacteria are present in many seasonally hypoxic systems, this euxinia-preventing firewall mechanism could be widely active, and may explain why euxinia is relatively infrequently observed in the coastal ocean.

  8. Co-expression of DevR and DevR(N-Aph proteins is associated with hypoxic adaptation defect and virulence attenuation of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Shyamasree De Majumdar

    Full Text Available BACKGROUND: The DevR response regulator is implicated in both hypoxic adaptation and virulence of Mycobacterium tuberculosis (M. tb. DevR regulon genes are powerfully induced in vivo implicating them in bacterial adaptation to host control strategies. A better understanding of DevR function will illumine the way for new strategies to control and treat tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Towards this objective, we used a combination of genetic, microbiological, biochemical, cell biological tools and a guinea pig virulence assay to compare the hypoxic adaptation and virulence properties of two novel M. tb strains, namely, a devR disruption mutant, Mut1, that expresses C-terminal truncated N-terminal domain of DevR (DevR(NTD as a fusion protein with AphI (DevR(N-Kan, and its complemented strain, Comp1, that expresses intact DevR along with DevR(N-Kan. Comp1 bacteria exhibit a defect in DevR-mediated phosphosignalling, hypoxic induction of HspX and also hypoxic survival. In addition, we find that Comp1 is attenuated in virulence in guinea pigs and shows decreased infectivity of THP-1 cells. While Mut1 bacilli are also defective in hypoxic adaptation and early growth in spleen, they exhibit an overall virulence comparable to that of wild-type bacteria. CONCLUSIONS/SIGNIFICANCE: The hypoxic defect of Comp1 is associated to a defect in DevR expression level. The demonstrated repression of DevR function by DevR(N-Kan suggests that such a knockdown approach could be useful for evaluating the activity of DevRS and other two-component signaling pathways. Further investigation is necessary to elucidate the mechanism underlying Comp1 attenuation.

  9. Cheyne-Stokes respiration: hypoxia plus a deep breath that interrupts hypoxic drive, initiating cyclic breathing.

    Science.gov (United States)

    Guntheroth, Warren G

    2011-11-01

    In the 19th Century, Cheyne and Stokes independently reported cycles of respiration in patients with heart failure, beginning with apnea, followed by a few breaths. However Cheyne-Stokes respiration (C-SR) can also occur in healthy individuals with sleep, and was demonstrated in 1908 with voluntary hyperventilation, followed by apnea that Haldane blamed on hypoxia, subsequently called post-hyperventilation apnea. Additional theories explaining C-SR did not appear until 1954, based on control theory, specifically a feed-back regulator controlling CO(2). This certainly describes control of normal respiration, but to produce an unstable state such as C-SR requires either a very long transit time (3½ min) or an increase of the controller gain (13 times), physiologically improbable. There is general agreement that apnea initiates C-SR but that has not been well explained except for post-hyperventilation apnea, and that explanation is not compatible with a study by Nielsen and Smith in 1951. They plotted the effects of diminished oxygen on ventilation (V) in relation to CO(2) (Fig. 1). They found that the slope of V/CO(2) (gain) increased with hypoxia, but it flattened at a moderate CO(2) level and had nointercept with zero (apnea). It is also incompatible with our published findings in 1975 that showed that apnea did not occur until an extreme level of hypoxia occurred (the PO(2) fell below 10 mmHg), followed shortly by gasping. Much milder hypoxia underlies most cases of C-SR, when hypoxic drive replaces the normal CO(2)-based respiratory drive, in a failsafe role. I hypothesize that the cause of apnea is a brief interruption of hypoxic drive caused by a pulse of oxygen from a stronger than average breath, such as a sigh. The rapidity of onset of apnea in response to a pulse of oxygen, reflects the large pressure gradient for oxygen from air to lung with each breath, in contrast to CO(2). With apnea, there is a gradual fall in oxygen, resulting in a resumption of

  10. Increased alphaCGRP potency and CGRP-receptor antagonist affinity in isolated hypoxic porcine intramyocardial arteries

    DEFF Research Database (Denmark)

    Hasbak, Philip; Eskesen, Karen; Schifter, Søren

    2005-01-01

    receptor mRNA. 6. We conclude that hypoxic incubation increases the relaxation and cAMP production induced by alphaCGRP and AMY in rings of porcine coronary arteries in vitro. A concomitant release of adenosine, a cyclooxygenase product, an endothelium-derived substance, activation of vascular ATP...... effect in hypoxia. The Schild plot-derived pK(B) values revealed an increase in the apparent affinity of the antagonist for the CGRP(1) receptor from 7.0 to 7.2 under control conditions versus 8.0 in hypoxia. 5. Removal of endothelium, peptidase inhibitors, preincubation with the adenosine A(2A) receptor......1. This study describes the effects of hypoxia on relaxing responses and cAMP production induced by the known vasodilator peptides: alphaCGRP, amylin (AMY) and adrenomedullin (AM) on isolated pig coronary arteries in vitro. 2. Hypoxic incubation increased the vasorelaxant effect of alphaCGRP (four...

  11. An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response.

    Science.gov (United States)

    Calzado, Marco A; de la Vega, Laureano; Möller, Andreas; Bowtell, David D L; Schmitz, M Lienhard

    2009-01-01

    Oxygen deprivation (hypoxia) results in reprogrammed gene expression patterns that induce multifaceted cellular responses. Here we identify a regulated interaction between the serine/threonine kinase HIPK2 and the ubiquitin E3 ligase Siah2 as a mechanism controlling the hypoxic response. Under normoxic conditions, several mechanisms ensure HIPK2 stability: only a fraction of HIPK2 is found in association with Siah2, whereas HIPK2-mediated phosphorylation of this E3 ligase at positions 26, 28 and 68 weakens mutual binding and destabilizes its phosphorylated interaction partner. Hypoxic conditions allow a markedly increased HIPK2/Siah2 interaction and result in efficient polyubiquitylation and proteasomal degradation of the kinase. Accordingly, hypoxia-induced HIPK2 elimination is markedly reduced in Siah2-deficient cells. As HIPK2 has an important role as a negative regulator of gene expression, its elimination from promoter-associated repressor complexes allows the induction of a substantial fraction of hypoxia-induced genes.

  12. Development of virtual bait stations to control Argentine ants (Hymenoptera: Formicidae) in environmentally sensitive habitats.

    Science.gov (United States)

    Choe, Dong-Hwan; Vetter, Richard S; Rust, Michael K

    2010-10-01

    A novel bait station referred to as a virtual bait station was developed and tested against field populations of the invasive Argentine ant, Linepithema humile (Mayr) (Hymenoptera: Formicidae), at White Beach, Camp Pendleton, in Oceanside, CA. White Beach is a nesting habitat for an endangered seabird, the California least tern (Sterna antillarum browni Mearns). The beach is heavily infested with Argentine ants, one of the threats for the California least tern chicks. Conventional pest control strategies are prohibited because of the existence of the protected bird species and the site's proximity to the ocean. The bait station consisted of a polyvinyl chloride pipe that was treated on the inside with fipronil insecticide at low concentrations to obtain delayed toxicity against ants. The pipe was provisioned with an inverted bottle of 25% sucrose solution, then capped, and buried in the sand. Foraging ants crossed the treated surface to consume the sucrose solution. The delayed toxicity of fipronil deposits allowed the ants to continue foraging on the sucrose solution and to interact with their nestmates, killing them within 3-5 d after exposure. Further modification of the bait station design minimized the accumulation of dead ants in the sucrose solution, significantly improving the longevity and efficacy of the bait station. The virtual bait station exploits the foraging behavior of the ants and provides a low impact approach to control ants in environmentally sensitive habitats. It excluded all insects except ants, required only milligram quantities of toxicant, and eliminated the problem of formulating toxicants into aqueous sugar baits.

  13. Children with ADHD Show No Deficits in Plantar Foot Sensitivity and Static Balance Compared to Healthy Controls

    Science.gov (United States)

    Schlee, Gunther; Neubert, Tom; Worenz, Andreas; Milani, Thomas L.

    2012-01-01

    The goal of this study was to investigate plantar foot sensitivity and balance control of ADHD (n = 21) impaired children compared to age-matched healthy controls (n = 25). Thresholds were measured at 200 Hz at three anatomical locations of the plantar foot area of both feet (hallux, first metatarsal head (METI) and heel). Body balance was…

  14. Lung mast cells and hypoxic pulmonary vasoconstriction in cats

    Energy Technology Data Exchange (ETDEWEB)

    Martin, L.F.; Tucker, A.; Munroe, M.L.; Reeves, J.T.

    1978-01-01

    An attempt was made to reduce or eliminate lung mast cells in order to determine the involvement of mast cells in hypoxic pulmonary vasoconstriction. Anesthetized cats were exposed to acute hypoxia (10% O/sub 2/) 20 to 24 h after no pretreatment, after total lung irradiation (3,000 r), after intravenous nitrogen mustard, or after combined lung irradiation and nitrogen mustard. None of the treatments reduced total or perivascular lung mast cell density, or reduced the pulmonary vasoconstrictor response to hypoxia. However, an inverse relationship between lung mast cell density and the pulmonary pressor response to hypoxia was observed. These results suggest that the presence of more lung mast cells may oppose hypoxic pulmonary vasoconstriction.

  15. NEUROGENETIC ASPECTS OF PERINATAL HYPOXIC-ISCHEMIC AFFECTIONS OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    G. A. Karkashadze

    2016-01-01

    Full Text Available Neurogenetics is a thriving young science greatly contributing to the generally accepted concept of the brain development in health and disease. Thereby; scientists are not only able to highlight new key points in traditional ideas about the origin of diseases; but also to completely rethink their view on the problem of pathology development. In particular; new data on neurogenetics of perinatal affections of the central nervous system (CNS has appeared. Genetic factors in varying degrees affect perinatal hypoxic-ischemic CNS affections. Prematurity determination stays the most studied among them. Nevertheless; there is increasing evidence of significant epigenetic regulations of neuro-expression caused by hypoxia; malnutrition of a pregnant woman; stress; smoking; alcohol; drugs that either directly pathologically affect the developing brain; or form a brain phenotype sensitive to a perinatal CNS affection. New data obliges to change the approaches to prevention of perinatal CNS affections.

  16. Apparent diffusion coefficient histogram analysis of neonatal hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Cauley, Keith A. [University of Massachusetts Medical School, Department of Radiology, Worcester, MA (United States); New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States); Filippi, Christopher G. [New York Presbyterian Hospital, Columbia University Medical Center, Department of Radiology, New York, NY (United States)

    2014-06-15

    Diffusion-weighted imaging is a valuable tool in the assessment of the neonatal brain, and changes in diffusion are seen in normal development as well as in pathological states such as hypoxic-ischemic encephalopathy (HIE). Various methods of quantitative assessment of diffusion values have been reported. Global ischemic injury occurring during the time of rapid developmental changes in brain myelination can complicate the imaging diagnosis of neonatal HIE. To compare a quantitative method of histographic analysis of brain apparent coefficient (ADC) maps to the qualitative interpretation of routine brain MR imaging studies. We correlate changes in diffusion values with gestational age in radiographically normal neonates, and we investigate the sensitivity of the method as a quantitative measure of hypoxic-ischemic encephalopathy. We reviewed all brain MRI studies from the neonatal intensive care unit (NICU) at our university medical center over a 4-year period to identify cases that were radiographically normal (23 cases) and those with diffuse, global hypoxic-ischemic encephalopathy (12 cases). We histographically displayed ADC values of a single brain slice at the level of the basal ganglia and correlated peak (s-sD{sub av}) and lowest histogram values (s-sD{sub lowest}) with gestational age. Normative s-sD{sub av} values correlated significantly with gestational age and declined linearly through the neonatal period (r {sup 2} = 0.477, P < 0.01). Six of 12 cases of known HIE demonstrated significantly lower s-sD{sub av} and s-sD{sub lowest} ADC values than were reflected in the normative distribution; several cases of HIE fell within a 95% confidence interval for normative studies, and one case demonstrated higher-than-normal s-sD{sub av}. Single-slice histographic display of ADC values is a rapid and clinically feasible method of quantitative analysis of diffusion. In this study normative values derived from consecutive neonates without radiographic evidence of

  17. β-GPA treatment leads to elevated basal metabolic rate and enhanced hypoxic exercise tolerance in mice.

    Science.gov (United States)

    Ross, Trenton T; Overton, Jeffrey D; Houmard, Katelyn F; Kinsey, Stephen T

    2017-03-01

    Treatments that increase basal metabolic rate (BMR) and enhance exercise capacity may be useful therapeutic approaches for treating conditions such as type 2 diabetes, obesity, and associated circulatory problems. β-guanidinopropionic acid (β-GPA) supplementation decreases high-energy phosphate concentrations, such as ATP and phosphocreatine (PCr) resulting in an energetic challenge that is similar to both exercise programs and hypoxic conditions. In this study, we administered β-GPA to mice for 2 or 6 weeks, and investigated the effect on muscle energetic status, body and muscle mass, muscle capillarity, BMR, and normoxic and hypoxic exercise tolerance (NET and HET, respectively). Relative [PCr] and PCr/ATP ratios significantly decreased during both treatment times in the β-GPA fed mice compared to control mice. Body mass, muscle mass, and muscle fiber size significantly decreased after β-GPA treatment, whereas muscle capillarity and BMR were significantly increased in β-GPA fed mice. NET significantly decreased in the 2-week treatment, but was not significantly different in the 6-week treatment. HET significantly decreased in 2-week treatment, but in contrast to NET, significantly increased in the 6-week-treated mice compared to control mice. We conclude that β-GPA induces a cellular energetic response in skeletal muscle similar to that of chronic environmental hypoxia, and this energetic perturbation leads to elevated BMR and increased hypoxic exercise capacity in the absence of hypoxic acclimation. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  18. Improved PID controller design for unstable time delay processes based on direct synthesis method and maximum sensitivity

    Science.gov (United States)

    Vanavil, B.; Krishna Chaitanya, K.; Seshagiri Rao, A.

    2015-06-01

    In this paper, a proportional-integral-derivative controller in series with a lead-lag filter is designed for control of the open-loop unstable processes with time delay based on direct synthesis method. Study of the performance of the designed controllers has been carried out on various unstable processes. Set-point weighting is considered to reduce the undesirable overshoot. The proposed scheme consists of only one tuning parameter, and systematic guidelines are provided for selection of the tuning parameter based on the peak value of the sensitivity function (Ms). Robustness analysis has been carried out based on sensitivity and complementary sensitivity functions. Nominal and robust control performances are achieved with the proposed method and improved closed-loop performances are obtained when compared to the recently reported methods in the literature.

  19. Neonatal seizures and therapeutic hypothermia for hypoxic-ischemic encephalopathy

    OpenAIRE

    2014-01-01

    Neonatal seizures are associated with morbidity and mortality. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of seizures in newborns. Neonatal animal models suggest that therapeutic hypothermia can reduce seizures and epileptiform activity in the setting of hypoxia-ischemia, however data from human studies have conflicting results. In this research highlight, we will discuss the findings of our recent study that demonstrated a decreased seizure burden in term newborns with mo...

  20. Excess post hypoxic oxygen consumption in Atlantic cod (Gadus morhua)

    DEFF Research Database (Denmark)

    Plambech, M.; Deurs, Mikael van; Steffensen, J.F.;

    2013-01-01

    Atlantic cod Gadus morhua experienced oxygen deficit (DO2 ) when exposed to oxygen levels below their critical level (c. 73% of pcrit) and subsequent excess post-hypoxic oxygen consumption (CEPHO) upon return to normoxic conditions, indicative of an oxygen debt. The mean±s.e. CEPHO:DO2 was 6·9±1·......·9±1·5, suggesting that resorting to anaerobic energy production in severe hypoxia is energetically expensive...

  1. Excess post hypoxic oxygen consumption in Atlantic cod (Gadus morhua)

    DEFF Research Database (Denmark)

    Plambech, M.; Deurs, Mikael van; Steffensen, J.F.

    2013-01-01

    Atlantic cod Gadus morhua experienced oxygen deficit (DO2 ) when exposed to oxygen levels below their critical level (c. 73% of pcrit) and subsequent excess post-hypoxic oxygen consumption (CEPHO) upon return to normoxic conditions, indicative of an oxygen debt. The mean±s.e. CEPHO:DO2 was 6......·9±1·5, suggesting that resorting to anaerobic energy production in severe hypoxia is energetically expensive...

  2. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study.

    Directory of Open Access Journals (Sweden)

    Stuart Currie

    Full Text Available BACKGROUND: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1 to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2 to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. MATERIALS & METHODS: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. RESULTS: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. CONCLUSIONS: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar

  3. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

    Directory of Open Access Journals (Sweden)

    Hiroshi Sameshima

    2013-01-01

    Full Text Available Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

  4. Transcriptome analysis of severe hypoxic stress during development in zebrafish

    Directory of Open Access Journals (Sweden)

    I.G. Woods

    2015-12-01

    Full Text Available Hypoxia causes critical cellular injury both in early human development and in adulthood, leading to cerebral palsy, stroke, and myocardial infarction. Interestingly, a remarkable phenomenon known as hypoxic preconditioning arises when a brief hypoxia exposure protects target organs against subsequent, severe hypoxia. Although hypoxic preconditioning has been demonstrated in several model organisms and tissues including the heart and brain, its molecular mechanisms remain poorly understood. Accordingly, we used embryonic and larval zebrafish to develop a novel vertebrate model for hypoxic preconditioning, and used this model to identify conserved hypoxia-regulated transcripts for further functional study as published in Manchenkov et al. (2015 in G3: Genes|Genomes|Genetics. In this Brief article, we provide extensive annotation for the most strongly hypoxia-regulated genes in zebrafish, including their human orthologs, and describe in detail the methods used to identify, filter, and annotate hypoxia-regulated transcripts for downstream functional and bioinformatic assays using the source data provided in Gene Expression Omnibus Accession GSE68473.

  5. Anti hypoxic and antioxidant activity of Hibiscus esculentus seeds

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimzadeh, M. A.; Nabavi, S. F.; Nabavi, S. M.; Eslami, B.

    2010-07-01

    The anti hypoxic and antioxidant activities of Hibiscus esculentus seeds were investigated employing eight in vitro assay systems. Anti hypoxic activity was investigated in two models, haemic and circulatory. The effects were pronounced in both models of hypoxia. The anti hypoxic effects were dose-dependent. The results indicated that the extracts have a protective effect against hypoxia induced lethality in mice. The extracts showed antioxidant activity in some models. IC{sub 5}0 for DPPH radical-scavenging activity was 234 {+-} 8.9 {mu}g ml{sup 1}. The extracts showed weak nitric oxide-scavenging activity between 0.1 and 1.6 mg ml{sup -}1. The extracts showed weak Fe{sup 2}+ chelating ability. IC{sub 5}0 were 150 {+-} 13 {mu}g ml{sup -}1. The extracts also exhibited low antioxidant activity in the linoleic acid model but were capable of scavenging hydrogen peroxide in a concentration dependent manner. The total amount of phenolic compounds in each extract was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. Pharmacological effects may be attributed, at least in part, to the presence of phenols and flavonoids in the extracts. (Author) 40 refs.

  6. H-infinity mix sensitivity controller design based on GIMC for electro-optical stabilization and tracking system

    Science.gov (United States)

    Liu, Zi-dong; Bao, Qi-liang; Xia, Yunxia; Liu, Xiang

    2013-08-01

    Electro-optical stabilization and tracking system is critical and difficult issue in satellite laser communication. Moreover, line-of-sight stabilized system is the kernel of implementing electro-optical stabilization and tracking system, which can be used to isolate the vibration of the moving platform of the satellite and the disturbance of the space environment. In this paper, we propose a new method, which using H∞ mix sensitivity based on generalized internal model controller (GIMC), to design the control system of the electro-optical stabilized platform. It is well known that there is an intrinsic conflict between performance and robustness in the standard feedback framework. Generalized internal model controller is a new architecture which can separate the performance and robustness design in controller design. This architecture has two parts: a high performance controller, say K0,which is designed by PI controller in this paper, and then a robustification controller, say Q, which is designed to improve the ability of the anti disturbance by using H-infinity mix sensitivity controller design method. In this paper, we also present the steps of controller design by using this method to make it easier to use. Based on the proposed method, numerical simulation and experiment are both carried out for a gyro stabilized platform of electro-optical tacking system. Both the numerical simulated and the experimental results show that the electro-optical stabilized platform using the H-infinity mix sensitivity controller design method based on GIMC is accurate and effective. Comparing with the same PI controller in standard feedback framework, the proposed method can guarantee the high tracking performance as same as the PI controller and improve the external disturbance restraining ability a lot. In conclusion, H-infinity mix sensitivity controller design method based on GIMC is a new approach for gyro stabilized platform of electro-optical stabilization and tracking

  7. Final report on the United States phase I clinical trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC No. 261037

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, T.L. (Univ. of California, San Francisco); Wasserman, T.H.; Johnson, R.J.; Levin, V.A.; VanRaalte, G.

    1981-10-15

    The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1 to 5 g/m. The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared to lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose-limiting toxicity is neurologic.

  8. Potential application of thermo-sensitive hydrogels for controlled release of phenacetin

    Directory of Open Access Journals (Sweden)

    Ilić-Stojanović Snežana S.

    2012-01-01

    Full Text Available Over the past years, many scientific researches have been focused on thermo-sensitive hydrogels containing N-isopropylacrylamide (NIPAM as a monomer. The NIPAM based hydrogels with 20 mol% 2-hydroxypropyl methacrylate (HPMet were synthesized using ethylene glycol dimethacrylate as a cross-linker. The characterization of xerogel and phenacetin using FTIR spectra and SEM micrographs confirm the performed synthesis with satisfactory purity as well as loading of phenacetin into hydrogel. The swelling transport mechanism at simulated physiological conditions (pH 2.20 and 7.40 at 37°C is described by the time-independent kinetics. The potential application of synthesized hydrogels for the controlled release of phenacetin as a model drug was investigated at simulated physiological conditions by HPLC method. [Acknowledgement. This work is part of the project MNTR TR-34012 financed by the Ministry of Education and Science of the Republic of Serbia. The authors are grateful for the support provided by the Ministry.

  9. Stability and Sensitivity Analysis of a Plant Disease Model with Continuous Cultural Control Strategy

    Directory of Open Access Journals (Sweden)

    Zhang Zhonghua

    2014-01-01

    Full Text Available In this paper, a plant disease model with continuous cultural control strategy and time delay is formulated. Then, how the time delay affects the overall disease progression and, mathematically, how the delay affects the dynamics of the model are investigated. By analyzing the transendental characteristic equation, stability conditions related to the time delay are derived for the disease-free equilibrium. Specially, when R0=1, the Jacobi matrix of the model at the disease-free equilibrium always has a simple zero eigenvalue for all τ≥0. The center manifold reduction and the normal form theory are used to discuss the stability and the steady-state bifurcations of the model near the nonhyperbolic disease-free equilibrium. Then, the sensitivity analysis of the threshold parameter R0 and the positive equilibrium E* is carried out in order to determine the relative importance of different factors responsible for disease transmission. Finally, numerical simulations are employed to support the qualitative results.

  10. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  11. Inhibitory Control of Feature Selectivity in an Object Motion Sensitive Circuit of the Retina

    Directory of Open Access Journals (Sweden)

    Tahnbee Kim

    2017-05-01

    Full Text Available Object motion sensitive (OMS W3-retinal ganglion cells (W3-RGCs in mice respond to local movements in a visual scene but remain silent during self-generated global image motion. The excitatory inputs that drive responses of W3-RGCs to local motion were recently characterized, but which inhibitory neurons suppress W3-RGCs’ responses to global motion, how these neurons encode motion information, and how their connections are organized along the excitatory circuit axis remains unknown. Here, we find that a genetically identified amacrine cell (AC type, TH2-AC, exhibits fast responses to global motion and slow responses to local motion. Optogenetic stimulation shows that TH2-ACs provide strong GABAA receptor-mediated input to W3-RGCs but only weak input to upstream excitatory neurons. Cell-type-specific silencing reveals that temporally coded inhibition from TH2-ACs cancels W3-RGC spike responses to global but not local motion stimuli and, thus, controls the feature selectivity of OMS signals sent to the brain.

  12. Adipocyte SIRT1 controls systemic insulin sensitivity by modulating macrophages in adipose tissue.

    Science.gov (United States)

    Hui, Xiaoyan; Zhang, Mingliang; Gu, Ping; Li, Kuai; Gao, Yuan; Wu, Donghai; Wang, Yu; Xu, Aimin

    2017-04-01

    Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD(+)-dependent deacetylase SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance. The phenotypic changes in adipocyte-selective SIRT1 knockout mice are associated with an increased number of adipose-resident macrophages and their polarization toward the pro-inflammatory M1 subtype. Mechanistically, SIRT1 in adipocytes modulates expression and secretion of several adipokines, including adiponectin, MCP-1, and interleukin 4, which in turn alters recruitment and polarization of the macrophages in adipose tissues. In adipocytes, SIRT1 deacetylates the transcription factor NFATc1 and thereby enhances the binding of NFATc1 to the Il4 gene promoter. These findings suggest that adipocyte SIRT1 controls systemic glucose homeostasis and insulin sensitivity via the cross talk with adipose-resident macrophages. © 2017 The Authors.

  13. Controlling the magnetic field sensitivity of atomic clock states by microwave dressing

    CERN Document Server

    Sárkány, L; Hattermann, H; Fortágh, J

    2014-01-01

    We demonstrate control of the differential Zeeman shift between clock states of ultracold rubidium atoms by means of non-resonant microwave dressing. Using the dc-field dependence of the microwave detuning, we suppress the first and second order differential Zeeman shift in magnetically trapped $^{87}$Rb atoms. By dressing the state pair 5S$_{1/2} F= 1, m_F = -1$ and $F= 2, m_F = 1$, a residual frequency spread of <0.1 Hz in a range of 100 mG around a chosen magnetic offset field can be achieved. This is one order of magnitude smaller than the shift of the bare states at the magic field of the Breit-Rabi parabola. We further identify double magic points, around which the clock frequency is insensitive to fluctuations both in the magnetic field and the dressing Rabi frequency. The technique is compatible with chip-based cold atom systems and allows the creation of clock and qubit states with reduced sensitivity to magnetic field noise.

  14. Design of satisfaction output feedback controls for stochastic nonlinear systems under quadratic tracking risk-sensitive index

    Institute of Scientific and Technical Information of China (English)

    刘允刚; 张纪峰; 潘子刚

    2003-01-01

    In this paper, the design problem of satisfaction output feedback controls for stochastic nonlinear systems in strict feedback form under long-term tracking risk-sensitive index is investigated.The index function adopted here is of quadratic form usually encountered in practice, rather than of quartic one used to beg the essential difficulty on controller design and performance analysis of the closed-loop systems. For any given risk-sensitive parameter and desired index value, by using the integrator backstepping method, an output feedback control is constructively designed so that the closed-loop system is bounded in probability and the risk-sensitive index is upper bounded by the desired value.

  15. Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang JIANG; Ai-Guo DAI; Qi-Fang LI; Rui-Cheng HU

    2006-01-01

    The muscularization of non-muscular pulmonary arterioles is animportant pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-β 1 (TGF-β 1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of α-smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-β1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

  16. Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements.

    Science.gov (United States)

    Firth, J D; Ebert, B L; Ratcliffe, P J

    1995-09-08

    The oxygen-regulated control system responsible for the induction of erythropoietin (Epo) by hypoxia is present in most (if not all) cells and operates on other genes, including those involved in energy metabolism. To understand the organization of cis-acting sequences that are responsible for oxygen-regulated gene expression, we have studied the 5' flanking region of the mouse gene encoding the hypoxically inducible enzyme lactate dehydrogenase A (LDH). Deletional and mutational analysis of the function of mouse LDH-reporter fusion gene constructs in transient transfection assays defined three domains, between -41 and -84 base pairs upstream of the transcription initiation site, which were crucial for oxygen-regulated expression. The most important of these, although not capable of driving hypoxic induction in isolation, had the consensus of a hypoxia-inducible factor 1 (HIF-1) site, and cross-competed for the binding of HIF-1 with functionally active Epo and phosphoglycerate kinase-1 sequences. The second domain was positioned close to the HIF-1 site, in an analogous position to one of the critical regions in the Epo 3' hypoxic enhancer. The third domain had the motif of a cAMP response element (CRE). Activation of cAMP by forskolin had no effect on the level of LDH mRNA in normoxia, but produced a magnified response to hypoxia that was dependent upon the integrity of the CRE, indicating an interaction between inducible factors binding the HIF-1 and CRE sites.

  17. Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Pilgaard, L.; Lund, P.; Duroux, M. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Lockstone, H.; Taylor, J. [Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Emmersen, J.; Fink, T. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Ragoussis, J. [Genomics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Zachar, V., E-mail: vlaz@hst.aau.dk [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)

    2009-07-01

    Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

  18. pH-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release

    Directory of Open Access Journals (Sweden)

    Wang SL

    2012-11-01

    Full Text Available Wen-Yu Qian,1,* Dong-Mei Sun,1,* Rong-Rong Zhu,1 Xi-Ling Du,1 Hui Liu,2 Shi-Long Wang11Shanghai Tenth People's Hospital, School of Life Science and Technology, Tongji University, Shanghai, PR China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, PR China*Wen-Yu Qian and Dong-Mei Sun contributed equally to this workAbstract: Strontium carbonate nanoparticles (SCNs, a novel biodegradable nanosystem for the pH-sensitive release of anticancer drugs, were developed via a facile mixed solvent method aimed at creating smart drug delivery in acidic conditions, particularly in tumor environments. Structural characterization of SCNs revealed that the engineered nanocarriers were uniform in size and presented a dumbbell-shaped morphology with a dense mass of a scale-like spine coating, which could serve as the storage structure for hydrophobic drugs. Chosen as a model anticancer agent, etoposide was effectively loaded into SCNs based on a simultaneous process that allowed for the formation of the nanocarriers and for drug storage to be accomplished in a single step. The etoposide-loaded SCNs (ESCNs possess both a high loading capacity and efficient encapsulation. It was found that the cumulative release of etoposide from ESCNs is acid-dependent, and that the release rate is slow at a pH of 7.4; this rate increases significantly at low pH levels (5.8, 3.0. Meanwhile, it was also found that the blank SCNs were almost nontoxic to normal cells, and ESCN systems were evidently more potent in antitumor activity compared with free etoposide, as confirmed by a cytotoxicity test using an MTT assay and an apoptosis test with fluorescence-activated cell sorter (FACS analysis. These findings suggest that SCNs hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.Keywords: strontium carbonate, nanoparticles, pH-sensitive drug delivery, etoposide, anticancer activity

  19. Enzymatic- and temperature-sensitive controlled release of ultrasmall superparamagnetic iron oxides (USPIOs

    Directory of Open Access Journals (Sweden)

    Ortega Ryan A

    2011-02-01

    Full Text Available Abstract Background Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs that sense enzymatic activity for applications in magnetic resonance imaging (MRI. To achieve this goal, we utilize amphiphilic poly(propylene sulfide-bl-poly(ethylene glycol (PPS-b-PEG copolymers, which are known to have excellent properties for smart delivery of drug and siRNA. Results Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R2 negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature. Conclusions This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that

  20. Hypoxic pulmonary vasodilation: a paradigm shift with a hydrogen sulfide mechanism

    National Research Council Canada - National Science Library

    Kenneth R. Olson; Nathan L. Whitfield; Shawn E. Bearden; Judy St. Leger; Erika Nilson; Yan Gao; Jane A. Madden

    2010-01-01

    Hypoxic pulmonary vasoconstriction (HVC), an intrinsic and assumed ubiquitous response of mammalian pulmonary blood vessels, matches regional ventilation to perfusion via an unknown O2-sensing mechanism...

  1. Reward and punishment sensitivity and alcohol use : The moderating role of executive control

    NARCIS (Netherlands)

    Jonker, Nienke C.; Ostafin, Brian D.; Glashouwer, Klaske A.; van Hemel-Ruiter, Madelon E.; de Jong, Peter J.

    2014-01-01

    Reward sensitivity and to a lesser extent punishment sensitivity have been found to explain individual differences in alcohol use. Furthermore, many studies showed that addictive behaviors are characterized by impaired self-regulatory processes, and that individual differences related to alcohol use

  2. Reward and punishment sensitivity and alcohol use : The moderating role of executive control

    NARCIS (Netherlands)

    Jonker, Nienke C.; Ostafin, Brian D.; Glashouwer, Klaske A.; Ruiter, Madelon E.; de Jong, Peter J.

    2015-01-01

    Reward sensitivity and to a lesser extent punishment sensitivity have been found to explain individual differences in alcohol use. Furthermore, many studies showed that addictive behaviors are characterized by impaired self-regulatory processes, and that individual differences related to alcohol use

  3. Reward and punishment sensitivity and alcohol use : The moderating role of executive control

    NARCIS (Netherlands)

    Jonker, Nienke C.; Ostafin, Brian D.; Glashouwer, Klaske A.; van Hemel-Ruiter, Madelon E.; de Jong, Peter J.

    2014-01-01

    Reward sensitivity and to a lesser extent punishment sensitivity have been found to explain individual differences in alcohol use. Furthermore, many studies showed that addictive behaviors are characterized by impaired self-regulatory processes, and that individual differences related to alcohol use

  4. Reward and punishment sensitivity and alcohol use : The moderating role of executive control

    NARCIS (Netherlands)

    Jonker, Nienke C.; Ostafin, Brian D.; Glashouwer, Klaske A.; Ruiter, Madelon E.; de Jong, Peter J.

    2015-01-01

    Reward sensitivity and to a lesser extent punishment sensitivity have been found to explain individual differences in alcohol use. Furthermore, many studies showed that addictive behaviors are characterized by impaired self-regulatory processes, and that individual differences related to alcohol use

  5. SU-E-T-146: Effects of Uncertainties of Radiation Sensitivity of Biological Modelling for Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Oita, M [Department of Radiological Technology, Graduate School of Health Sciences, Okayama University (Japan); Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Uto, Y; Hori, H [Department of Life System, Institute of Technology and Science, Graduate School, The Tokushima University (Japan); Tominaga, M [Department of Radiological Technology, Institute of Health Biosciences, Graduate School, The Tokushima University (Japan); Sasaki, M [Department of Radiology, Tokushima University Hospital (Japan)

    2014-06-01

    Purpose: The aim of this study was to evaluate the distribution of uncertainty of cell survival by radiation, and assesses the usefulness of stochastic biological model applying for gaussian distribution. Methods: For single cell experiments, exponentially growing cells were harvested from the standard cell culture dishes by trypsinization, and suspended in test tubes containing 1 ml of MEM(2x10{sup 6} cells/ml). The hypoxic cultures were treated with 95% N{sub 2}−5% CO{sub 2} gas for 30 minutes. In vitro radiosensitization was also measured in EMT6/KU single cells to add radiosensitizer under hypoxic conditions. X-ray irradiation was carried out by using an Xray unit (Hitachi X-ray unit, model MBR-1505R3) with 0.5 mm Al/1.0 mm Cu filter, 150 kV, 4 Gy/min). In vitro assay, cells on the dish were irradiated with 1 Gy to 24 Gy, respectively. After irradiation, colony formation assays were performed. Variations of biological parameters were investigated at standard cell culture(n=16), hypoxic cell culture(n=45) and hypoxic cell culture(n=21) with radiosensitizers, respectively. The data were obtained by separate schedule to take account for the variation of radiation sensitivity of cell cycle. Results: At standard cell culture, hypoxic cell culture and hypoxic cell culture with radiosensitizers, median and standard deviation of alpha/beta ratio were 37.1±73.4 Gy, 9.8±23.7 Gy, 20.7±21.9 Gy, respectively. Average and standard deviation of D{sub 50} were 2.5±2.5 Gy, 6.1±2.2 Gy, 3.6±1.3 Gy, respectively. Conclusion: In this study, we have challenged to apply these uncertainties of parameters for the biological model. The variation of alpha values, beta values, D{sub 50} as well as cell culture might have highly affected by probability of cell death. Further research is in progress for precise prediction of the cell death as well as tumor control probability for treatment planning.

  6. PH Sensitive Polymers for Improving Reservoir Sweep and Conformance Control in Chemical Flooring

    Energy Technology Data Exchange (ETDEWEB)

    Mukul Sharma; Steven Bryant; Chun Huh

    2008-03-31

    viscoelastic behavior as functions of pH; shear rate; polymer concentration; salinity, including divalent ion effects; polymer molecular weight; and degree of hydrolysis. A comprehensive rheological model was developed for HPAM solution rheology in terms of: shear rate; pH; polymer concentration; and salinity, so that the spatial and temporal changes in viscosity during the polymer flow in the reservoir can be accurately modeled. A series of acid coreflood experiments were conducted to understand the geochemical reactions relevant for both the near-wellbore injection profile control and for conformance control applications. These experiments showed that the use hydrochloric acid as a pre-flush is not viable because of the high reaction rate with the rock. The use of citric acid as a pre-flush was found to be quite effective. This weak acid has a slow rate of reaction with the rock and can buffer the pH to below 3.5 for extended periods of time. With the citric acid pre-flush the polymer could be efficiently propagated through the core in a low pH environment i.e. at a low viscosity. The transport of various HPAM solutions was studied in sandstones, in terms of permeability reduction, mobility reduction, adsorption and inaccessible pore volume with different process variables: injection pH, polymer concentration, polymer molecular weight, salinity, degree of hydrolysis, and flow rate. Measurements of polymer effluent profiles and tracer tests show that the polymer retention increases at the lower pH. A new simulation capability to model the deep-penetrating mobility control or conformance control using pH-sensitive polymer was developed. The core flood acid injection experiments were history matched to estimate geochemical reaction rates. Preliminary scale-up simulations employing linear and radial geometry floods in 2-layer reservoir models were conducted. It is clearly shown that the injection rate of pH-sensitive polymer solutions can be significantly increased by injecting

  7. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Timothy R Crother

    Full Text Available Chlamydia pneumoniae (CP is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate, but not a high dose (severe CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n. with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

  8. Chlamydia pneumoniae infection induced allergic airway sensitization is controlled by regulatory T-cells and plasmacytoid dendritic cells.

    Science.gov (United States)

    Crother, Timothy R; Schröder, Nicolas W J; Karlin, Justin; Chen, Shuang; Shimada, Kenichi; Slepenkin, Anatoly; Alsabeh, Randa; Peterson, Ellena; Arditi, Moshe

    2011-01-01

    Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2-/-, and TLR4-/- mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2-/- mice, but not in TLR4-/- mice, due to differential Treg responses in these genotypes. TLR2-/- mice had reduced numbers of Tregs in the lung during CP infection while TLR4-/- mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.

  9. The Performance and Feasibility of Ensemble Forecast Sensitivity to Observations-based Proactive Quality Control Scheme

    Science.gov (United States)

    Chen, T. C.; Hotta, D.; Kalnay, E.

    2015-12-01

    Operational numerical weather prediction (NWP) systems occasionally exhibit "forecast skill dropouts" in which the forecast skill drops to an abnormally low level, due in part to the assimilation of flawed observational data. Recent studies have shown that a diagnostic technique called Ensemble Forecast Sensitivity to Observations (EFSO) can detect such observations (Kalnay et.al 2012; Ota et al. 2013, Tellus A). Based on this technique, a new Quality Control (QC) scheme called Proactive QC (PQC) has been proposed which detects "flawed" observations using EFSO after just 6 hours forecast, when the analysis at the next cycle becomes available for verification and then repeats the analysis and forecast without using the detected observations (Hotta 2014). In Hotta (2014), it was shown using the JCSDA S4 Testbed that the 6hr PQC reduces the 24-hour forecast errors from the detected skill dropout events. With such encouraging results we are performing preliminary experiments towards operational implementation. First, we show that offline PQC correction can significantly reduce forecast errors up to 5 days, and that the reduction and improved areal coverage can grow with synoptic weather disturbances for several days. Second, with online PQC cycle experiment the reduction of forecast error is shown to be even larger than in the offline version, since the effect could accumulate over each time we perform a PQC correction. Finally, the operational center imposes very tight schedule in order to deliver the products on time, thus the computational cost has to be minimized in order for PQC to be implemented. To avoid performing the analysis twice, which is the most expensive part of PQC, we test the accuracy of constant-K approximation, which assumes the Kalman gain K doesn't change much given the fact that only a small subset of observation is rejected. In this presentation, we will demonstrate the performance and feasibility of PQC implementation in real-time operational

  10. Photo-sensitive Ge nanocrystal based films controlled by substrate deposition temperature

    KAUST Repository

    Stavarache, Ionel

    2017-07-21

    Lowering the temperature of crystallization by deposition of thin films on a heated substrate represents the easiest way to find new means to develop and improve new working devices based on nanocrystals embedded in thin films. The improvements are strongly related with the increasing of operation speed, substantially decreasing the energy consumption and reducing unit fabrication costs of the respective semiconductor devices. This approach avoids major problems, such as those related to diffusion or difficulties in controlling of nanocrystallites size, which appear during thermal treatments at high temperatures after deposition. It is reported here the significant progress introduced by synthesis procedure to the in-situ structuring of Ge nanocrystallites in SiO2 thin films by heating the substrate at low temperature, 400 °C during co-deposition of Ge and SiO2 by magnetron sputtering. As a proof-of-concept, a Si/Ge-NCs:SiO2 photo-sensitive structure was fabricated thereof and characterized. The structure shows superior performance on broad operation bandwidth from visible to near-infrared, as strong rectification properties in dark, significant current rise in the inversion mode when illuminated, high responsivity, high photo-detectivity of 1014 Jones, quick response and significant conversion efficiency of 850 %. This simple preparation approach brings an important contribution to the efort of structuring Ge nanocrystallites in SiO2 thin films at a lower temperature for the purpose of using these materials for devices in optoelectronics, solar cells and electronics on flexible substrates.

  11. Exploring the intricate regulatory network controlling the thiazide-sensitive NaCl cotransporter (NCC).

    Science.gov (United States)

    Dimke, Henrik

    2011-12-01

    The thiazide-sensitive NaCl cotransporter (NCC) plays key roles in renal electrolyte transport and blood pressure maintenance. Regulation of this cotransporter has received increased attention recently, prompted by the discovery that mutations in the with-no-lysine (WNK) kinases are the molecular explanation for pseudohypoaldosteronism type II (PHAII). Studies suggest that WNK4 regulates NCC via two distinct pathways, depending on its state of activation. Furthermore, an intact STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response 1 kinase (OSR1) pathway was found to be necessary for a WNK4 PHAII mutation to increase NCC phosphorylation and blood pressure in mice. The mouse protein 25α is a novel regulator of the SPAK/OSR1 kinase family, which greatly increases their activity. The phosphorylation status of NCC and the WNK is regulated by the serum- and glucocorticoid-inducible kinase 1, suggesting novel mechanisms whereby aldosterone modulates NCC activity. Dephosphorylation of NCC by protein phosphatase 4 strongly influences the activity of the cotransporter, confirming an important role for NCC phosphorylation. Finally, γ-adducin increases NCC activity. This stimulatory effect is dependent on the phosphorylation status of the cotransporter. γ-Adducin only binds the dephosphorylated cotransporter, suggesting that phosphorylation of NCC causes the dissociation of γ-adducin. Since γ-adducin is not a kinase, it is tempting to speculate that the protein exerts its function by acting as a scaffold between the dephosphorylated cotransporter and the regulatory kinase. As more molecular regulators of NCC are identified, the system-controlling NCC activity is becoming increasingly complex. This intricacy confers an ability to integrate a variety of stimuli, thereby regulating NCC transport activity and ultimately blood pressure.

  12. Mineralization of bone-related SaOS-2 cells under physiological hypoxic conditions.

    Science.gov (United States)

    Müller, Werner E G; Schröder, Heinz C; Tolba, Emad; Diehl-Seifert, Bärbel; Wang, Xiaohong

    2016-01-01

    Inorganic polyphosphate (polyP) is a physiological energy-rich polymer with multiple phosphoric anhydride bonds. In cells such as bone-forming osteoblasts, glycolysis is the main pathway generating metabolic energy in the form of ATP. In the present study, we show that, under hypoxic culture conditions, the growth/viability of osteoblast-like SaOS-2 cells is not impaired. The addition of polyP to those cells, administered as amorphous calcium polyP nanoparticles (aCa-polyP-NP; approximate size 100 nm), significantly increased the proliferation of the cells. In the presence of polyP, the cells produce significant levels of lactate, the end product of anaerobic glycolysis. Under those conditions, an eight-fold increase in the steady-state level of the membrane-associated carbonic anhydrase IX is found, as well as a six-fold induction of the hypoxia-inducible factor 1. Consequently, biomineral formation onto the SaOS-2 cells decreases under low oxygen tension. If the polyP nanoparticles are added to the cells, the degree of mineralization is enhanced. These changes had been measured also in human mesenchymal stem cells. The assumption that the bicarbonate, generated by the carbonic anhydrase in the presence of polyP under low oxygen, is deposited as a constituent of the bioseeds formed during initial hydroxyapatite formation is corroborated by the identification of carbon besides of calcium, oxygen and phosphorus in the initial biomineral deposit onto the cells using the sensitive technology of high-resolution energy dispersive spectrometry mapping. Based on these data, we conclude that polyP is required for the supply of metabolic energy during bone mineral formation under physiological, hypoxic conditions, acting as a 'metabolic fuel' for the cells to grow.

  13. PH Sensitive Polymers for Improving Reservoir Sweep and Conformance Control in Chemical Flooring

    Energy Technology Data Exchange (ETDEWEB)

    Mukul Sharma; Steven Bryant; Chun Huh

    2008-03-31

    viscoelastic behavior as functions of pH; shear rate; polymer concentration; salinity, including divalent ion effects; polymer molecular weight; and degree of hydrolysis. A comprehensive rheological model was developed for HPAM solution rheology in terms of: shear rate; pH; polymer concentration; and salinity, so that the spatial and temporal changes in viscosity during the polymer flow in the reservoir can be accurately modeled. A series of acid coreflood experiments were conducted to understand the geochemical reactions relevant for both the near-wellbore injection profile control and for conformance control applications. These experiments showed that the use hydrochloric acid as a pre-flush is not viable because of the high reaction rate with the rock. The use of citric acid as a pre-flush was found to be quite effective. This weak acid has a slow rate of reaction with the rock and can buffer the pH to below 3.5 for extended periods of time. With the citric acid pre-flush the polymer could be efficiently propagated through the core in a low pH environment i.e. at a low viscosity. The transport of various HPAM solutions was studied in sandstones, in terms of permeability reduction, mobility reduction, adsorption and inaccessible pore volume with different process variables: injection pH, polymer concentration, polymer molecular weight, salinity, degree of hydrolysis, and flow rate. Measurements of polymer effluent profiles and tracer tests show that the polymer retention increases at the lower pH. A new simulation capability to model the deep-penetrating mobility control or conformance control using pH-sensitive polymer was developed. The core flood acid injection experiments were history matched to estimate geochemical reaction rates. Preliminary scale-up simulations employing linear and radial geometry floods in 2-layer reservoir models were conducted. It is clearly shown that the injection rate of pH-sensitive polymer solutions can be significantly increased by injecting

  14. Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session

    Science.gov (United States)

    Dantoft, Thomas M; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Engkilde, Kaare; Lind, Nina; Nordin, Steven; Hellgren, Lars I

    2017-01-01

    Objectives To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants. The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure. Design Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure. Settings Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper. Participants 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls. Outcome measures 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels. Results MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls. Conclusions MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate

  15. Differences in Topographical Pressure Pain Sensitivity Maps of the Scalp Between Patients With Migraine and Healthy Controls.

    Science.gov (United States)

    Barón, Johanna; Ruiz, Marina; Palacios-Ceña, María; Madeleine, Pascal; Guerrero, Ángel L; Arendt-Nielsen, Lars; Fernández-de-Las-Peñas, César

    2017-02-01

    To investigate differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls considering the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the symptoms. It seems that the trigeminal area is sensitized in migraine. No study has investigated topographical pressure sensitivity maps of the scalp in patients with migraine. Pressure pain thresholds (PPTs) were assessed from 21 points distributed over the scalp in 86 patients with episodic migraine, 76 with chronic migraine, and 42 healthy age and matched healthy controls in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of migraine, anxiety, and depression (Hospital Anxiety and Depression Scale, HADS) were collected. The multivariate ANCOVA revealed significant differences in PPT between points (F = 55.674; P  .335) except for Fp1 (P = .045) and Fp2 (P = .017) points where subjects with chronic migraine had lower PPTs than those with episodic migraine; (3) no differences between bilateral/unilateral migraine (P > .417). An anterior to posterior gradient was found, with the lowest PPTs located in frontal regions and the highest PPTs in occipital areas (all groups, P pressure pain hypersensitivity in the head as compared to healthy controls and that hypersensitivity was similar between episodic/chronic and unilateral/bilateral migraine. Topographical pressure pain sensitivity maps revealed an anterior to posterior gradient of pressure pain sensitivity in both migraine and control groups. © 2016 American Headache Society.

  16. A simple and sensitive quality control method of the anaerobic atmosphere for identification and antimicrobial susceptibility testing of anaerobic bacteria

    DEFF Research Database (Denmark)

    Justesen, Tage; Justesen, Ulrik Stenz

    2013-01-01

    The maintenance of a strict anaerobic atmosphere is essential for the culture of strict anaerobic bacteria. We describe a simple and sensitive quality control method of the anaerobic atmosphere, based on the measurement of the zone diameter around a 5-μg metronidazole disk when testing an aerotol...

  17. Approximate solutions to a weighted mixed-sensitivity H-infinity-control design for irrational transfer matrices

    NARCIS (Netherlands)

    Curtain, RF; Weiss, M; Zhou, Y

    1996-01-01

    Approximate solutions to a weighted mixed-sensitivity H-infinity-control problem for an irrational transfer matrix are obtained by solving the same problem for a reduced-order (rational) transfer matrix. Upper and lower bounds are given in terms of the solution to the reduced-order problem and the a

  18. Differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls

    DEFF Research Database (Denmark)

    Barón, Johanna; Ruiz, Marina; Palacios-Ceña, María;

    2016-01-01

    OBJECTIVE: To investigate differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls considering the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the symptoms. BACKGROUND: It seems that the trigeminal a...

  19. Sensitivity to Speaker Control in the Online Comprehension of Conditional Tips and Promises: An Eye-Tracking Study

    Science.gov (United States)

    Stewart, Andrew J.; Haigh, Matthew; Ferguson, Heather J.

    2013-01-01

    Statements of the form if… then… can be used to communicate conditional speech acts such as tips and promises. Conditional promises require the speaker to have perceived control over the outcome event, whereas conditional tips do not. In an eye-tracking study, we examined whether readers are sensitive to information about perceived speaker control…

  20. Sensitivity to Speaker Control in the Online Comprehension of Conditional Tips and Promises: An Eye-Tracking Study

    Science.gov (United States)

    Stewart, Andrew J.; Haigh, Matthew; Ferguson, Heather J.

    2013-01-01

    Statements of the form if… then… can be used to communicate conditional speech acts such as tips and promises. Conditional promises require the speaker to have perceived control over the outcome event, whereas conditional tips do not. In an eye-tracking study, we examined whether readers are sensitive to information about perceived speaker control…

  1. Sirtuin 6 protects the heart from hypoxic damage

    Energy Technology Data Exchange (ETDEWEB)

    Maksin-Matveev, Anna; Kanfi, Yariv [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Hochhauser, Edith [The Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva (Israel); Isak, Ahuva; Cohen, Haim Y. [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Shainberg, Asher, E-mail: asher.shainberg@gmail.com [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel)

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension.

  2. The Determination of Feasible Control Variables for Geoengineering and Weather Modification Based on the Theory of Sensitivity in Dynamical Systems

    Directory of Open Access Journals (Sweden)

    Sergei A. Soldatenko

    2016-01-01

    Full Text Available Geophysical cybernetics allows for exploring weather and climate modification (geoengineering as an optimal control problem in which the Earth’s climate system is considered as a control system and the role of controller is given to human operators. In mathematical models used in climate studies control actions that manipulate the weather and climate can be expressed via variations in model parameters that act as controls. In this paper, we propose the “instability-sensitivity” approach that allows for determining feasible control variables in geoengineering. The method is based on the sensitivity analysis of mathematical models that describe various types of natural instability phenomena. The applicability of this technique is illustrated by a model of atmospheric baroclinic instability since this physical mechanism plays a significant role in the general circulation of the atmosphere and, consequently, in climate formation. The growth rate of baroclinic unstable waves is taken as an indicator of control manipulations. The information obtained via calculated sensitivity coefficients is very beneficial for assessing the physical feasibility of methods of control of the large-scale atmospheric dynamics and for designing optimal control systems for climatic processes. It also provides insight into potential future changes in baroclinic waves, as a result of a changing climate.

  3. Switching off malignant mesothelioma: exploiting the hypoxic microenvironment.

    Science.gov (United States)

    Nabavi, Noushin; Bennewith, Kevin L; Churg, Andrew; Wang, Yuzhuo; Collins, Colin C; Mutti, Luciano

    2016-11-01

    Malignant mesotheliomas are aggressive, asbestos-related cancers with poor patient prognosis, typically arising in the mesothelial surfaces of tissues in pleural and peritoneal cavity. The relative unspecific symptoms of mesotheliomas, misdiagnoses, and lack of precise targeted therapies call for a more critical assessment of this disease. In the present review, we categorize commonly identified genomic aberrations of mesotheliomas into their canonical pathways and discuss targeting these pathways in the context of tumor hypoxia, a hallmark of cancer known to render solid tumors more resistant to radiation and most chemo-therapy. We then explore the concept that the intrinsic hypoxic microenvironment of mesotheliomas can be Achilles' heel for targeted, multimodal therapeutic intervention.

  4. Controlled growth of semiconductor nanofilms within TiO₂ nanotubes for nanofilm sensitized solar cells.

    Science.gov (United States)

    Zheng, Xiaojia; Yu, Dongqi; Xiong, Feng-Qiang; Li, Mingrun; Yang, Zhou; Zhu, Jian; Zhang, Wen-Hua; Li, Can

    2014-04-28

    Anodized TiO2 nanotubes were decorated by II-VI semiconductor nanofilms via atomic layer deposition (ALD) and further employed as photoanodes of semiconductor nanofilm sensitized solar cells (NFSCs) exhibiting superior photovoltaic performance.

  5. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2011-12-01

    Full Text Available The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals. Although core components of the pathway are well defined, less is known about mechanisms that adjust the sensitivity of the pathway to extracellular stimuli. In humans, disturbance in insulin sensitivity leads to impaired clearance of glucose from the blood stream, which is a hallmark of diabetes. Here we present the results of a genetic screen in Drosophila designed to identify regulators of insulin sensitivity in vivo. Components of the MAPK/ERK pathway were identified as modifiers of cellular insulin responsiveness. Insulin resistance was due to downregulation of insulin-like receptor gene expression following persistent MAPK/ERK inhibition. The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels.

  6. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non-hypoxic

  7. Predictors of outcome of neonates with hypoxic ischaemic encephalopathy admitted to the neonatal unit of the University Hospital of the West Indies.

    Science.gov (United States)

    Trotman, Helen; Garbutt, Andrea

    2011-02-01

    This was a retrospective review to determine predictors of outcome in term infants with hypoxic ischaemic encephalopathy (HIE) at the University Hospital of the West Indies. Ninety-five neonates fulfilled criteria for entry into the study of these 34 (36%) had a poor outcome. The stage of encephalopathy, seizures on admission, the need for more than one antiepileptic for seizure control and an abnormal neurological examination at hospital discharge were found to be associated with poor outcome. Multiple logistic regression analyses showed that an abnormal neurological examination at discharge was the only independent predictor of poor outcome. Babies who had an abnormal neurological examination at hospital discharge were more likely to have a poor outcome (odds ratio 2.6, confidence interval 0.03-0.4). An abnormal neurological examination at discharge had a positive predictive value of 88% and a negative predictive value of 84% for poor outcome, with a sensitivity and specificity of 60 and 96%, respectively. We recommend that if post-HIE, an infant has an abnormal neurological examination at the time of discharge from hospital, that infant should be followed up and monitored in a specialist neurology clinic and parents counselled about the guarded prognosis for normal neurodevelopmental outcome.

  8. Hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries is not inhibited by antagonists of H2 S-synthesizing pathways.

    Science.gov (United States)

    Prieto-Lloret, Jesus; Shaifta, Yasin; Ward, Jeremy P T; Aaronson, Philip I

    2015-01-15

    An increase in the H2 S (hydrogen sulphide, hereafter sulphide) concentration in pulmonary artery smooth muscle cells (PASMCs) has been proposed to mediate hypoxic pulmonary vasoconstriction (HPV). We evaluated this hypothesis in isolated rat intrapulmonary arteries (IPAs) by examining the effects of the sulphide precursor cysteine and sulphide-synthesis blockers on HPV and also on normoxic pulmonary vasoconstriction (NPV) stimulated by prostaglandin F2α (PGF2α ) and by the drug LY83583, which causes contraction in IPAs by increasing cellular reactive oxygen species levels. Experiments with several blockers of cystathionine γ-lyase (CSE), the enzyme responsible for sulphide synthesis in the vasculature, demonstrated that propargylglycine (PAG, 1 mm) had little or no effect on the NPV caused by PGF2α or LY83583. Conversely, other CSE antagonists tested, aminooxyacetic acid (AOAA, 100 μm), β-cyanoalanine (BCA, 500 μm) and hydroxylamine (HA, 100 μm), altered the NPV to PGF2α (BCA increased, HA inhibited) and/or LY83583 (BCA increased, AOAA and HA inhibited). Preincubating IPAs in physiological saline solution (PSS) containing 1 mm cysteine increased the amplitude of the NPV to PGF2(α) by ∼50%, and had a similar effect on HPV elicited by hypoxic challenge with 0% O2 . The enhancement of both responses by cysteine was abolished by pretreatment with 1 mm PAG. Measurements carried out with an amperometric electrode demonstrated that incubation with 1 mm cysteine under anoxic conditions (to minimize sulphide oxidation) greatly potentiated the release of sulphide from pieces of rat liver and that this release was strongly antagonized by PAG, indicating that at this concentration PAG could enter cells intact and antagonize CSE. PAG at 1 mm had no effect on HPV recorded in control PSS, or in PSS supplemented with physiological concentrations of cysteine (10 μm), cystine (50 μm) and glutamate (100 μm) in order to prevent the possible depletion of intracellular

  9. Sensitivity and open-loop control of stochastic response in a noise amplifier flow: the backward-facing step

    CERN Document Server

    Boujo, Edouard

    2014-01-01

    The two-dimensional backward-facing step flow is a canonical example of noise amplifier flow: global linear stability analysis predicts that it is stable, but perturbations can undergo large amplification in space and time as a result of non-normal effects. This amplification potential is best captured by optimal transient growth analysis, optimal harmonic forcing, or the response to sustained noise. In view of reducing disturbance amplification in these globally stable open flows, a variational technique is proposed to evaluate the sensitivity of stochastic amplification to steady control. Existing sensitivity methods are extended in two ways to achieve a realistic representation of incoming noise: (i) perturbations are time-stochastic rather than time-harmonic, (ii) perturbations are localised at the inlet rather than distributed in space. This allows for the identification of regions where small-amplitude control is the most effective, without actually computing any controlled flows. In particular, passive...

  10. Multi-parameter trajectory sensitivity approach for location of series-connected controllers to enhance power system transient stability

    Energy Technology Data Exchange (ETDEWEB)

    Zamora-Cardenas, A.; Fuerte-Esquivel, Claudio R. [Universidad Michoacana de San Nicolas de Hidalgo, Faculty of Electrical Enginering, Morelia, Michoacan (Mexico)

    2010-09-15

    Determining suitable locations of series-connected controllers is a practical problem when it is necessary to install them in modern power systems. The aim of this paper is to find the best location of series controllers in order to reduce the proximity to instability of a current operating point of a power system, from a transient stability viewpoint. In order to achieve this goal, a general approach has been developed based on an index of proximity to instability and trajectory sensitivity analysis. An efficient way to carry out multi-parameter sensitivities is formulated analytically and solved simultaneously with the set of differential-algebraic equations representing power system's dynamics within a single-frame of reference. Simulations are performed on 9-bus and 39-bus benchmark power systems for illustration purposes. Results show that the proposed approach provides the most effective location of series-connected controllers to improve the power system's transient behavior. (author)

  11. The metabolomic profile of umbilical cord blood in neonatal hypoxic ischaemic encephalopathy.

    Directory of Open Access Journals (Sweden)

    Brian H Walsh

    Full Text Available BACKGROUND: Hypoxic ischaemic encephalopathy (HIE in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE. METHODS AND FINDINGS: The injury severity was defined using both the modified Sarnat score and continuous multichannel electroencephalogram. Using these classification systems, our population was divided into those with confirmed HIE (n = 31, asphyxiated infants without encephalopathy (n = 40 and matched controls (n = 71. All had umbilical cord blood drawn and biobanked at -80 °C within 3 hours of delivery. A combined direct injection and LC-MS/MS assay (AbsolutIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria was used for the metabolomic analyses of the samples. Targeted metabolomic analysis showed a significant alteration between study groups in 29 metabolites from 3 distinct classes (Amino Acids, Acylcarnitines, and Glycerophospholipids. 9 of these metabolites were only significantly altered between neonates with Hypoxic ischaemic encephalopathy and matched controls, while 14 were significantly altered in both study groups. Multivariate Discriminant Analysis models developed showed clear multifactorial metabolite associations with both asphyxia and HIE. A logistic regression model using 5 metabolites clearly delineates severity of asphyxia and classifies HIE infants with AUC = 0.92. These data describe wide-spread disruption to not only energy pathways, but also nitrogen and lipid metabolism in both asphyxia and HIE. CONCLUSION: This study shows that a multi-platform targeted approach to

  12. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

    Directory of Open Access Journals (Sweden)

    Todd Bradley

    2016-10-01

    Full Text Available Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1 viruses or rare cases of vaccine-matched neutralization-resistant (tier-2 viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.

  13. Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats.

    Science.gov (United States)

    Roth, Steven; Dreixler, John C; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R; Boddapoti, Venkat; Xue, Lai; Lesniak, Maciej S

    2016-06-01

    We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Eyes injected with hypoxic BMSC-conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect.

  14. [Hypoxic brain injuries notified to the Danish Patient Insurance Association during 1992-2004. Secondary publication

    DEFF Research Database (Denmark)

    Bock, J.; Christoffersen, J.K.; Hedegaard, M.

    2008-01-01

    We investigated the files of the Danish Patient Insurance Association for newborns suffering from hypoxic brain injuries. From 1992 to 2004, a total of 127 approved claims concerning peripartum hypoxic injury were registered. Thirty-eight newborns died and the majority of the 89 surviving children...

  15. microRNA regulation of the embryonic hypoxic response in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Kagias, Konstantinos; Pocock, Roger

    2015-01-01

    Layered strategies to combat hypoxia provide flexibility in dynamic oxygen environments. Here we show that multiple miRNAs are required for hypoxic survival responses during C. elegans embryogenesis. Certain miRNAs promote while others antagonize the hypoxic survival response. We found that expre...

  16. Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status.

    NARCIS (Netherlands)

    Sprong, D.; Janssen, H.L.K.; Vens, C.; Begg, A.C.

    2006-01-01

    PURPOSE: To determine the role of DNA repair in hypoxic radioresistance. METHODS AND MATERIALS: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic (&

  17. Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice.

    Science.gov (United States)

    Wakai, Takuma; Narasimhan, Purnima; Sakata, Hiroyuki; Wang, Eric; Yoshioka, Hideyuki; Kinouchi, Hiroyuki; Chan, Pak H

    2016-12-01

    Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.

  18. [Hypoxic brain injuries notified to the Danish Patient Insurance Association during 1992-2004. Secondary publication

    DEFF Research Database (Denmark)

    Bock, J.; Christoffersen, J.K.; Hedegaard, M.;

    2008-01-01

    We investigated the files of the Danish Patient Insurance Association for newborns suffering from hypoxic brain injuries. From 1992 to 2004, a total of 127 approved claims concerning peripartum hypoxic injury were registered. Thirty-eight newborns died and the majority of the 89 surviving childre...

  19. Early Predictors of Neurodevelopmental Adverse Outcome in Term Infants with Postasphyxial Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Khaled Abdulqawi

    2011-11-01

    Full Text Available Background: Neonatal brain injury due to intrapartum asphyxia is an important cause of cerebral palsy, mental retardation, and epilepsy. In developing countries, the incidence of post asphyxial neurological damage is particularly high. Despite advances in perinatal care over the past three decades, the incidence of cerebral palsy attributed to birth asphyxia has not changed.Objectives: To predict the outcome of postasphyxial hypoxic ischemic encephalopathy early in the neonatal period, for proper counseling of the parents, to get benefit in clinical practice and to select patients who will benefit from recent management strategies.Study Design: This study was conducted on 63 asphyxiated full term newborn infants who developed Hypoxic-Ischemic Encephalopathy (HIE admitted at Neonatal Intensive Care Unit of Al-Jedaany Hospital, Jeddah, Kingdom Saudi Arabia in the period from May 2006 to January 2008. They were classified according to Sarnat and Sarrnat staging of HIE into the following: 16 with stage I, HIE (Group I, 19 with stage II, HIE (Group II and 20 with stage III, HIE (Group III. Twenty full term healthy newborn infants, age and weight-matched, were served as a control. All infants were subjected to the following tests: cord blood gases at birth, and Urine sample for testing urinary lactate / creatinine ratio. Also a real-time cranial ultrasonography was done for infants who had HIE. Follow up of the cases was done by the followings: A neurodevelopmental clinical evaluation every three months till the age of one year of life was done for the cases and control infants. An Electroencephalogram (EEG and auditory brainstem evoked response (ABR were done at the age of three months and a second ABR at the age of six months for cases with abnormal previous ABR. Results: Group III (stage III, HIE has significantly increased initial, maximum and day 7 HIE scores (16.4 ± 3.1, 18.15 ± 2.79 and 13 ± 5.79 respectively compared with group I&II. Also

  20. Induction of cancer cell death by proton beam in tumor hypoxic region

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. M.; Heo, T. R.; Lee, K. B.; Jang, K. H.; Kim, H. N.; Lee, S. H.; Jeong, M. H. [Kyungpook National University, Daegu (Korea, Republic of)

    2008-04-15

    Proton beam has been applied to treat various tumor patients in clinical studies. However, it is still undefined whether proton radiation can inhibit the blood vessel formation and induce the cell death in vascular endothelial cells in growing organs. The aim of this study are first, to develop an optimal animal model for the observation of blood vessel development with low dose of proton beam and second, to investigate the effect of low dose proton beam on the inhibition of blood vessel formation induced by hypoxic conditions. In this study, flk1-GFP transgenic zebrafish embryos were used to directly visualize and determine the inhibition of blood vessels by low dose (1, 2, 5 Gy) of proton beam with spread out Bragg peak (SOBP). And we observed cell death by acridine orange staining at 96 hours post fertilization (hpf) stage of embryos after proton irradiation. We also compared the effects of proton beam with those of gamma-ray. An antioxidant, N-acetyl cystein (NAC) was used to investigate whether reactive oxygen species (ROS) were involved in the cell deaths induced by proton irradiation. Irradiated flk-1-GFP transgenic embryos with proton beam irradiation (35 MeV, spread out Bragg peak, SOBP) demonstrated a marked inhibition of embryonic growth and an altered fluorescent blood vessel development in the trunk region. When the cells with DNA damage in the irradiated zebrafish were stained with acridine orange, green fluorescent cell death spots were increased in trunk regions compared to non-irradiated control embryos. Proton beam also significantly increased the cell death rate in human umbilical vein endothelial cells (HUVEC), but pretreatment of N-acetyl cystein (NAC), an antioxidant, recovered the proton-induced cell death rate (p<0.01). Moreover, pretreatment of NAC abrogated the effect of proton beam on the inhibition of trunk vessel development and malformation of trunk truncation. From this study, we found that proton radiation therapy can inhibit the

  1. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  2. Regional hypoxic pulmonary vasoconstriction in dogs with asymptomatic dirofilariasis.

    Science.gov (United States)

    Chapleau, M W; Fish, R E; Levitzky, M G

    1985-06-01

    The pulmonary hemodynamic response to unilateral alveolar hypoxia was investigated in pentobarbital-anesthetized dogs with mild heartworm (HW) disease and in dogs free of HW (HWF). Left lung nitrogen ventilation in HWF dogs resulted in a decrease in the fraction of the cardiac output (QT) perfusing the left lung (QL) from 0.37 +/- 0.03 (SEM) to 0.20 +/- 0.02 (P less than 0.01). In contrast, dogs with mild HW disease did not develop a significant decrease in QL/QT which decreased from 0.38 +/- 0.02 to 0.33 +/- 0.02. This attenuated pulmonary vascular response to regional alveolar hypoxia in dogs with HW disease was associated with a normal pulmonary arterial pressure (14.8 +/- 1.5 mm of Hg) that was not different from that seen in HWF dogs (15.8 +/- 1.7 mm of Hg). These results indicate that mild HW disease interferes with the ability of hypoxic pulmonary vasoconstriction to redistribute pulmonary blood flow away from hypoxic regions of the lung.

  3. Concordance between hypoxic challenge testing and predictive equations for hypoxic flight assessment in chronic obstructive pulmonary disease patients prior to air travel

    Directory of Open Access Journals (Sweden)

    Mohie Aldeen Abd Alzaher Khalifa

    2016-10-01

    Conclusions: The present study supports on-HCT as a reliable, on-invasive and continuous methods determining the requirement for in-flight O2 are relatively constant. Predictive equations considerably overestimate the need for in-flight O2 compared to hypoxic inhalation test. Predictive equations are cheap, readily available methods of flight assessment, but this study shows poor agreement between their predictions and the measured individual hypoxic responses during HCT.

  4. Improved photovoltaic response of nanocrystalline CdS-sensitized solar cells through interface control.

    Science.gov (United States)

    Hwang, Jae-Yeol; Lee, Sang-A; Lee, Yong Hui; Seok, Sang-Il

    2010-05-01

    Nanocrystalline CdS-sensitized solar cells (CdS-SSCs) based on mesoporous TiO(2) were fabricated by the spray pyrolysis deposition method. The energy conversion efficiency of these cells was drastically increased (156%) by modifying the junction structure through post-treatment that included soaking in a dilute TiCl(4) aqueous solution and subsequent thermal annealing. We propose that the post-treatment is responsible for an increased number of interconnections between TiO(2) and CdS, as well as surface passivation of the CdS sensitizer. The increase in the cell efficiency is attributed to the improved charge carrier transport, suppression of photoelectron recombination with holes both in the same sensitizer particle and in nearby ones, and suppression of photoelectron capture by the electrolyte.

  5. Orbital Topology Controlling Charge Injection in Quantum-Dot-Sensitized Solar Cells.

    Science.gov (United States)

    Hansen, Thorsten; Žídek, Karel; Zheng, Kaibo; Abdellah, Mohamed; Chábera, Pavel; Persson, Petter; Pullerits, Tõnu

    2014-04-03

    Quantum-dot-sensitized solar cells are emerging as a promising development of dye-sensitized solar cells, where photostable semiconductor quantum dots replace molecular dyes. Upon photoexcitation of a quantum dot, an electron is transferred to a high-band-gap metal oxide. Swift electron transfer is crucial to ensure a high overall efficiency of the solar cell. Using femtosecond time-resolved spectroscopy, we find the rate of electron transfer to be surprisingly sensitive to the chemical structure of the linker molecules that attach the quantum dots to the metal oxide. A rectangular barrier model is unable to capture the observed variation. Applying bridge-mediated electron-transfer theory, we find that the electron-transfer rates depend on the topology of the frontier orbital of the molecular linker. This promises the capability of fine tuning the electron-transfer rates by rational design of the linker molecules.

  6. Effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Jian-Ning Zhang

    2016-01-01

    Objective:To analyze the effect of NGF combined with citicoline + cerebroprotein hydrolysate on neurobehavioral development and serum indexes in neonatal hypoxic ischemic encephalopathy.Methods: A total of 68 children with neonatal hypoxic ischemic encephalopathy (HIE) were randomly divided into observation group and control group, control group received supportive treatment + NGF combined with citicoline therapy, observation group received supportive treatment + NGF combined with citicoline and cerebroprotein hydrolysate treatment, and then differences in the levels of neurobehavioral development, creatine kinase and brain band, illness-related indexes,etc. were compared between two groups. Results: Serum nerve indexes NSE and S100B levels as well as myocardial enzyme spectrum-related parameters CK, CK-BB and CK-MB levels of observation group after treatment were lower than those of control group (P<0.05); serum MBP, ET-1, NO and CO levels were lower than those of control group, and FN level was higher than that of control group (P<0.05). Conclusions: NGF combined with citicoline + cerebroprotein hydrolysate therapy for children with HIE can reduce brain tissue damage and optimize physical status, and it is of positive clinical significance.

  7. Strain response of stretchable micro-electrodes: Controlling sensitivity with serpentine designs and encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Gutruf, Philipp; Walia, Sumeet; Nur Ali, Md; Sriram, Sharath, E-mail: sharath.sriram@gmail.com, E-mail: madhu.bhaskaran@gmail.com; Bhaskaran, Madhu, E-mail: sharath.sriram@gmail.com, E-mail: madhu.bhaskaran@gmail.com [Functional Materials and Microsystems Research Group, School of Electrical and Computer Engineering, RMIT University, GPO Box 2476, Melbourne, Victoria (Australia)

    2014-01-13

    The functionality of flexible electronics relies on stable performance of thin film micro-electrodes. This letter investigates the behavior of gold thin films on polyimide, a prevalent combination in flexible devices. The dynamic behavior of gold micro-electrodes has been studied by subjecting them to stress while monitoring their resistance in situ. The shape of the electrodes was systematically varied to examine resistive strain sensitivity, while an additional encapsulation was applied to characterize multilayer behavior. The realized designs show remarkable tolerance to repetitive strain, demonstrating that curvature and encapsulation are excellent approaches for minimizing resistive strain sensitivity to enable durable flexible electronics.

  8. Clinical analysis of the early comprehensive intervention on hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Xu-E Li; Yi-MinDu; Yan-JuGuo; Zhi-QingWu; Su-GeHao

    2015-01-01

    Objective:To explore the clinical efficacy of the early comprehensive intervention on hypoxic ischemic encephalopathy (HIE).Methods:HIE children who were admitted in our department from March, 2014 to May, 2015 were included in the study and randomized into the observation group and the control group. The patients in the control group were given routine fluid infusion, electrolyte disturbance correcting, blood sugar maintaining, convulsion controlling, intracranial pressure reducing, hormone, mannitol, vitamins, infection preventing, and other treatments. Based on the treatments given in the control group, the patients in the observation group were given the comprehensive intervention. After treatment, the serum related indicators, NBNA, and DQ in the two groups were observed.Results:The levels of serum AST, LDH, CK, and CK-MB in the observation group were significantly lower than those in the control group (P0.05). NBNA score in the observation group was significantly superior to that in the control group (P<0.05). DQ values at 3, 6, 12, 18, and 24 months in the observation group were significantly higher than those in the control group (P<0.05).Conclusions:Early comprehensive intervention on HIE patients can effectively reduce the serum cardiac enzyme levels, increase the therapeutic effect, improve the intelligence and motor development levels and DQ in order to enhance the living qualities.

  9. Efficiency enhancement in solid state dye sensitized solar cells by including inverse opals with controlled layer thicknesses

    Science.gov (United States)

    Zheng, Hanbin; Shah, Said Karim; Abbas, Mamatimin; Ly, Isabelle; Rivera, Thomas; Almeida, Rui M.; Hirsch, Lionel; Toupance, Thierry; Ravaine, Serge

    2016-09-01

    The photoconversion efficiency of dye sensitized solar cells can be enhanced by the incorporation of light management nanostructures such as photonic crystals. Here, we present a facile route to incorporate titania inverse opals into solid state dye sensitized solar cells and report photoconversion efficiency enhancements of up to 56% compared with a model system without the inverse opal. Our approach is based on the precise design of titania inverse opals with a predetermined thickness that can be controlled at the individual layer level. By choosing an inverse opal exhibiting a photonic bandgap which overlaps the absorption bands of the dye, our results show that there is an optimal thickness of the inverse opal structure for maximum efficiency enhancement of the cell. This is the first experimental proof that the thickness of a titania inverse opal plays a pivotal role in cell efficiency enhancement in solid state dye sensitized solar cells.

  10. Reward sensitivity, attentional bias, and executive control in early adolescent alcohol use

    NARCIS (Netherlands)

    M.E. van Hemel-Ruiter; P.J. de Jong; B.D. Ostafin; R.W. Wiers

    2014-01-01

    This study examined whether attentional bias for alcohol stimuli was associated with alcohol use in young adolescents, and whether the frequently demonstrated relationship between reward sensitivity and adolescent alcohol use would be partly mediated by attentional bias for alcohol cues. In addition

  11. Reward sensitivity, attentional bias, and executive control in early adolescent alcohol use

    NARCIS (Netherlands)

    van Hemel-Ruiter, Madelon E.; de Jong, Peter J.; Ostafin, Brian D.; Wiers, Reinout W.

    2015-01-01

    This study examined whether attentional bias for alcohol stimuli was associated with alcohol use in young adolescents, and whether the frequently demonstrated relationship between reward sensitivity and adolescent alcohol use would be partly mediated by attentional bias for alcohol cues. In addition

  12. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    S.A.W. Bouwense (Stefan); S.S. Olesen (Søren); A.M. Drewes (Asbjørn); J.-W. Poley (Jan-Werner); H. van Goor (Harry); O.H.G. Wilder-Smith (Oliver)

    2012-01-01

    textabstractBackground: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate

  13. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial.

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Olesen, S.S.; Drewes, A.M.; Poley, J.W.; Goor, H. van; Wilder-Smith, O.H.G.

    2012-01-01

    BACKGROUND: Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect

  14. Reward sensitivity, attentional bias, and executive control in early adolescent alcohol use

    NARCIS (Netherlands)

    van Hemel-Ruiter, M.E.; de Jong, P.J.; Ostafin, B.D.; Wiers, R.W.

    2015-01-01

    This study examined whether attentional bias for alcohol stimuli was associated with alcohol use in young adolescents, and whether the frequently demonstrated relationship between reward sensitivity and adolescent alcohol use would be partly mediated by attentional bias for alcohol cues. In

  15. Reward sensitivity, attentional bias, and executive control in early adolescent alcohol use

    NARCIS (Netherlands)

    van Hemel-Ruiter, Madelon E.; de Jong, Peter J.; Ostafin, Brian D.; Wiers, Reinout W.

    This study examined whether attentional bias for alcohol stimuli was associated with alcohol use in young adolescents, and whether the frequently demonstrated relationship between reward sensitivity and adolescent alcohol use would be partly mediated by attentional bias for alcohol cues. In

  16. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity

    NARCIS (Netherlands)

    Stienstra, R.; Joosten, L.A.; Koenen, T.; Tits, van B.; Diepen, van J.A.; Berg, van den S.A.A.; Rensen, P.C.; Voshol, P.J.; Fantuzzi, G.; Hijmans, A.; Kersten, A.H.; Müller, M.R.; Berg, van den W.B.; Rooijen, van N.; Wabitsch, M.; Kullberg, B.J.; Meer, van der J.W.; Kanneganti, T.; Tack, C.J.; Netea, M.G.

    2010-01-01

    Obesity-induced inflammation originating from expanding adipose tissue interferes with insulin sensitivity. Important metabolic effects have been recently attributed to IL-1ß and IL-18, two members of the IL-1 family of cytokines. Processing of IL-1ß and IL-18 requires cleavage by caspase-1, a

  17. 4-nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.

    Science.gov (United States)

    Wang, Li-E; Li, Chunying; Xiong, Ping; Gershenwald, Jeffrey E; Prieto, Victor G; Duvic, Madeleine; Lee, Jeffrey E; Grimm, Elizabeth A; Hsu, Tao C; Wei, Qingyi

    2016-04-01

    Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case-control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 μmol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P=0.004) and was associated with an increased risk for CM (adjusted odds ratio=1.78, 95% confidence interval: 1.12-2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (P(trend)=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (P(interaction)=0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromotid breaks.

  18. Control of channel doping concentration for enhancing the sensitivity of 'top-down' fabricated Si nanochannel FET biosensors

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Woo; Ahn, Chang-Geun; Yang, Jong-Heon; Baek, In-Bok; Ah, Chil Seong; Kim, Ansoon; Kim, Tae-Youb; Sung, Gun Yong, E-mail: chanwoo@etri.re.k, E-mail: gysung@etri.re.k [Biosensor Research Team, Electronics and Telecommunications Research Institute (ETRI), Daejeon 305-700 (Korea, Republic of)

    2009-11-25

    The sensitivity of 'top-down' fabricated Si nanochannel field effect transistor (FET) biosensors has been analyzed quantitatively, as a function of the channel width and doping concentration. We have fabricated 130-, 150-, and 220 nm-wide Si FET channels with 40 nm-thick p-type silicon-on-insulator (SOI) layers doped at 8 x 10{sup 17} and 2 x 10{sup 18} cm{sup -3}, and characterized their sensitivity in response to the variation of surface charges as hydrogen ion sensors within buffer solutions of various pH levels. Within the range of channel width and doping concentration investigated, the pH sensitivity of Si channels is enhanced much more effectively by decreasing the doping concentration than by reducing the channel width, which suggests a practical strategy for achieving high sensitivity with less effort than to reduce the channel width. Similar behavior has also been confirmed in the immunodetection of prostate specific antigen (PSA). Combined with excellent reproducibility and uniformity of the channel structure, high controllability of the doping concentration can make the 'top-down' fabrication a very useful approach for the massive fabrication of high-sensitivity sensor platforms in a cost-effective way.

  19. Effect of hypoxic acclimation on anoxia tolerance in Vitis roots: response of metabolic activity and K+ fluxes.

    Science.gov (United States)

    Mugnai, Sergio; Marras, Anna Maria; Mancuso, Stefano

    2011-06-01

    The effect of a hypoxic pre-treatment (HPT) on improving tolerance to prolonged anoxia conditions in two contrasting Vitis species (V. riparia, anoxia tolerant; V. rupestris, anoxia sensitive) was evaluated. The energy economy of root cells was studied by measuring heat production, the activity of pyruvate decarboxylase (PDC) and alcohol dehdrogenase (ADH), ethanol and ATP production, and K(+) fluxes. The results showed that HPT is an effective tool in order to maintain a sustainable metabolic performance in both the species under anoxia conditions, especially in sensitive species such as V. rupestris. Our results showed that the improved tolerance was mainly driven by: (i) an enhanced activity of key enzymes in alcohol fermentation (ADC and PDC); (ii) the capability to maintain a higher level of respiration, evidenced by a lesser decrease in heat development and ATP production; and (iii) the maintenance of a better ion homeostasis (highlighted by measurement of K(+) fluxes) and K(+) channel functionality.

  20. Effects of hypercapnic-hypoxic training on respiratory muscle strength and front crawl stroke performance among elite swimmers

    OpenAIRE

    KARAULA, Dajana; HOMOLAK, Jan; Leko, Goran

    2016-01-01

    The aim of this resent study was to determine the effects of an 8-week hypercapnic-hypoxic (H-H or apnea) training program on respiratory muscles strength and 100 meter crawl swimming performance. The study was conducted on a sample of 26 Croatian elite swimmers (experimental group [EG] n=12, control group [CG]   n=14). Both groups were subjected to the same swimming training programs and training sessions on a treadmill. The experimental group was additionally subjected to hypercapnic-hypoxi...

  1. USING OXYGEN-CONSUMING THERMOSET PLASTICS TO GENERATE HYPOXIC CONDITIONS IN MICROFLUIDIC DEVICES FOR POTENTIAL CELL CULTURE APPLICATIONS

    DEFF Research Database (Denmark)

    Sticker, Drago; Rothbauer, Mario; Ehgartner, Josef

    2017-01-01

    The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell- and organ......-on-chip applications. Using a thermoset polymeric material (OSTEMERTM), which effectively scavenges dissolved oxygen (DO), microfluidic devices have been fabricated where oxygen was rapidly depleted from the microfluidic chamber. It is shown that hypoxic and anaerobic conditions can be generated through the inherent...

  2. Determination of sensitivity for in-process control of cable product insulation

    Science.gov (United States)

    Redko, V. V.; Starikova, N. S.; Redko, L. A.; Vavilova, G. V.

    2015-04-01

    This article presents current methods of cable insulation control. The new method which allows to improve reliability of cable insulation control was offered. The cable model with several types of defects was developed by using Comsol Myltiphysics software. Minimal sizes of defects which can be detected by using given in-process control method.

  3. Sensitivity analysis of an optimal control problem in greenhouse climate management.

    NARCIS (Netherlands)

    Henten, van E.J.

    2003-01-01

    Optimal control systems are based on a performance measure to be optimised and a model description of the dynamic process to be controlled. When on-line implementation is considered, the performance of optimally controlled processes will depend on the accuracy of the model description used. Sensitiv

  4. The effect of normobaric hypoxic confinement on metabolism, gut hormones and body composition

    Directory of Open Access Journals (Sweden)

    Igor B. Mekjavic

    2016-06-01

    Full Text Available To assess the effect of normobaric hypoxia on metabolism, gut hormones and body composition, eleven normal weight, aerobically trained ( O2peak: 60.6±9.5 ml·kg-1·min-1 men (73.0±7.7 kg; 23.7±4.0 yrs, BMI 22.2±2.4 kg·m-2 were confined to a normobaric (altitude⋍940m normoxic (NORMOXIA; PIO2⋍133.2 mmHg or normobaric hypoxic (HYPOXIA; PIO was reduced from 105.6 to 97.7 mmHg over 10 days environment for 10 days in a randomized cross-over design. The wash-out period between confinements was 3 weeks. During each 10-day period, subjects avoided strenuous physical activity and were under continuous nutritional control. Before, and at the end of each exposure, subjects completed a meal tolerance test, during which blood glucose, insulin, GLP-1, ghrelin, peptide-YY, adrenaline, noradrenaline, leptin, and gastro-intestinal blood flow and appetite sensations were measured. There was no significant change in body weight in either of the confinements (NORMOXIA: -0.7±0.2 kg; HYPOXIA: -0.9±0.2 kg, but a significant increase in fat mass in NORMOXIA (0.23±0.45 kg, but not in HYPOXIA (0.08±0.08 kg. HYPOXIA confinement increased fasting noradrenaline and decreased energy intake, the latter most likely associated with increased fasting leptin. The majority of all other measured variables/responses were similar in NORMOXIA and HYPOXIA. To conclude, normobaric hypoxic confinement without exercise training results in negative energy balance due to primarily reduced energy intake.

  5. Mussel-inspired polydopamine coated mesoporous silica nanoparticles as pH-sensitive nanocarriers for controlled release.

    Science.gov (United States)

    Zheng, Qishan; Lin, Tianran; Wu, Hanyin; Guo, Liangqia; Ye, Peirong; Hao, Yanli; Guo, Qingquan; Jiang, Jinzhi; Fu, Fengfu; Chen, Guonan

    2014-03-10

    A novel pH-sensitive controlled release system is proposed by using mussel-inspired polydopamine (PDA) coated mesoporous silica nanoparticles (MSNs) as nanocarriers. MSNs with a large pore diameter are synthesized by using 1,3,5-trimethylbenzene as a pore-expanding agent and are modified with a PDA coating by virtue of oxidative self-polymerization of dopamine in neutral pH. PDA coated MSNs are characterized by FTIR, TEM, N₂ adsorption and XPS techniques. The PDA coating can work as pH-sensitive gatekeepers to control the release of drug molecules from MSNs in response to the pH-stimulus. Doxorubicin (DOX, an anticancer drug) can be released in the acid media and blocked in the neutral media. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Lijun Yang; Hong Cui; Ting Cao

    2014-01-01

    Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair. miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin-formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups:control group;oxygen-glucose deprivation group (treatment with 8% O2+ 92%N2 and sugar-free medium for 60 minutes);transfection control group (after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid) and miRNA-9 transfection group (after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid). From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden-drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.

  7. OPTIMIZATION OF THE TEMPERATURE CONTROL SCHEME FOR ROLLER COMPACTED CONCRETE DAMS BASED ON FINITE ELEMENT AND SENSITIVITY ANALYSIS METHODS

    Directory of Open Access Journals (Sweden)

    Huawei Zhou

    2016-10-01

    Full Text Available Achieving an effective combination of various temperature control measures is critical for temperature control and crack prevention of concrete dams. This paper presents a procedure for optimizing the temperature control scheme of roller compacted concrete (RCC dams that couples the finite element method (FEM with a sensitivity analysis method. In this study, seven temperature control schemes are defined according to variations in three temperature control measures: concrete placement temperature, water-pipe cooling time, and thermal insulation layer thickness. FEM is employed to simulate the equivalent temperature field and temperature stress field obtained under each of the seven designed temperature control schemes for a typical overflow dam monolith based on the actual characteristics of a RCC dam located in southwestern China. A sensitivity analysis is subsequently conducted to investigate the degree of influence each of the three temperature control measures has on the temperature field and temperature tensile stress field of the dam. Results show that the placement temperature has a substantial influence on the maximum temperature and tensile stress of the dam, and that the placement temperature cannot exceed 15 °C. The water-pipe cooling time and thermal insulation layer thickness have little influence on the maximum temperature, but both demonstrate a substantial influence on the maximum tensile stress of the dam. The thermal insulation thickness is significant for reducing the probability of cracking as a result of high thermal stress, and the maximum tensile stress can be controlled under the specification limit with a thermal insulation layer thickness of 10 cm. Finally, an optimized temperature control scheme for crack prevention is obtained based on the analysis results.

  8. The driver vigilance telemetric control system (DVTCS): investigating sensitivity to experimentally induced sleep loss and fatigue.

    Science.gov (United States)

    Dorrian, Jillian; Lamond, Nicole; Kozuchowski, Karolina; Dawson, Drew

    2008-11-01

    Vigilance technologies are used in the Australian rail industry to address the risks associated with driver sleepiness and fatigue. The aim of this study was to investigate whether a new device, designed to detect lowered states of arousal using electrodermal activity (EDA), would be sensitive to experimentally induced sleepiness and fatigue. Fifteen individuals (7 of them female, 9 male; 18-32 years of age) spent 3 consecutive days in the laboratory, which included 1 night of sustained wakefulness (28 h). The participants completed a 10-min psychomotor vigilance task (PVT) and fatigue and sleepiness ratings every 2 h, and a 30-min driving simulator every 4 h. As was expected, simulated driving, PVT, and subjective ratings indicated increasing levels of sleepiness and fatigue during sustained wakefulness. The EDA device output did not coincide with these findings. The results indicated that the EDA indicator was not sensitive to increased sleepiness and fatigue at the levels produced in the present study.

  9. Highly stretchable and wearable graphene strain sensors with controllable sensitivity for human motion monitoring.

    Science.gov (United States)

    Park, Jung Jin; Hyun, Woo Jin; Mun, Sung Cik; Park, Yong Tae; Park, O Ok

    2015-03-25

    Because of their outstanding electrical and mechanical properties, graphene strain sensors have attracted extensive attention for electronic applications in virtual reality, robotics, medical diagnostics, and healthcare. Although several strain sensors based on graphene have been reported, the stretchability and sensitivity of these sensors remain limited, and also there is a pressing need to develop a practical fabrication process. This paper reports the fabrication and characterization of new types of graphene strain sensors based on stretchable yarns. Highly stretchable, sensitive, and wearable sensors are realized by a layer-by-layer assembly method that is simple, low-cost, scalable, and solution-processable. Because of the yarn structures, these sensors exhibit high stretchability (up to 150%) and versatility, and can detect both large- and small-scale human motions. For this study, wearable electronics are fabricated with implanted sensors that can monitor diverse human motions, including joint movement, phonation, swallowing, and breathing.

  10. Sensitivity of measured steam oxidation kinetics to atmospheric control and impurities

    Science.gov (United States)

    Sooby Wood, E.; Terrani, K. A.; Nelson, A. T.

    2016-08-01

    The most direct means of improving the ability of water cooled reactors to withstand excessive cladding oxidation during a loss of coolant accident is to either modify or replace zirconium cladding. It is important to understand what level of agreement is to be expected as a function of systematic differences in steam oxidation testing techniques and instrumentation among testing facilities. The present study was designed to assess the sensitivities of some of the current and proposed reactor cladding materials. Steam oxidation sensitivity of Zircaloy-2, FeCrAl and Mo to O2 impurities in steam were examined. It was shown that the effect of O2 impurities is negligible for the two former materials while significant in the case of Mo.

  11. Probe frequency- and field intensity-sensitive coherent control effects in an EIT-based periodic layered medium

    Institute of Scientific and Technical Information of China (English)

    Teh-Chau Liau; Jin-Jei Wu; Jianqi Shen; Tzong-Jer Yang

    2012-01-01

    A periodic layered medium,with unit cells consisting of a dielectric and an electromagnetically-induced transparency (EIT)-based atomic vapor,is designed for light propagation manipulation. Considering that a destructive quantum interference relevant to a two-photon resonance emerges in EIT-based atoms interacting with both control and probe fields,an EIT-based periodic layered medium exhibits a flexible frequency-sensitive optical response,where a very small variation in the probe frequency can lead to a drastic variation in reflectance and transmittance.The present EIT-based periodic layered structure can result in controllable optical processes that depend sensitively on the external control field.The tunable and sensitive optical response induced by the quantum interference of a multi-level atomic system can be applied in the fabrication of new photonic and quantum optical devices.This material will also open a good perspective for the application of such designs in several new fields,including photonic microcircuits or integrated optical circuits.

  12. Controlling the Electrostatic Discharge Ignition Sensitivity of Composite Energetic Materials Using Carbon Nanotube Additives

    Science.gov (United States)

    2014-08-10

    ignition mechanismwas joule heating of the Al core as opposed to dielectric heating of the alumina shell. The ESD ignition sensitivity of aluminum...density gradients. A Nichrome resistive heating wire is placed within the tube with a pinched center that acts as a point heat source that is in...containing no CNT and the samples with 3.08, and 3.8 vol.% CNT were tested for flame speeds to determine CNT effect on resistive wire ignition and

  13. Sensitivity of grassland productivity to aridity controlled by stomatal and xylem regulation

    Science.gov (United States)

    Konings, A. G.; Williams, A. P.; Gentine, P.

    2017-03-01

    The terrestrial water and carbon cycles are coupled through plant regulation of stomatal closure. Both soil moisture and vapour pressure deficit--the amount of moisture in the air relative to its potential maximum--can govern stomatal closure, which reduces plant carbon uptake. However, plants vary in the degree to which they regulate their stomata--and in association, xylem conductance--in response to increasing aridity: isohydric plants exert tight regulation of stomata and the water content of the plant, whereas anisohydric plants do not. Here we use remote-sensing data sets of anisohydricity and vegetation greenness to show that productivity in United States grasslands--especially anisohydric ones--is far more sensitive to variations in vapour pressure deficit than to variations in precipitation. Anisohydric ecosystem productivity is over three times more sensitive to vapour pressure deficit than isohydric ecosystem productivity. The precipitation sensitivity of summer productivity increases with anisohydricity only for the most anisohydric ecosystems. We conclude that increases in vapour pressure deficit rather than changes in precipitation--both of which are expected impacts of climate change--will be a dominant influence on future grassland productivity.

  14. Insulin sensitivity affects propensity to obesity in an ethnic-specific manner: results from two controlled weight loss intervention studies

    Directory of Open Access Journals (Sweden)

    Gower Barbara A

    2013-01-01

    Full Text Available Abstract Background Risk for obesity differs with ethnicity/race and is associated with insulin sensitivity (SI, insulin responsiveness, and dietary glycemic load (GL. The objective of this study was to test the hypotheses that, 1 obesity-prone, normal weight, African-American (AA women would be more insulin sensitive than BMI-matched, never overweight AA women; 2 increased adiposity over time would be associated with greater baseline SI and higher dietary GL in AA but not European-American (EA women; and 3 increased adiposity over time would be predicted by SI in women with high but not low acute insulin response to glucose (AIRg. Methods Two controlled weight loss interventions were conducted involving overweight (BMI 25.0-29.9 kg/m2 premenopausal AA and EA women. The first included matching with normal-weight (BMI 2 controls following weight loss, and then comparing SI. The second included a 1-year follow-up of weight-reduced participants to identify predictors of change in %body fat. Main outcome measure in the first study was insulin sensitivity (SI as assessed with intravenous glucose tolerance test (IVGTT, and in the second study was change in %fat, as assessed with DXA, over one year. AIRg was assessed during IVGTT, and free-living diet was determined by food record. Results In the first study, formerly overweight AA women were 43% more insulin sensitive than BMI-matched never overweight AA (P I was positively associated with change in %fat over 1 year only in AA women (P P P = 0.086 for diet x SI interaction. In both studies, AA women had higher AIRg (P  Conclusions Formerly overweight (obesity-prone AA women were more insulin sensitive than never overweight AA women, a quality that may predispose to adiposity, particularly when combined with a high GL diet. This ethnicity/race-specific effect may be due to high insulin responsiveness among AA.

  15. Controllable preparation of TiO{sub 2} nanowire arrays on titanium mesh for flexible dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenwu; Lu, Hui; Zhang, Mei; Guo, Min, E-mail: guomin@ustb.edu.cn

    2015-08-30

    Graphical abstract: TiO{sub 2} nanowire arrays with controlled morphology and density have been synthesized on Ti mesh substrates by hydrothermal approach for flexible dye-sensitized solar cells which showed well photovoltaic efficiency of 3.42%. - Highlights: • Flexible titanium mesh was first used for hydrothermal preparation of TiO{sub 2} NWAs. • The formation mechanism of the TiO{sub 2} nanostructures was discussed. • The density, average diameter, and morphology of TiO{sub 2} NWAs can be controlled. • The effects of the sensitization temperature and time on the properties were studied. - Abstract: TiO{sub 2} nanowire arrays (NWAs) with an average diameter of 80 nm have been successfully synthesized on titanium (Ti) mesh substrates via hydrothermal method. The effects of preparing conditions such as concentration of NaOH solution, reaction time, and hydrothermal temperature on the growth of TiO{sub 2} nanoarrays and its related photovoltaic properties were systematically investigated by scanning electron microscopy, X-ray diffraction, and photovoltaic properties test. The growth mechanism of the Ti mesh-supported TiO{sub 2} nanostructures was discussed in detail. Moreover, a parametric study was performed to determine the optimized temperature and time of the dye sensitized process for the flexible dye-sensitized solar cell (DSSC). It is demonstrated that hydrothermal parameters had obvious influence on the morphology and growth density of the as-prepared TiO{sub 2} nanoarrays. In addition, the performance of the flexible DSSC depended strongly on the sensitization temperature and time. By utilizing Ti mesh-supported TiO{sub 2} NWAs (with a length of about 14 μm) as a photoanode, the flexible DSSC with a short circuit current density of 10.49 mA cm{sup −2}, an open-circuit voltage of 0.69 V, and an overall power conversion efficiency of 3.42% was achieved.

  16. Antisense suppression of cucumber (Cucumis sativus L.) sucrose synthase 3 (CsSUS3) reduces hypoxic stress tolerance.

    Science.gov (United States)

    Wang, Hongyun; Sui, Xiaolei; Guo, Jinju; Wang, Zhenyu; Cheng, Jintao; Ma, Si; Li, Xiang; Zhang, Zhenxian

    2014-03-01

    Sucrose synthase (SUS; EC 2.4.1.13) plays important roles in sugar metabolism and abiotic stress response. But the genes encoding SUS in cucumber (Cucumis sativus L.) have not been well studied. Here, we isolated four cucumber sucrose synthase genes (CsSUS). Among them, CsSUS3, which highly expressed in the roots, was chosen for further study. Immunolocalization and subcellular localization analysis indicated that CsSUS3 localized in the cytosol and the plasma membrane, and mainly existed in the companion cells of phloem in the roots. When suffering hypoxia stress from flooding, CsSUS3 expression and SUS activity in roots increased, especially in the lateral roots; moreover, the soluble SUS activity increased clearly, but the membrane fraction hardly changed. Compared with the wild-type cucumbers, the transgenic lines with antisense expression of CsSUS3 were more sensitive to flooding. After 6 d of flooding, the SUS activity, soluble sugar and uridine 5'-diphosphate glucose (UDPG) content and the ratio of ATP/ADP in the roots of transgenic plants were significantly lower than that in wild-type plants. Moreover, the transgenic lines grew more slowly with more yellow necrosis in the leaves. These findings suggested CsSUS3 participated in resisting hypoxic stress. Furthermore, the mechanism of CsSUS3 in resisting hypoxic stress was also discussed.

  17. Nitric oxide improves the hemodynamic performance of the hypoxic goldfish (Carassius auratus) heart

    DEFF Research Database (Denmark)

    Imbrogno, Sandra; Capria, C.; Tota, Bruno;

    2014-01-01

    nitric oxide (NO) under normoxic and hypoxic conditions. Cardiac performance was examined both under basal (constant preload and afterload) and loading conditions, i.e. preload-induced increases in stroke volume (SV) and hence cardiac output at constant afterload (the Frank–Starling response). Hypoxic...... to filling pressure increases; the maximum SV = 1.08 ± 0.09 mL/kg body mass was obtained at 0.4 kPa. Acute hypoxia increased this sensitivity, SV reaching the maximum value (1.45 ± 0.12 mL/kg body mass) at 0.25 kPa. NOS inhibition by L-NMMA reduced the Frank–Starling response under normoxia......, but was ineffective under acute hypoxia, where NO may come from nitrite reduction. In both conditions, sGC inhibition induced a reduction of the cardiac response to preload. Moreover, under acute hypoxia, NO scavenging significantly reduced the Frank–Starling response. The hypoxia-induced hemodynamic patterns were...

  18. Evolution of the Therapeutic Effects of Induced Local Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    B. Basiri

    2011-04-01

    Full Text Available Introduction & Objective: Hypoxic-ischemic encephalopathy is one of the most important causes of permanent damage to brain tissue that redound to mortality and/or late sequelae such as cerebral palsy or delayed neural development. 15-20 percent of Hypoxic-ischemic encephalopathy (HIE cases die during neonatal period and 25-30 percent of those who survive suffer from neural development problems such as cerebral palsy and mental retardation. Hypothermia or lowering temperature of brain or total body is a new and promising treatment. The present study was done to assess therapeutic effects of induced local hypothermia in hypoxic-ischemic encephalopathy (HIE among neonates admitted to Fatemieh and Beset hospitals of Hamadan city.Materials & Method: The present study was performed as a randomized clinical trial upon 36 neonates who had inclusion criteria to be imported into the study. In the first 6 hours after birth, the neonates were randomly classified into two 18 person groups. In the control group the neonates were managed with routine treatments consisted of preservative measures and anti-convulsive treatments, if necessary. In the case group the neonates received induced local hypothermia for 6 hours in addition to routine therapeutic managements. The data were analyzed using SPSS Version 13.Results: 72.7% of the neonates of the case and control groups were male. There was no significant difference between the case and control groups in sex, birth weight, gestational age and perinatal obstetric complications. The mean duration of admission was 7.72±4.23 days in the case group and 10.06±5.99 days in the control group with no significant difference between the two groups (P=0.199. The mean time of starting oral feeding was 3.44±3.11 days and 4.53±2.74 days in the control and case groups respectively and this difference was not statistically significant either (P=0.737.The mean time of regaining consciousness was 3.72±3.19 days in the case

  19. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-02-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5omicronC for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughtout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat.

  20. Hypoxic cell radiosensitization by moderate hyperthermia and glucose deprivation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H.; Kim, S.H.; Hahn, E.W.

    1983-02-01

    Cell culture studies were carried out to determine whether moderate hyperthermia reduces the oxygen enhancement ratio of cells under well-defined cultural conditions. Using asynchronously growing HeLa cells, the OER of cells with and without glucose was determined following exposure of cells to moderate hyperthermia, 40.5 degrees C for 1 hr, immediately after X irradiation. The OER of cells with 5 mM glucose was 3.2, whereas the OER of glucose-deprived cells was reduced to 2.0. The pH of the cell culture medium was kept at 7.4 throughout the experiments. The present finding may provide a clue toward further enhancing the radiosensitization of hypoxic cells by heat.

  1. The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning

    Science.gov (United States)

    Guo, Xiaowei; Jiang, Xupin; Ren, Xi; Sun, Huanbo; Zhang, Dongxia; Zhang, Qiong; Zhang, Jiaping; Huang, Yuesheng

    2015-01-01

    The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2, 6 hours) decreased the threshold voltage of galvanotaxis to keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing. PMID:25988491

  2. Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria.

    Science.gov (United States)

    Bettegowda, Chetan; Dang, Long H; Abrams, Ross; Huso, David L; Dillehay, Larry; Cheong, Ian; Agrawal, Nishant; Borzillary, Scott; McCaffery, J Michael; Watson, E Latice; Lin, Kuo-Shyan; Bunz, Fred; Baidoo, Kwamena; Pomper, Martin G; Kinzler, Kenneth W; Vogelstein, Bert; Zhou, Shibin

    2003-12-09

    The low level of oxygenation within tumors is a major cause of radiation treatment failures. We theorized that anaerobic bacteria that can selectively destroy the hypoxic regions of tumors would enhance the effects of radiation. To test this hypothesis, we used spores of Clostridium novyi-NT to treat transplanted tumors in mice. The bacteria were found to markedly improve the efficacy of radiotherapy in several of the mouse models tested. Enhancement was noted with external beam radiation derived from a Cs-137 source, systemic radioimmunotherapy with an I-131-conjugated monoclonal antibody, and a previously undescribed form of experimental brachytherapy using plaques loaded with I-125 seeds. C. novyi-NT spores added little toxicity to the radiotherapeutic regimens, and the combination resulted in long-term remissions in a significant fraction of animals.

  3. The hypoxia signaling pathway and hypoxic adaptation in fishes.

    Science.gov (United States)

    Xiao, Wuhan

    2015-02-01

    The hypoxia signaling pathway is an evolutionarily conserved cellular signaling pathway present in animals ranging from Caenorhabditis elegans to mammals. The pathway is crucial for oxygen homeostasis maintenance. Hypoxia-inducible factors (HIF-1α and HIF-2α) are master regulators in the hypoxia signaling pathway. Oxygen concentrations vary a lot in the aquatic environment. To deal with this, fishes have adapted and developed varying strategies for living in hypoxic conditions. Investigations into the strategies and mechanisms of hypoxia adaptation in fishes will allow us to understand fish speciation and breed hypoxia-tolerant fish species/strains. This review summarizes the process of the hypoxia signaling pathway and its regulation, as well as the mechanism of hypoxia adaptation in fishes.

  4. Sensitivity Analysis for the Optimal Design and Control of Advanced Guidance Systems

    Science.gov (United States)

    2007-06-01

    McMillan and R. Triggiani, Min-max game theory and algebraic Riccati equa- tions for boundary control problems with analytic semigroups , Part I: the stable...Riccati equations for boundary control prob- lems with analytic semigroups , Part II: The general case, Nonlinear Analysis, 22 (1994), pp. 431–465

  5. Overcoming Hypoxic-Resistance of Tumor Cells to TRAIL-Induced Apoptosis through Melatonin

    Directory of Open Access Journals (Sweden)

    You-Jin Lee

    2014-07-01

    Full Text Available A solid tumor is often exposed to hypoxic or anoxic conditions; thus, tumor cell responses to hypoxia are important for tumor progression as well as tumor therapy. Our previous studies indicated that tumor cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL-induced cell apoptosis under hypoxic conditions. Melatonin inhibits cell proliferation in many cancer types and induces apoptosis in some particular cancer types. Here, we examined the effects of melatonin on hypoxic resistant cells against TRAIL-induced apoptosis and the possible mechanisms of melatonin in the hypoxic response. Melatonin treatment increased TRAIL-induced A549 cell death under hypoxic conditions, although hypoxia inhibited TRAIL-mediated cell apoptosis. In a mechanistic study, hypoxia inducible factor-1α and prolyl-hydroxylase 2 proteins, which increase following exposure to hypoxia, were dose-dependently down-regulated by melatonin treatment. Melatonin also blocked the hypoxic responses that reduced pro-apoptotic proteins and increased anti-apoptotic proteins including Bcl-2 and Bcl-xL. Furthermore, melatonin treatment reduced TRAIL resistance by regulating the mitochondrial transmembrane potential and Bax translocation. Our results first demonstrated that melatonin treatment induces apoptosis in TRAIL-resistant hypoxic tumor cells by diminishing the anti-apoptotic signals mediated by hypoxia and also suggest that melatonin could be a tumor therapeutic tool by combining with other apoptotic ligands including TRAIL, particularly in solid tumor cells exposed to hypoxia.

  6. Hypoxic Tumor Can be More Responsive to Fractionated Irradiation Combined with SR 4233 (Tirapazamine)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Il Han [Seoul National University College of Medicine, Seoul (Korea, Republic of); Brown, J. Martin [Stanford Univ., Stanford (United States)

    1994-02-15

    Hypothesis that hypoxic tumors should be more responsive to the addition of preferential hypoxic cell cytotoxin SR 4233 (tirapazamine) to fractionated irradiation was tested in the mouse SCCVII carcinoma and RIF-1 sarcoma, Model of hypoxic tumor was established using the tumor bed effect; tumors growing in the preirradiated tissue (preirradiated tumors) were more hypoxic than tumors growing in the unirradiated tissue (unirradiated tumors). When the tumors reached a mean volume of 100 mm{sup 3}, both unirradiated and preirradiated tumors were treated with a fractionated course of 6 x 2 Gy in 3 days or 8 x2.5 Gy in 4 days with SR 4233 (0.08m mol/kg/injection) given 30 minutes before each irradiation or without SR 4233. Compared to the unirradiated tumors, hypoxic preirradiated tumors were approximately 5 times more resistant to fractionated irradiation alone but were approximately 5 times more responsive to SR 4233. Addition of SR 4233 potentiated the effect of fractionated irradiation in both unirradiated and preirradiated tumors. Potentiation in the preirradiated tumors was morequal to or greater than that in the unirradiated tumors and seemed to be higher for more fractionated treatment. We confirm the hypothesis in a transplantable mouse tumor. Present results suggest that radioresistance of some hypoxic tumors can be overcome with hypoxic cytotoxin.

  7. Carbohydrate Supplementation Influences Serum Cytokines after Exercise under Hypoxic Conditions

    Directory of Open Access Journals (Sweden)

    Aline Venticinque Caris

    2016-11-01

    Full Text Available Introduction: Exercise performed at the hypoxia equivalent of an altitude of 4200 m is associated with elevated inflammatory mediators and changes in the Th1/Th2 response. By contrast, supplementation with carbohydrates has an anti-inflammatory effect when exercise is performed under normoxic conditions. The objective of this study was to evaluate the effect of carbohydrate supplementation on cytokines and cellular damage markers after exercise under hypoxic conditions at a simulated altitude of 4200 m. Methods: Seven adult male volunteers who exercised for 60 min at an intensity of 50% VO2Peak were randomly evaluated under three distinct conditions; normoxia, hypoxia and hypoxia + carbohydrate supplementation. Blood samples were collected at rest, at the end of exercise and after 60 min of recovery. To evaluate hypoxia + carbohydrate supplementation, volunteers received a solution of 6% carbohydrate (maltodextrin or a placebo (strawberry-flavored Crystal Light®; Kraft Foods, Northfield, IL, USA every 20 min during exercise and recovery. Statistical analyses comprised analysis of variance, with a one-way ANOVA followed by the Tukey post hoc test with a significance level of p < 0.05. Results: Under normoxic and hypoxic conditions, there was a significant increase in the concentration of IL-6 after exercise and after recovery compared to at rest (p < 0.05, while in the hypoxia + carbohydrate group, there was a significant increase in the concentration of IL-6 and TNF-α after exercise compared to at rest (p < 0.05. Furthermore, under this condition, TNF-α, IL-2 and the balance of IL-2/IL-4 were increased after recovery compared to at rest (p < 0.05. Conclusion: We conclude that carbohydrate supplementation modified the IL-6 and TNF-α serum concentrations and shifted the IL-2/IL-4 balance towards Th1 in response without glycemic, glutaminemia and cell damage effects.

  8. Karyopherin alpha2: a control step of glucose-sensitive gene expression in hepatic cells.

    Science.gov (United States)

    Guillemain, Ghislaine; Muñoz-Alonso, Maria J; Cassany, Aurélia; Loizeau, Martine; Faussat, Anne-Marie; Burnol, Anne-Françoise; Leturque, Armelle

    2002-05-15

    Glucose is required for an efficient expression of the glucose transporter GLUT2 and other genes. We have shown previously that the intracytoplasmic loop of GLUT2 can divert a signal, resulting in the stimulation of glucose-sensitive gene transcription. In the present study, by interaction with the GLUT2 loop, we have cloned the rat karyopherin alpha2, a receptor involved in nuclear import. The specificity of the binding was restricted to GLUT2, and not GLUT1 or GLUT4, and to karyopherin alpha2, not alpha1. When rendered irreversible by a cross-linking agent, this transitory interaction was detected in vivo in hepatocytes. A role for karyopherin alpha2 in the transcription of two glucose-sensitive genes was investigated by transfection of native and inactive green fluorescent protein-karyopherin alpha2 in GLUT2-expressing hepatoma cells. The amount of inactive karyopherin alpha2 receptor reduced, in a dose-dependent manner, the GLUT2 and liver pyruvate kinase mRNA levels by competition with endogenous active receptor. In contrast, the overexpression of karyopherin alpha2 did not significantly stimulate GLUT2 and liver pyruvate kinase mRNA accumulation in green fluorescent protein-sorted cells. The present study suggests that, in concert with glucose metabolism, karyopherin alpha2 transmits a signal to the nucleus to regulate glucose-sensitive gene expression. The transitory tethering of karyopherin alpha2 to GLUT2 at the plasma membrane might indicate that the receptor can load the cargo to be imported locally.

  9. Interval hypoxic training in complex treatment of fractures of trochanteric area of the femur

    Directory of Open Access Journals (Sweden)

    Василь Михайлович Шимон

    2015-05-01

    Full Text Available The method of interval hypoxic training (IHT is used to increase physical endurance of athletes and for treatment of certain systemic diseases, due to the ability of IHT affect metabolism, homeostasis and the immune system. The aims of the article are improving the results of treatment and rehabilitation of patients with fractures of the trochanteric area of the femur by the method of interval hypoxic training and study its influence on bone metabolism.Materials and methods. 17 patients who were hospitalized in the clinic of general surgery UzhNU with fractures of the trochanteric area of the femur are examined in the period from 2012 to 2015.The first group consisted of 6 patients who from day-patient treatment is conducted IHT by gas mixture of 12 % oxygen. The second group consisted of 4 patients with thyrotoxicosis who are also receiving IHT by gas mixture of 12% oxygen.The control group consisted of 7 patients with fractures of the trochanteric area of the femur who refused from IHT.Results and its discussion. The best physical activity is observed in the first group. Starting physical activity is the lowest in the second group, but its development is faster. Slowly increase the duration of physical activity compared with the first two groups is observed in the control group.In the control study after 1 month it is noted that calcium level increased in all three groups. Increase in the second group is biggest. The level of phosphorus decreased in the first and the control group and increased in the second group.The levels of osteocalcin and alkaline phosphatase increased. Rates were higher and increase was substantial in the first two groups in comparison with the control group.Conclusions.• Intensive growth of length of one-time physical activity most notably in patients with thyrotoxicosis is observed in patients who are receiving IHT.• Improvement of the activity of bone metabolism is observed in patients after IHT

  10. Expression of bone morphogenetic protein 7 in the cerebral cortex of rats after ischemic-hypoxic injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Some researches demonstrate that exogenous bone morphogenetic protein 7 (BMP-7) can protect ischemic cerebral nerve tissue and promote recovery of motor energy function; however, there is lack of direct evidences of endogenous BMP-7 effect.OBJECTIVE: To observe the expression of endogenous BMP-7 in nerve tissue with ischemic-hypoxic injury and investigate the possible effects on damaged nerve tissue.DESIGN: Observational contrast animal study.SETTING: Department of Anatomy and Histoembryology, Peking University Health Science Center.MATERIALS: The experiment was carried out in the Nerve Researching Laboratory of Anatomy Department, Peking University Health Science Center from October 2006 to March 2007. A total of 25 adult male SD rats weighing 250 - 300 g and several newborn SD rats were selected from Experimental Animal Center, Peking University Health Science Center. Rabbit-anti-BMP-7 polyclonal antibody was provided by Wuhan Boster Company.METHODS: ① Adult rats were randomly divided into ischemia group (n =10), sham operation group (n =10) and normal group (n =5). Right external-internal carotid artery occlusion was used to infarct middle cerebral artery of adult rats in the ischemia group so as to copy focal cerebral infarction models. Line cork was inserted in crotch of internal and external carotid artery of adult rats in the sham operation group, while adult rats in the normal group were not given any treatments. ② Cerebral cortex of newborn rats was separated to obtain cell suspension. Cells which were cultured for 10 days were divided into control group and hypoxia/reoxygenation group. And then, cells in the hypoxia/reoxygenation group were cultured in hypoxic incubator for 4 hours and given reoxygenation for 24 hours.MAIN OUTCOME MEASURES: Immunohistochemical method was used to measure expression of BMP-7 in cerebral cortex at 24 hours after ischemia/reperfusion culture and in primary hypoxic culture.RESULTS: ① At 24 hours after

  11. Hypoxic preconditioning differentially affects GABAergic and glutamatergic neuronal cells in the injured cerebellum of the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Sergio G Benitez

    Full Text Available In this study we examined cerebellar alterations in a neonatal rat model of hypoxic-ischemic brain injury with or without hypoxic preconditioning (Pc. Between postnatal days 7 and 15, the cerebellum is still undergoing intense cellular proliferation, differentiation and migration, dendritogenesis and synaptogenesis. The expression of glutamate decarboxylase 1 (GAD67 and the differentiation factor NeuroD1 were examined as markers of Purkinje and granule cells, respectively. We applied quantitative immunohistochemistry to sagittal cerebellar slices, and Western blot analysis of whole cerebella obtained from control (C rats and rats submitted to Pc, hypoxia-ischemia (L and a combination of both treatments (PcL. We found that either hypoxia-ischemia or Pc perturbed the granule cells in the posterior lobes, affecting their migration and final placement in the internal granular layer. These effects were partially attenuated when the Pc was delivered prior to the hypoxia-ischemia. Interestingly, whole nuclear NeuroD1 levels in Pc animals were comparable to those in the C rats. However, a subset of Purkinje cells that were severely affected by the hypoxic-ischemic insult--showing signs of neuronal distress at the levels of the nucleus, cytoplasm and dendritic arborization--were not protected by Pc. A monoclonal antibody specific for GAD67 revealed a three-band pattern in cytoplasmic extracts from whole P15 cerebella. A ∼110 kDa band, interpreted as a potential homodimer of a truncated form of GAD67, was reduced in Pc and L groups while its levels were close to the control animals in PcL rats. Additionally we demonstrated differential glial responses depending on the treatment, including astrogliosis in hypoxiated cerebella and a selective effect of hypoxia-ischemia on the vimentin-immunolabeled intermediate filaments of the Bergmann glia. Thus, while both glutamatergic and GABAergic cerebellar neurons are compromised by the hypoxic-ischemic insult

  12. Increasing LIGO sensitivity by feedforward subtraction of auxiliary length control noise

    Science.gov (United States)

    Meadors, Grant; Kawabe, Keita; Riles, Keith

    2013-04-01

    LIGO, the Laser Interferometer Gravitational-wave Observatory [Hanford, Washington and Livingston, Louisiana] measures the differential length of 4-km Michelson arms with Fabry-Perot cavities. Length changes could indicate strain caused by astrophysical sources of gravitational waves. Fundamentally limited by seismic noise, thermal suspension noise, and laser shot noise in different frequency bands, a LIGO interferometer's sensitivity can also be degraded by additional relative motion of the inner arm cavity mirrors due to imperfectly-servoed Michelson motion. In this project we seek to subtract the effects of this residual motion by feedforward correction of the gravitational-wave data channel. We divide data from LIGO's sixth science run into 1024-second time windows and numerically fit a filter representing the frequency-domain transfer function from Michelson servo noise to gravitational wave channel for each window. Finally, the Michelson servo channel is processed through the filter and is subtracted from the gravitational-wave signal channel. The algorithm used in this procedure will be described with a preliminary assessment of the achievable sensitivity improvement.

  13. Proximity-based access control for context-sensitive information provision in SOA-based systems

    Science.gov (United States)

    Rajappan, Gowri; Wang, Xiaofei; Grant, Robert; Paulini, Matthew

    2014-06-01

    Service Oriented Architecture (SOA) has enabled open-architecture integration of applications within an enterprise. For net-centric Command and Control (C2), this elucidates information sharing between applications and users, a critical requirement for mission success. The Information Technology (IT) access control schemes, which arbitrate who gets access to what information, do not yet have the contextual knowledge to dynamically allow this information sharing to happen dynamically. The access control might prevent legitimate users from accessing information relevant to the current mission context, since this context may be very different from the context for which the access privileges were configured. We evaluate a pair of data relevance measures - proximity and risk - and use these as the basis of dynamic access control. Proximity is a measure of the strength of connection between the user and the resource. However, proximity is not sufficient, since some data might have a negative impact, if leaked, which far outweighs importance to the subject's mission. For this, we use a risk measure to quantify the downside of data compromise. Given these contextual measures of proximity and risk, we investigate extending Attribute-Based Access Control (ABAC), which is used by the Department of Defense, and Role-Based Access Control (RBAC), which is widely used in the civilian market, so that these standards-based access control models are given contextual knowledge to enable dynamic information sharing. Furthermore, we consider the use of such a contextual access control scheme in a SOA-based environment, in particular for net-centric C2.

  14. Decursin reduce radio-resistance of hypoxic regions under the proton beam therapy by induced HIF-1α degradation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Hwan; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    Protons induce cancer-cell apoptosis in vitro and block blood vessel formation in vivo through the generation of reactive oxygen species (ROS). The fact that proton severely inhibits blood vessel development in zebrafish embryos suggests a higher sensitivity of vascular endothelial cells to proton beam. Decursin, a coumarin compound, was originally isolated from Angelica gigas Nakai (Dang Gui). A. gigas root has been traditionally used in Korean folk medicine for the treatment of anemia and other common diseases. In previous reports, decursin was reported to exhibit anti-tumor activity against various cancer cells and to inhibit the activities of the androgen and androgen-receptor (AR) signaling pathway in prostate cancer, induction of cell cycle arrest and apoptosis in various cancer cells, such as prostate, breast, bladder, and colon cancer cells. Decursin also inhibits VEGF-induced angiogenesis through the suppression of the VEGFR-2-signaling pathway. However, the mechanism of decursin mediates change of HIF-1α activities is not clear. In this research, we identified regulations of the HIF-1α and the anti-angiogenesis effects of decursin in proton-beam-irradiated human lung cancer, prostate cancer and Hepatic cancer cells. We investigated the underlying mechanisms of positive effects of protonbeam-induced anti-angiogenesis. Our data indicate that the groups co-treated with decursin and a proton-beam had significant reduced HIF-1α activity compared with the groups treated with only a proton beam under the hypoxic condition caused by DFX(desferrioxamine). Decursin was found to induced HIF-1α degradation. Therefore, we suggest that decursin may be a potential candidate for use as a sensitizer for proton-beaminduced cell apoptosis. Here we have shown that decursin successfully reduced HIF-1α stability under hypoxic condition by induced desferrioxamine. We showed novel candidates for anti-angiogenic compound, decursin, leading to complete inhibition of radio

  15. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  16. Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

    Science.gov (United States)

    Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

    2014-08-01

    Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage.

  17. Hypoxic Exercise Training Promotes apelin/APJ Expression in Skeletal Muscles of High Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Ji, Weixiu; Gong, Lijing; Wang, Jianxiong; He, Hui; Zhang, Ying

    2017-01-01

    Apelin, an endogenous ligand of the G-protein-coupled receptor APJ, is a novel myokine and may play a key role in regulating energy metabolism. The purpose of the present study was to investigate the effects of hypoxic exposure, exercise, and hypoxic exercise training on the expression of apelin and APJ in skeletal muscle of obese mice. Sixty two-months old C57BL/6J mice were randomly divided into two groups: Ten in normal diet group (N) and 50 in the high fat diet (HFD) groups. After two months of feeding, the HFD mice, whose body weight was 20% higher than the average weight of the N group, were selected as obese mice and further allocated into four groups: Control (C), Exercise (E), Hypoxia (H), and Exercise plus Hypoxia (E+H), at 8-9 mice/group. Besides body weight, measured variables in skeletal muscle were protein/mRNA levels of apelin/APJ, AMPKα-Thr172 phosphorylation, hypoxia inducible factor-1α (HIF-1α), mRNA levels of peroxisome proliferator-activated receptor α (PPARα), estrogen-related receptor (ERRα), and nuclear respiratory factor 1 (NRF1). Obese mice had significantly lower mRNA and protein expressions of apelin/ APJ in skeletal muscles than the normal body weight mice. After four weeks of interventions, hypoxic exercise training decreased body weight and increased mRNA and protein expressions of apelin and APJ, mRNA expression of ERRα, and protein expression of HIF-1α. These results indicate that changes of body weight may be associated with the levels of apelin/APJ expressions in skeletal muscle. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Delay-Sensitive Distributed Power and Transmission Threshold Control for S-ALOHA Network with Finite State Markov Fading Channels

    CERN Document Server

    Huang, Huang

    2009-01-01

    In this paper, we consider the delay-sensitive power and transmission threshold control design in S-ALOHA network with FSMC fading channels. The random access system consists of an access point with K competing users, each has access to the local channel state information (CSI) and queue state information (QSI) as well as the common feedback (ACK/NAK/Collision) from the access point. We seek to derive the delay-optimal control policy (composed of threshold and power control). The optimization problem belongs to the memoryless policy K-agent infinite horizon decentralized Markov decision process (DEC-MDP), and finding the optimal policy is shown to be computationally intractable. To obtain a feasible and low complexity solution, we recast the optimization problem into two subproblems, namely the power control and the threshold control problem. For a given threshold control policy, the power control problem is decomposed into a reduced state MDP for single user so that the overall complexity is O(NJ), where N a...

  19. Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Toru; Shibamoto, Yuta; Sasai, Keisuke; Oya, Natsuo; Murata, Rumi; Takagi, Takehisa; Hiraoka, Masahiro [Kyoto Univ. (Japan). Chest Disease Research Inst.; Abe, Mitsuyuki

    1996-01-01

    Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of promising hypoxic cytotoxin, tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide), were examined in comparison with those of KU-2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo-in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT-6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single-dose irradiation (18 Gy), both tirapazamine and KU-2285 showed significant enhancement of cell killing in a dose-dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU-2285 was more effective for EMT-6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU-2285 at 100-200 mg/kg in both SCCVII and EMT-6/KU tumors. We concluded that the effectiveness of KU-2285 and tirapazamine was correlated with the nature of tumor hypoxia with single-dose irradiation, whereas tirapazamine appeared more potent than KU-2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy. (author).

  20. Control of the sensitivity of CRLH interdigital microstrip balanced structures using a co-design genetic algorithm approach

    Science.gov (United States)

    Siragusa, R.; Perret, E.; Nguyen, H. V.; Lemaître-Auger, P.; Tedjini, S.; Caloz, C.

    2011-06-01

    A fully automated tool for designing CRLH interdigital microstrip structures using a co-design synthesis computational approach is proposed and demonstrated experimentally. This approach uses an electromagnetic simulator in conjunction with a genetic algorithm to synthesize and optimize a balanced CRLH interdigital microstrip transmission line. The high sensitivity of a long balanced transmission line to fabrication tolerances is controlled by the use of a high precision 3D simulator. The 2.5D simulator used was found insufficient for a large number of unit cells. A 13 UC CRLH transmission line is designed with the proposed approach. The response sensitivity of the balanced transmission lines to the over/under-etching factor is highlighted by comparing the measurements of four lines with different factors. The effect of over/under-etching is significant for values larger than 10 μm.

  1. Computation of eigenvalue sensitivity to base flow modifications in a discrete framework: Application to open-loop control

    CERN Document Server

    Mettot, Clément; Sipp, Denis

    2014-01-01

    A fully discrete formalism is introduced to perform stability analysis of a turbulent compressible flow whom dynamics is modeled with the Reynolds-Averaged Navier-Stokes (RANS) equations. The discrete equations are linearized using finite differences and the Jacobian is computed using repeated evaluation of the residuals. Stability of the flow is assessed solving an eigenvalue problem. The sensitivity gradients which indicate regions of the flow where a passive control device could stabilize the unstable eigenvalues are defined within this fully discrete framework. Second order finite differences are applied to the discrete residual to compute the gradients. In particular, the sensitivity gradients are shown to be linked to the Hessian of the RANS equations. The introduced formalism and linearization method are generic: the code used to evaluate the residual of the RANS equations can be used in a black box manner, and the complex linearization of the Hessian is avoided. The method is tested on a two dimension...

  2. Mobile technology habits: patterns of association among device usage, intertemporal preference, impulse control, and reward sensitivity.

    Science.gov (United States)

    Wilmer, Henry H; Chein, Jason M

    2016-10-01

    Mobile electronic devices are playing an increasingly pervasive role in our daily activities. Yet, there has been very little empirical research investigating how mobile technology habits might relate to individual differences in cognition and affect. The research presented in this paper provides evidence that heavier investment in mobile devices is correlated with a relatively weaker tendency to delay gratification (as measured by a delay discounting task) and a greater inclination toward impulsive behavior (i.e., weaker impulse control, assessed behaviorally and through self-report) but is not related to individual differences in sensitivity to reward. Analyses further demonstrated that individual variation in impulse control mediates the relationship between mobile technology usage and delay of gratification. Although based on correlational results, these findings lend some backing to concerns that increased use of portable electronic devices could have negative impacts on impulse control and the ability to appropriately valuate delayed rewards.

  3. A novel frequency control scheme for comb-referenced sensitive difference-frequency-generation spectroscopy.

    Science.gov (United States)

    Iwakuni, Kana; Okubo, Sho; Sasada, Hiroyuki

    2013-06-17

    We present a novel scheme of frequency scan and wavelength modulation of a difference-frequency-generation source for comb-referenced sensitive spectroscopy. While the pump and signal frequencies are phase-locked to an optical frequency comb (OFC), the offset frequency between the signal wave and the nearest comb tooth is modulated to apply a wavelength-modulation technique, and the idler wave frequency is repeatedly swept for signal accumulation by changing the repetition frequency of the OFC. The spectrometer is applied to absolute frequency measurement of weak hyperfine-resolved rovibration transitions of the ν(1) band of CH(3)I, and the uncertainty in frequency determination is reduced by one order of magnitude in compared with that of the previous work published in Optics Express 20, 9178-9186 (2012).

  4. Conduction band energy level control of titanium dioxide: toward an efficient visible-light-sensitive photocatalyst.

    Science.gov (United States)

    Yu, Huogen; Irie, Hiroshi; Hashimoto, Kazuhito

    2010-05-26

    Through the use of a strategy that involves narrowing the TiO(2) band gap by shifting its conduction band positively and utilizing the catalytic activity of photoproduced Cu(I) for oxygen reduction, a novel visible-light-sensitive TiO(2) photocatalyst, Cu(II)-grafted Ti(1-3x)W(x)Ga(2x)O(2), was designed and synthesized. The Cu(II)/Ti(1-3x)W(x)Ga(2x)O(2) photocatalyst produced high activity under visible-light irradiation. In fact, it decomposed 2-propanol to CO(2) via acetone under visible light (>400 nm) with a high quantum efficiency of 13%. The turnover number for this reaction exceeded 22, indicating that it functioned catalytically.

  5. Strategizing the clone wars: pharmacological control of cellular sensitivity to radiation.

    Science.gov (United States)

    Kimple, Randall J

    2010-12-01

    The combined administration of ionizing radiation and systemic chemotherapy is an accepted standard of care for numerous cancers. Improved efficacy through the combination of therapies reflects several interrelated processes, including DNA damage, inhibition of DNA synthesis, alteration of cell cycle distribution, and impaired DNA repair. Insights into cellular responses to radiation have led to the use of drugs that target specific intracellular signaling pathways to sensitize cells to radiation. Combinations of chemotherapy and radiation continue to be optimized, based on preclinical and early-phase clinical data that indicate the ideal sequencing of therapies, the best combinations of agents (including radiosensitizers), and the most reliable biological markers for predicting patient responsiveness. This review summarizes our current understanding of radiosensitization as it relates to preclinical drug development and discusses the potential benefits of judiciously incorporating both traditional and targeted chemotherapy into radiation regimens.

  6. 肿瘤坏死因子α、超敏C反应蛋白在新生儿缺氧缺血性脑病中的变化及临床意义%Changes and clinical significance of tumor necrosis factor-αand high-sensitivity C-reactive protein in neonates with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    尚云; 石计朋; 杨卫红; 马慧敏; 郭喜霞; 唐成和

    2016-01-01

    Objective To investigate the potential roles of tumor necrosis factorα(TNF-α)and highsensitivity Creactive protein (HsCRP)in the progression and prognosis of neonatal hypoxicischemic encephalopathy(HIE).Methods This study was a clinical ex-perimental study.Totally 74 cases of neonates with HIE diagnosed in the First Affiliated Hospital of Xinxiang Medical University From February 2011 to February 2013 were enrolled as observation group (mild 31 cases,moderate 26 cases,severe 17 cases;32 cases with good prognosis,42 poor prognosis),and another 74 cases of normal healthy neonates were selected as control group.The levels of TNF-αand HsCRP in all samples were measured 48 hours after being born by enzymelinked immunosorbent assay (ELISA)and radio immu-noassay (RIA)method.Results The data revealed significant upregulation of the serum levels of TNF-αand HsCRP in patients with HIE.The increase in the levels of these inflammatory mediators correlated with the severity of the disease and also had a positive corre-lation with the prognosis of the disease.Serum levels of TNF-αand HsCRP in HIE group were significantly higher than those in normal control group.TNF-αlevels were 17.20 ±1.26 vs 97.00 ±5.97 ng·L -1 (P <0.05);HsCRP levels were 0.51 ±0.18 vs 11.93 ± 1.91 mg·L -1 (P <0.05).Serum levels of TNF-αand HsCRP in the moderate and severe patient groups were significantly higher compared with those in the mild group(P <0.05).Furthermore,there was a significant upregulation of the cytokines in the severe group compared with those in the moderate group(P <0.05).The differences among 3 groups were also significant ,and they were the highest with severe HIE,TNF-αlevels(mild group 31.37 ±3.28 vs moderate group 52.59 ±5.19 vs severe group 102.65 ±7.81 ng·L -1 ,P<0.05);HsCRP levels(mild group 4.63 ±0.69 vs moderate group 7.56 ±1.19 vs severe group 12.92 ±3.25 mg·L -1 ,P <0.05).Comparison of the serum levels of TNF-αand HsCRP in patients with different

  7. Angiotensin II (de)sensitization: Fluid intake studies with implications for cardiovascular control.

    Science.gov (United States)

    Daniels, Derek

    2016-08-01

    Cardiovascular disease is the leading cause of death worldwide and hypertension is the most common risk factor for death. Although many anti-hypertensive pharmacotherapies are approved for use in the United States, rates of hypertension have increased over the past decade. This review article summarizes a presentation given at the 2015 meeting of the Society for the Study of Ingestive Behavior. The presentation described work performed in our laboratory that uses angiotensin II-induced drinking as a model system to study behavioral and cardiovascular effects of the renin-angiotensin system, a key component of blood pressure regulation, and a common target of anti-hypertensives. Angiotensin II (AngII) is a potent dipsogen, but the drinking response shows a rapid desensitization after repeated injections of AngII. This desensitization appears to be dependent upon the timing of the injections, requires activation of the AngII type 1 (AT1) receptor, requires activation of mitogen-activated protein (MAP) kinase family members, and involves the anteroventral third ventricle (AV3V) region as a critical site of action. Moreover, the response does not appear to be the result of a more general suppression of behavior, a sensitized pressor response to AngII, or an aversive state generated by the treatment. More recent studies suggest that the treatment regimen used to produce desensitization in our laboratory also prevents the sensitization that occurs after daily bolus injections of AngII. Our hope is that these findings can be used to support future basic research on the topic that could lead to new developments in treatments for hypertension.

  8. An Isolation Method for Assessment of Brain Mitochondria Function in Neonatal Mice with Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Caspersen, Casper S.; Sosunov, Alexander; Utkina-Sosunova, Irina; Ratner, Veniamin I.; Starkov, Anatoly A.; Ten, Vadim S.

    2010-01-01

    This work was undertaken to develop a method for the isolation of mitochondria from a single cerebral hemisphere in neonatal mice. Mitochondria from the normal mouse brain hemisphere isolated by the proposed method exhibited a good respiratory control ratio of 6.39 ± 0.53 during glutamate-malate-induced phosphorylating respiration. Electron microscopy showed intact mitochondria. The applicability of this method was tested on mitochondria isolated from naïve mice and their littermates subjected to hypoxic-ischemic insult. Hypoxic-ischemic insult prior to reperfusion resulted in a significant (p < 0.01) inhibition of phosphorylating respiration compared to naïve littermates. This was associated with a profound depletion of the ATP content in the ischemic hemisphere. The expression for Mn superoxide dismutase and cytochrome C (markers for the integrity of the mitochondrial matrix and outer membrane) was determined by Western blot to control for mitochondrial integrity and quantity in the compared samples. Thus, we have developed a method for the isolation of the cerebral mitochondria from a single hemisphere adapted to neonatal mice. This method may serve as a valuable tool to study mitochondrial function in a mouse model of immature brain injury. In addition, the suggested method enables us to examine the mitochondrial functional phenotype in immature mice with a targeted genetic alteration. PMID:18349523

  9. Wide Area Prosumption Control and Sensitivities of Aperiodic Small Signal Stability Indicators

    DEFF Research Database (Denmark)

    Wittrock, Martin Lindholm; Jóhannsson, Hjörtur; Nielsen, Arne Hejde

    2014-01-01

    and patterns, stability indicators for aperiodic small signal angular stability (ASSA) are examined, while the concept of prosumption is described. The methodology presented is shown to be able to assess the margin to instability and to predict how this margin can be affected if a load is changed in the grid......This paper introduces the concept of prosumption control where intelligent loads and distributed generation are aggregated and controlled to improve power system security. It is expected that intelligent load and generation units can respond to control / market signals and thus present...... an opportunity of available resources for changing the operating point (OP) of a system to one that is more secure. A prosumption pattern is then a signal to prosumers to shift their demand in time. This makes it possible to temporarily change the distribution of the power demand. A prosumption pattern...

  10. Queue-Aware Distributive Resource Control for Delay-Sensitive Two-Hop MIMO Cooperative Systems

    CERN Document Server

    Wang, Rui; Cui, Ying

    2010-01-01

    In this paper, we consider a queue-aware distributive resource control algorithm for two-hop MIMO cooperative systems. We shall illustrate that relay buffering is an effective way to reduce the intrinsic half-duplex penalty in cooperative systems. The complex interactions of the queues at the source node and the relays are modeled as an average-cost infinite horizon Markov Decision Process (MDP). The traditional approach solving this MDP problem involves centralized control with huge complexity. To obtain a distributive and low complexity solution, we introduce a linear structure which approximates the value function of the associated Bellman equation by the sum of per-node value functions. We derive a distributive two-stage two-winner auction-based control policy which is a function of the local CSI and local QSI only. Furthermore, to estimate the best fit approximation parameter, we propose a distributive online stochastic learning algorithm using stochastic approximation theory. Finally, we establish techn...

  11. Kalkitoxin Inhibits Angiogenesis, Disrupts Cellular Hypoxic Signaling, and Blocks Mitochondrial Electron Transport in Tumor Cells

    Directory of Open Access Journals (Sweden)

    J. Brian Morgan

    2015-03-01

    Full Text Available The biologically active lipopeptide kalkitoxin was previously isolated from the marine cyanobacterium Moorea producens (Lyngbya majuscula. Kalkitoxin exhibited N-methyl-d-aspartate (NMDA-mediated neurotoxicity and acted as an inhibitory ligand for voltage-sensitive sodium channels in cultured rat cerebellar granule neurons. Subsequent studies revealed that kalkitoxin generated a delayed form of colon tumor cell cytotoxicity in 7-day clonogenic cell survival assays. Cell line- and exposure time-dependent cytostatic/cytotoxic effects were previously observed with mitochondria-targeted inhibitors of hypoxia-inducible factor-1 (HIF-1. The transcription factor HIF-1 functions as a key regulator of oxygen homeostasis. Therefore, we investigated the ability of kalkitoxin to inhibit hypoxic signaling in human tumor cell lines. Kalkitoxin potently and selectively inhibited hypoxia-induced activation of HIF-1 in T47D breast tumor cells (IC50 5.6 nM. Mechanistic studies revealed that kalkitoxin inhibits HIF-1 activation by suppressing mitochondrial oxygen consumption at electron transport chain (ETC complex I (NADH-ubiquinone oxidoreductase. Further studies indicate that kalkitoxin targets tumor angiogenesis by blocking the induction of angiogenic factors (i.e., VEGF in tumor cells.

  12. Using Simulation Module, PCLAB, for Steady State Disturbance Sensitivity Analysis in Process Control

    Science.gov (United States)

    Ali, Emad; Idriss, Arimiyawo

    2009-01-01

    Recently, chemical engineering education moves towards utilizing simulation soft wares to enhance the learning process especially in the field of process control. These training simulators provide interactive learning through visualization and practicing which will bridge the gap between the theoretical abstraction of textbooks and the…

  13. Using Simulation Module, PCLAB, for Steady State Disturbance Sensitivity Analysis in Process Control

    Science.gov (United States)

    Ali, Emad; Idriss, Arimiyawo

    2009-01-01

    Recently, chemical engineering education moves towards utilizing simulation soft wares to enhance the learning process especially in the field of process control. These training simulators provide interactive learning through visualization and practicing which will bridge the gap between the theoretical abstraction of textbooks and the…

  14. Value sensitive design of automated workload distribution support for traffic control teams

    NARCIS (Netherlands)

    Harbers, M.; Neerincx, M.A.

    2014-01-01

    This paper studies the effects of automated support for workload distribution in traffic control teams on human values such as security, autonomy and privacy. The paper describes a workshop in which the support system's stakeholders, their values, and the effects of the support system on these value

  15. Increasing the sensitivity of controlled-source electromagnetics with synthetic aperture

    NARCIS (Netherlands)

    Fan, Y.; Snieder, R.; Slob, E.C.; Hunziker, J.W.; Singer, J.; Sheiman, J.; Rosenquist, M.

    2012-01-01

    Controlled-source electromagnetics (CSEM) has been used as a derisking tool in the hydrocarbon exploration industry. We apply the concept of synthetic aperture to the lowfrequency electromagnetic field in CSEM. Synthetic aperture sources have been used in radar imaging for many years. Using the synt

  16. pH-controllable synthesis of unique nanostructured tungsten oxide aerogel and its sensitive glucose biosensor.

    Science.gov (United States)

    Sun, Qiang-Qiang; Xu, Maowen; Bao, Shu-Juan; Li, Chang Ming

    2015-03-20

    This work presents a controllable synthesis of nanowire-networked tungsten oxide aerogels, which was performed by varying the pH in a polyethyleneimine (PEI)-assisted hydrothermal process. An enzyme-tungsten oxide aerogel co-modified electrode shows high activity and selectivity toward glucose oxidation, thus holding great promise for applications in bioelectronics.

  17. Impact of cable bacteria on sedimentary iron and manganese dynamics in a seasonally-hypoxic marine basin

    Science.gov (United States)

    Sulu-Gambari, Fatimah; Seitaj, Dorina; Behrends, Thilo; Banerjee, Dipanjan; Meysman, Filip J. R.; Slomp, Caroline P.

    2016-11-01

    results confirm that cable bacteria act as a key control on the coupled cycling of Fe and Mn in surface sediments of seasonally hypoxic basins.

  18. Spatiotemporal Characteristics of Freezing of Gait in Patients After Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Yoon, Seo Yeon; Lee, Sang Chul; Kim, Yong Wook

    2016-01-01

    Abstract The objective of this study was to investigate spatiotemporal characteristics with gait variability in patients with freezing of gait (FOG) after hypoxic-ischemic brain injury (HIBI). Eleven patients showing FOG after HIBI and 15 normal controls were consecutively enrolled. We performed gait analysis using a computerized gait system (VICON MX-T10 Motion Analysis System) and compared spatiotemporal characteristics and gait variability in both groups. Additionally, we performed correlation analysis to identify the gait parameters associated with severity of freezing, which we measured based on unified Parkinson disease Rating Scale subscore. Spatiotemporal characteristic of FOG patients showed increased stance time and double support phase and decreased swing time, single support phase, stride length, step length, and gait velocity compared with normal controls (P step length asymmetry were significantly increased in HIBI patients with FOG (P step length, and gait velocity variability in HIBI patients with FOG compared with normal controls (P step length, and single support phase to be spatiotemporal parameters related to FOG severity (P < 0.05). Our findings suggest that bilateral gait coordination deterioration plays a considerable role for pathophysiology of FOG in HIBI patients. Additional studies with a larger number of subjects are needed to further investigate the neural mechanism of FOG after HIBI. PMID:27175696

  19. Controlling Explosive Sensitivity of Energy-Related Materials by Means of Production and Processing in Electromagnetic Fields

    Science.gov (United States)

    Rodzevich, A. P.; Gazenaur, E. G.; Kuzmina, L. V.; Krasheninin, V. I.; Sokolov, P. N.

    2016-08-01

    The present work is one of the world first attempts to develop effective methods for controlling explosive sensitivity of energy-related materials with the help of weak electric (up to 1 mV/cm) and magnetic (0.001 T) fields. The resulting experimental data can be used for purposeful alternation of explosive materials reactivity, which is of great practical importance. The proposed technology of producing and processing materials in a weak electric field allows forecasting long-term stability of these materials under various energy impacts.

  20. A Qualitative Study of Physician Perspectives on Prognostication in Neonatal Hypoxic Ischemic Encephalopathy.

    Science.gov (United States)

    Rasmussen, Lisa Anne; Bell, Emily; Racine, Eric

    2016-10-01

    Hypoxic ischemic encephalopathy is the most frequent cause of neonatal encephalopathy and yields a great degree of morbidity and mortality. From an ethical and clinical standpoint, neurological prognosis is fundamental in the care of neonates with hypoxic ischemic encephalopathy. This qualitative study explores physician perspectives about neurological prognosis in neonatal hypoxic ischemic encephalopathy. This study aimed, through semistructured interviews with neonatologists and pediatric neurologists, to understand the practice of prognostication. Qualitative thematic content analysis was used for data analysis. The authors report 2 main findings: (1) neurological prognosis remains fundamental to quality-of-life predictions and considerations of best interest, and (2) magnetic resonance imaging is presented to parents with a greater degree of certainty than actually exists. Further research is needed to explore both the parental perspective and, prospectively, the impact of different clinical approaches and styles to prognostication for neonatal hypoxic ischemic encephalopathy.

  1. Hypoxic training for swimmer's combined team preparation of the law university

    Directory of Open Access Journals (Sweden)

    Balamutova N.M.

    2012-03-01

    Full Text Available The matters of the hypoxic training for highly qualified swimmers as extra means of improving level for sports achievements were considered. A method of artificial hypoxic training that increase indexes of cardiorespiratory system of tested people was developed. Twelve students from the university swimming combined team took part in the experiment. In the experiment were used pedagogical testing methods, biochemistry analysis of blood, cardiorespiratory indexes rating, methods of mathematical statistics. It was determined that offered methodology of hypoxic training allows to reach higher sports achievements. It is set that the use of irregular hypoxic influences is considerably modified dependence a «dose is an effect» in regard to loadings of anaerobic alactic influence

  2. Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report

    Directory of Open Access Journals (Sweden)

    Estevo Santamarina

    2015-01-01

    Conclusion: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

  3. The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity

    Science.gov (United States)

    Viollet, Benoit; Andreelli, Fabrizio; Jørgensen, Sebastian B.; Perrin, Christophe; Geloen, Alain; Flamez, Daisy; Mu, James; Lenzner, Claudia; Baud, Olivier; Bennoun, Myriam; Gomas, Emmanuel; Nicolas, Gaël; Wojtaszewski, Jørgen F.P.; Kahn, Axel; Carling, David; Schuit, Frans C.; Birnbaum, Morris J.; Richter, Erik A.; Burcelin, Rémy; Vaulont, Sophie

    2003-01-01

    AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKα2 catalytic subunit gene was inactivated. AMPKα2–/– mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKα2–/– pancreatic islets, glucose- and L-arginine–stimulated insulin secretion were not affected. AMPKα2–/– mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKα2–/– muscles. These data indicate that AMPKα2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKα2–/– mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKα2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity. PMID:12511592

  4. The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity.

    Science.gov (United States)

    Viollet, Benoit; Andreelli, Fabrizio; Jørgensen, Sebastian B; Perrin, Christophe; Geloen, Alain; Flamez, Daisy; Mu, James; Lenzner, Claudia; Baud, Olivier; Bennoun, Myriam; Gomas, Emmanuel; Nicolas, Gaël; Wojtaszewski, Jørgen F P; Kahn, Axel; Carling, David; Schuit, Frans C; Birnbaum, Morris J; Richter, Erik A; Burcelin, Rémy; Vaulont, Sophie

    2003-01-01

    AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.

  5. Control of morphology and defect density in zinc oxide for improved dye-sensitized solar cells.

    Science.gov (United States)

    Kim, Seul Ah; Abbas, Muhammad Awais; Lee, Lanlee; Kang, Byungwuk; Kim, Hahkjoon; Bang, Jin Ho

    2016-11-09

    While zinc oxide (ZnO) with a mesoporous network has long been explored for adsorption of dyes and as an electron-transporting medium in dye-sensitized solar cells (DSSCs), the performance of ZnO-based DSSCs remains unsatisfactory. Despite the importance of understanding the surface characteristics of ZnO in DSSC applications, most of the studies relevant to ZnO-based DSSCs are focused on the synthesis of unique nanostructures of ZnO. In this study, we not only introduce a novel disk-shaped ZnO nanostructure, but also provide insight into the distinctive surface properties of ZnO and its influence on DSSC performance. When utilized in DSSCs, the mesoporous ZnO nanodisk yields 60% better power conversion efficiency (PCE) compared to commercial ZnO nanoparticles, which is attributed to less surface and bulk trap densities as concluded by an in-depth open-circuit voltage decay (OCVD) analysis and electrochemical impedance spectroscopy (EIS). Another aspect that contributes to the higher PCE is the better connectivity of primary particles that join together to form secondary disk-shaped particles. Furthermore, a 40% improvement in the PCE was observed by coating the mesoporous ZnO nanodisk with TiO2, which results from the passivation of the surface defects that aid in suppressing the interfacial charge recombination.

  6. Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

    Science.gov (United States)

    Radhakrishnan, Krishnan; Cabrera, Marco

    2000-01-01

    An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

  7. Enhanced gamma ray sensitivity in bismuth triiodide sensors through volumetric defect control

    Energy Technology Data Exchange (ETDEWEB)

    Johns, Paul M.; Baciak, James E.; Nino, Juan C., E-mail: pauljohns@ufl.edu [Nuclear Engineering Program, Department of Materials Science and Engineering, University of Florida, 100 Rhines Hall, Gainesville, Florida 32611 (United States)

    2016-08-29

    Some of the more attractive semiconducting compounds for ambient temperature radiation detector applications are impacted by low charge collection efficiency due to the presence of point and volumetric defects. This has been particularly true in the case of BiI{sub 3}, which features very attractive properties (density, atomic number, band gap, etc.) to serve as a gamma ray detector, but has yet to demonstrate its full potential. We show that by applying growth techniques tailored to reduce defects, the spectral performance of this promising semiconductor can be realized. Gamma ray spectra from >100 keV source emissions are now obtained from high quality Sb:BiI{sub 3} bulk crystals with limited concentrations of defects (point and extended). The spectra acquired in these high quality crystals feature photopeaks with resolution of 2.2% at 662 keV. Infrared microscopy is used to compare the local microstructure between radiation sensitive and non-responsive crystals. This work demonstrates that BiI{sub 3} can be prepared in melt-grown detector-grade samples with superior quality and can acquire the spectra from a variety of gamma ray sources.

  8. A Wolbachia-Sensitive Communication between Male and Female Pupae Controls Gamete Compatibility in Drosophila.

    Science.gov (United States)

    Pontier, Stéphanie M; Schweisguth, François

    2015-09-21

    Gamete compatibility is fundamental to sexual reproduction. Wolbachia are maternally inherited endosymbiotic bacteria that manipulate gamete compatibility in many arthropod species. In Drosophila, the fertilization of uninfected eggs by sperm from Wolbachia-infected males often results in early developmental arrest. This gamete incompatibility is called cytoplasmic incompatibility (CI). CI is highest in young males, suggesting that Wolbachia affect sperm properties during male development. Here, we show that Wolbachia modulate testis development. Unexpectedly, this effect was associated with Wolbachia infection in females, not males. This raised the possibility that females influenced testis development by communicating with males prior to adulthood. Using a combinatorial rearing protocol, we provide evidence for such a female-to-male communication during metamorphosis. This communication involves the perception of female pheromones by male olfactory receptors. We found that this communication determines the compatibility range of sperm. Wolbachia interfere with this female-to-male communication through changes in female pheromone production. Strikingly, restoring this communication partially suppressed CI in Wolbachia-infected males. We further identified a reciprocal male-to-female communication at metamorphosis that restricts the compatibility range of female gametes. Wolbachia also perturb this communication by feminizing male pheromone production. Thus, Wolbachia broaden the compatibility range of eggs, promoting thereby the reproductive success of Wolbachia-infected females. We conclude that pheromone communication between pupae regulates gamete compatibility and is sensitive to Wolbachia in Drosophila.

  9. 吗啡缺氧预处理对兔缺氧/复氧肾脏损伤的保护作用和caspase-3的影响%Protection Against Acute Hypoxic/Reoxygenation Injury to Kidney for Rabbit with Morphine Hypoxic Preconditioning by Observing the Expression of Caspase-3 Protein

    Institute of Scientific and Technical Information of China (English)

    江晓琴; 倪娟; 杨沛; 黄蔚; 罗金凤; 李华凤; 王亚平

    2011-01-01

    The maintenance of the balance between oxygen supply and oxygen consumption is a key measure in preventing acute kidney hypoxic/reoxygenation injury. Morphine can inhibit metabolism and reduce the oxygen consumption. We tried to investigate the protective effects of morphine hypoxic preconditioning on acute kidney hypoxic/reoxygenation injury in rabbit and its influence on expression of caspase-3 protein. Kidney hypoxic and reoxy-genation were induced by making the tested rabbits inhale 8% oxygen for three hours firstly, and then putting them in the air to breathe in normal oxygen for another three hours. Morphine hypoxic preconditioning was induced by administering morphine 3mg/kg, and then hypoxic of 8% oxygen was induced. Caspase-3 protein expression in renal tissue was assessed by immunohistochemical method. In the present study, the expressions of caspase-3 protein were significantly higher in saline-control hypoxic group than in morphine hypoxic preconditioning group((29. 3±5. T)% vs. (12. 16 + 1. 23)%, P<0. 05). These observations suggested that morphine hypoxic preconditioning can protect rabbit against acute kidney hypoxic/reoxygenation injury by decreasing expression of caspase-3 protein.%维持机体氧供与氧耗相对平衡是防治缺氧/复氧损伤的重要措施.吗啡可降低代谢,降低氧耗.细胞凋亡是缺血再灌注损伤发病机制中的重要环节,半胱氨酸蛋白酶3(caspase-3)是凋亡的关键酶和执行者.本文拟通过观察缺氧/复氧损伤肾脏组织中caspase-3蛋白的变化,探讨吗啡缺氧预处理发挥肾脏保护作用的可能机制.经自制面罩吸入8% O2 3 h后吸入空气复氧3 h,建立全身缺氧/复氧肾损伤兔动物模型,缺氧/复氧结束后分别取肾脏组织,采用Envision两步法行caspase-3免疫组化染色.实验结果表明:正常对照组肾脏组织中极少的caspase-3阳性细胞表达.单纯缺氧/复氧组和吗啡缺氧预处理组阳性蛋白表达指数分别为(29.3±5

  10. Altered pain sensitivity and axioscapular muscle activity in neck pain patients compared with healthy controls

    DEFF Research Database (Denmark)

    Christensen, Steffan Wittrup; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2017-01-01

    from eight bilateral muscles. The first and last three series were separated by 8 min and 42 s, respectively. Each series consisted of three slow and three fast movements. Pressure pain thresholds (PPTs) were recorded bilaterally from neck, head and arm at baseline, after the third and sixth movement...... series. Pain intensity was recorded on an electronic visual analogue scale (VAS). RESULTS: Larger pain areas and higher VAS scores were found in patients compared with controls (p PPTs were lower in patients...

  11. Neuroinflammation and MMPs: potential therapeutic targets in neonatal hypoxic-ischemic injury

    OpenAIRE

    Pennypacker Keith R; Leonardo Christopher C

    2009-01-01

    Abstract Exposure to hypoxic-ischemic insults during the neonatal or perinatal developmental periods produces various forms of pathology. Injuries that occur in response to these events often manifest as severe cognitive and/or motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of hypoxic-ischemic injury, there is a growing need for effective therapies that can be delivered at delayed time points. Much of the research into mechanisms of neural injury...

  12. Inhibition of inflammatory mediator release from microglia can treat ischemic/hypoxic brain injury★

    OpenAIRE

    Wang, Huaibo; Guo,Weitao; Liu, Hongliang; Zeng, Rong; Lu, Mingnan; Chen, Ziqiu; Xiao, Qixian

    2013-01-01

    Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inflammatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α a...

  13. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  14. Inhibition of inflammatory mediator release from microglia can treat ischemic/hypoxic brain injury★

    OpenAIRE

    Wang, Huaibo; Guo, Weitao; Liu, Hongliang; Zeng, Rong; Lu, Mingnan; Chen, Ziqiu; Xiao, Qixian

    2013-01-01

    Interleukin-1α and interleukin-1β aggravate neuronal injury by mediating the inflammatory reaction following ischemic/hypoxic brain injury. It remains unclear whether interleukin-1α and interleukin-1β are released by microglia or astrocytes. This study prepared hippocampal slices that were subsequently subjected to oxygen and glucose deprivation. Hematoxylin-eosin staining verified that neurons exhibited hypoxic changes. Results of enzyme-linked immunosorbent assay found that interleukin-1α a...

  15. Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.

    Science.gov (United States)

    Rong, Zimei; Cooper, Chris E

    2016-01-01

    The brain responds to hypoxia with an increase in cerebral blood flow (CBF). However, such an increase is generally believed to start only after the oxygen tension decreases to a certain threshold level. Although many mechanisms (different vasodilator and different generation and metabolism mechanisms of the vasodilator) have been proposed at the molecular level, none of them has gained universal acceptance. Nitric oxide (NO) has been proposed to play a central role in the regulation of oxygen supply since it is a vasodilator whose production and metabolism are both oxygen dependent. We have used a computational model that simulates blood flow and oxygen metabolism in the brain (BRAINSIGNALS) to test mechanism by which NO may elucidate hypoxic vasodilation. The first model proposed that NO was produced by the enzyme nitric oxide synthase (NOS) and metabolized by the mitochondrial enzyme cytochrome c oxidase (CCO). NO production declined with decreasing oxygen concentration given that oxygen is a substrate for nitric oxide synthase (NOS). However, this was balanced by NO metabolism by CCO, which also declined with decreasing oxygen concentration. However, the NOS effect was dominant; the resulting model profiles of hypoxic vasodilation only approximated the experimental curves when an unfeasibly low K m for oxygen for NOS was input into the model. We therefore modified the model such that NO generation was via the nitrite reductase activity of deoxyhemoglobin instead of NOS, whilst keeping the metabolism of NO by CCO the same. NO production increased with decreasing oxygen concentration, leading to an improved reproduction of the experimental CBF versus PaO2 curve. However, the threshold phenomenon was not perfectly reproduced. In this present work, we incorporated a wider variety of oxygen dependent and independent NO production and removal mechanisms. We found that the addition of NO removal via oxidation to nitrate mediated by oxyhemoglobin resulted in the

  16. Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Takuya; Hirata, Kenji; Kobayashi, Kentaro; Manabe, Osamu; Watanabe, Shiro; Hattori, Naoya; Shiga, Tohru; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Yamaguchi, Shigeru [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Sapporo, Hokkaido (Japan); Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Neurosurgery, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Tanaka, Shinya [Hokkaido University Graduate School of Medicine, Department of Cancer Pathology, Sapporo (Japan); Ito, Yoichi M. [Hokkaido University Graduate School of Medicine, Department of Biostatistics, Sapporo (Japan)

    2017-04-15

    Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV

  17. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    OpenAIRE

    2014-01-01

    Louise Ostergaard,1,2,* Alain Rudiger,3,* Sven Wellmann,2,4,5 Elena Gammella,6 Beatrice Beck-Schimmer,2,3 Joachim Struck,7 Marco Maggiorini,2,8 Max Gassmann,1,2,9 1Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, 2Zürich Center for Integrative Human Physiology, 3Institute of Anesthesiology, 4Division of Neonatology, University Hospital Zürich, Zürich, 5Department of Neonatology, University Children's Hospital Basel, Basel...

  18. Heart rate and blood pressure responses during hypoxic cycles of a 3-week intermittent hypoxia breathing program in patients at risk for or with mild COPD.

    Science.gov (United States)

    Faulhaber, Martin; Gatterer, Hannes; Haider, Thomas; Linser, Tobias; Netzer, Nikolaus; Burtscher, Martin

    2015-01-01

    The aim of this study was to provide information on heart rate and blood pressure responses during a 3-week intermittent hypoxia breathing program in COPD patients. Sixteen participants with COPD symptoms were randomly assigned to a hypoxia or control group and completed a 3-week intermittent hypoxia breathing program (five sessions per week, each consisting of three to five breathing cycles, each cycle lasting 3-5 minutes with 3-minute breaks between cycles). During the breathing cycles, the hypoxia group received hypoxic air (inspired fraction of oxygen 15%-12%), whereas the control group received normal air (sham hypoxia). During the breaks, all participants breathed normoxic room air. Arterial oxygen saturation, systolic and diastolic blood pressure, and heart rate were measured during the normoxic and hypoxic/sham hypoxic periods. For each breathing cycle, changes from normoxia to hypoxia/sham hypoxia were calculated, and changes were averaged for each of the 15 sessions and for each week. Changes in arterial oxygen saturation were significantly different between groups in the course of the 3 weeks (two-way analysis of variance for repeated measures), with post hoc differences in weeks 1, 2, and 3. During the course of the intermittent hypoxia application, no between-group differences were detected for blood pressure or rate pressure product values. Changes in heart rate were significantly different between groups in the course of the 3 weeks (two-way analysis of variance for repeated measures), with post hoc differences only in week 3. Averages over all 15 sessions were significantly higher in the hypoxia group for heart rate and rate pressure product, and tended to be increased for systolic blood pressure. The applied intermittent hypoxia breathing program resulted in specific and moderate heart rate and blood pressure responses, and did not provoke a progressive increase in blood pressure during the hypoxic cycles in the course of the application.

  19. Emission Control in River Network System of the Taihu Basin for Water Quality Assurance of Water Environmentally Sensitive Areas

    Directory of Open Access Journals (Sweden)

    Xiao Wang

    2017-02-01

    Full Text Available As pollution incidents frequently occurred in the functional water areas of the Taihu Basin, Yangtze Delta, effective emission control to guarantee water quality in the Taihu Basin became the priority for environmental management. In this study, a new total emission control (TEC method was proposed with an emphasis on the concept of water environmentally sensitive areas (WESAs. This method was verified in Wujiang District and the techniques can be concluded in three steps: (1 a 1-D mathematical model for the study area was established and the model was calibrated using field measurement data; (2 based on an analysis of administrative planning and regulations, WESAs were identified as the main controlling objectives for emission control calculations. The weighting coefficient of local pollution sources was investigated to discuss the effectiveness of TEC on water quality improvement at WESAs; and (3 applying the river network mathematical model, water quality along the river segments was simulated under different pollution control plans. The results proved the effectiveness of TEC in the study area and indicated that a 14.6% reduction in the total amount of ammonia-nitrogen (NH3-N, as well as a 31.1% reduction in the total amount of chemical oxygen demand (CODcr, was essential in order to meet the water quality standard in the WESAs.

  20. Dynamic Control of Adsorption Sensitivity for Photo-EMF-Based Ammonia Gas Sensors Using a Wireless Network

    Directory of Open Access Journals (Sweden)

    Yuriy Vashpanov

    2011-11-01

    Full Text Available This paper proposes an adsorption sensitivity control method that uses a wireless network and illumination light intensity in a photo-electromagnetic field (EMF-based gas sensor for measurements in real time of a wide range of ammonia concentrations. The minimum measurement error for a range of ammonia concentration from 3 to 800 ppm occurs when the gas concentration magnitude corresponds with the optimal intensity of the illumination light. A simulation with LabView-engineered modules for automatic control of a new intelligent computer system was conducted to improve measurement precision over a wide range of gas concentrations. This gas sensor computer system with wireless network technology could be useful in the chemical industry for automatic detection and measurement of hazardous ammonia gas levels in real time.