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Sample records for hypoxia initial results

  1. Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results

    International Nuclear Information System (INIS)

    Wedegaertner, U.; Adam, G.; Tchirikov, M.; Schroeder, H.; Koch, M.

    2002-01-01

    Purpose: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. Material and Methods: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N 2 O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. Results: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart (∝40%) from control than in the fetal brain (∝10%). Conclusions: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow. (orig.) [de

  2. Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Wedegaertner, U.; Adam, G. [Abt. fuer Diagnostische und Interventionelle Radiologie, Klinik und Poliklinik fuer Radiologie, UKE Hamburg (Germany); Tchirikov, M.; Schroeder, H. [Abt. fuer experimentelle Gynaekologie der Universitaetsfrauenklinik, Klinik und Poliklinik fuer Frauenheilkunde, UKE, Hamburg (Germany); Koch, M. [Klinik und Poliklinik fuer Neurologie, UKE Hamburg (Germany)

    2002-06-01

    Purpose: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. Material and Methods: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N{sub 2}O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. Results: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ({proportional_to}40%) from control than in the fetal brain ({proportional_to}10%). Conclusions: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow. (orig.) [German] Ziel: Untersuchung des Potentiales der funktionellen MRT (BOLD) in der Darstellung von Veraenderungen in der Sauerstoffsaettigung fetaler Gewebe waehrend akuter materner Hypoxie bei fetalen Laemmern. Material und Methoden: Die MR-Untersuchung wurde an zwei Mutterschafen mit 125 und 131 Tage alten Feten in Inhalationsnarkose durchgefuehrt. Die BOLD Messungen von fetaler Leber, Myokard und Gehirn erfolgten waehrend einer akuten Hypoxiephase des Muttertieres, in der Sauerstoff durch N{sub 2}O ersetzt wurde. Die materne Sauerstoffsaettigung und Herzfrequenz wurde durch ein Pulsoxymeter ueberwacht. Ergebnisse: Aenderungen der fetalen Gewebsoxygenierung waehrend einer akuten Hypoxiephase der Mutter waren mit der BOLD-MR-Bildgebung deutlich darstellbar. In der fetalen Leber und dem Myokard zeigte sich ein staerkerer Signalabfall um ca. 40% von den Kontrollwerten als im fetalen

  3. NASA Gulf of Mexico Initiative Hypoxia Research

    Science.gov (United States)

    Armstrong, Curtis D.

    2012-01-01

    The Applied Science & Technology Project Office at Stennis Space Center (SSC) manages NASA's Gulf of Mexico Initiative (GOMI). Addressing short-term crises and long-term issues, GOMI participants seek to understand the environment using remote sensing, in-situ observations, laboratory analyses, field observations and computational models. New capabilities are transferred to end-users to help them make informed decisions. Some GOMI activities of interest to the hypoxia research community are highlighted.

  4. Initial results of hypoxia imaging using 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA)

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    Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N. [University of Alberta, Department of Oncology, Edmonton, Alberta (Canada); Wiebe, Leonard I. [University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta (Canada)

    2009-10-15

    Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of {sup 18}F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal {sup 18}F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of {sup 18}F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of {sup 18}F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased {sup 18}F-FAZA uptake in the primary lung tumour. No side effects of the administration of {sup 18}F-FAZA were observed. This study suggests

  5. Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

    International Nuclear Information System (INIS)

    Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N.; Wiebe, Leonard I.

    2009-01-01

    Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[ 18 F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18 F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18 F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18 F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18 F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18 F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18 F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18 F-FAZA were observed. This study suggests that 18 F-FAZA may be a very useful radiopharmaceutical

  6. Hypoxia and the initiation of erythropoietin production. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Schooley, J.C.; Mahlmann, L.J.

    1975-01-01

    The initiation of erythropoietin production in rats by hypoxia is dependent upon the magnitude of the hypoxic exposure, the position of the oxygen dissociation curve at the time of the hypoxic exposure, and the animal's endocrine status. Normal male rats produce more erythropoietin and elevate their intraerythrocytic 2,3-DPG levels more than female rats exposed to the same degree of hypoxia. Hypophysectomized rats produce erythropoietin following severe hypoxic exposure, but do not elevate their 2,3-DPG levels above control values. Respiratory acidosis in rats produced by breathing 10 percent CO/sub 2/ or by the injection of acetazolamide inhibits the initiation of erythropoietin production by hypoxic environments, but this inhibition is minimal in animals with metabolic acidosis produced by ureterligation. Changes in serum erythropoietin levels and the in vitro P/sub 50/ appear to be two separate but interrelated physiological events which occur during the adaptation of animals to hypoxic environments.

  7. The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

    Directory of Open Access Journals (Sweden)

    Roehl Anna B

    2012-08-01

    Full Text Available Abstract Backround Neuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown. Methods Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6% O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 μg kg-1 levosimendan followed by a continuous infusion of 0.2 μg kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed. Results Levosimendan reduced blood pressure during initial reperfusion (72 ± 14 vs. 109 ± 2 mmHg, p = 0.03 and delayed flow maximum by 5 minutes (p = 0.002. Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 ± 31 vs. 77 ± 8, p = 0.017 and the glutamate release during 90 minutes of reperfusion (75 ± 19 vs. 24 ± 28 μmol·L-1 were higher in the levosimendan group. The increased expression of IL-6, IL-1ß TNFα and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan. Conclusion Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood–brain barrier, the present

  8. 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

  9. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

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    Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

    2016-02-05

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

  10. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

    International Nuclear Information System (INIS)

    Tariq, Mohammad; Ito, Akihiro; Ishfaq, Muhammad; Bradshaw, Elliot; Yoshida, Minoru

    2016-01-01

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

  11. Hypoxia in Prostate Cancer: Correlation of BOLD-MRI With Pimonidazole Immunohistochemistry-Initial Observations

    International Nuclear Information System (INIS)

    Hoskin, Peter J.; Carnell, Dawn M.; Taylor, N. Jane; Smith, Rowena E.; Stirling, J. James; Daley, Frances M.; Saunders, Michele I.; Bentzen, Soren M.; Collins, David J.; D'Arcy, James A.; Padhani, Anwar P.

    2007-01-01

    Purpose: To investigate the ability of blood oxygen level-dependent (BOLD) MRI to depict clinically significant prostate tumor hypoxia. Methods and Materials: Thirty-three patients with prostate carcinoma undergoing radical prostatectomy were studied preoperatively, using gradient echo sequences without and with contrast medium enhancement, to map relative tissue oxygenation according to relaxivity rates and relative blood volume (rBV). Pimonidazole was administered preoperatively, and whole-mount sections of selected tumor-bearing slices were stained for pimonidazole fixation and tumor and nontumor localization. Histologic and imaging parameters were independently mapped onto patient prostate outlines. Using 5-mm grids, 861 nontumor grid locations were compared with 237 tumor grids (with >50% tumor per location) using contingency table analysis with respect to the ability of imaging to predict pimonidazole staining. Results: Twenty patients completed the imaging and histologic protocols. Pimonidazole staining was found in 33% of nontumor and in 70% of tumor grids. The sensitivity of the MR relaxivity parameter R 2 * in depicting tumor hypoxia was high (88%), improving with the addition of low rBV information (95%) without changing specificity (36% and 29%, respectively). High R 2 * increased the positive predictive value for hypoxia by 6% (70% to 76%); conversely, low R 2 * decreased the likelihood of hypoxia being present by 26% (70% to 44%) and by 41% (71% to 30%) when combined with rBV information. Conclusion: R 2 * maps from BOLD-MRI have high sensitivity but low specificity for defining intraprostatic tumor hypoxia. This together with the negative predictive value of 70% when combined with blood volume information makes BOLD-MRI a potential noninvasive technique for mapping prostatic tumor hypoxia

  12. Thin Air Resulting in High Pressure: Mountain Sickness and Hypoxia-Induced Pulmonary Hypertension

    Science.gov (United States)

    Richter, Manuel; Tello, Khodr; Sommer, Natascha; Gall, Henning; Ghofrani, Hossein Ardeschir

    2017-01-01

    With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body's acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research. PMID:28522921

  13. Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Milosevic, Michael F., E-mail: mike.milosevic@rmp.uhn.ca [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Townsley, Carol A. [Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Chaudary, Naz [Department of Advanced Molecular Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Clarke, Blaise [Department of Pathology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Laboratory Medicine and Pathology, University of Toronto, Toronto (Canada); Pintilie, Melania [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Fan, Stacy; Glicksman, Rachel [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Haider, Masoom [Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Imaging, University of Toronto, Toronto (Canada); Kim, Sunmo [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); MacKay, Helen [Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Medicine, University of Toronto, Toronto (Canada); Yeung, Ivan [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Hill, Richard P. [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Department of Advanced Molecular Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); and others

    2016-01-01

    Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and Materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

  14. The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity?

    Science.gov (United States)

    Mateika, Jason H; Panza, Gino; Alex, Raichel; El-Chami, Mohamad

    2017-10-31

    The following review explores the effect that intermittent or sustained hypercapnia coupled to intermittent hypoxia has on respiratory plasticity. The review explores published work which suggests that intermittent hypercapnia leads to long-term depression of respiration when administered in isolation and prevents the initiation of long-term facilitation when administered in combination with intermittent hypoxia. The review also explores the impact that sustained hypercapnia alone and in combination with intermittent hypoxia has on the magnitude of long-term facilitation. After exploring the outcomes linked to intermittent hypoxia/hypercapnia and intermittent hypoxia/sustained hypercapnia the translational relevance of the outcomes as it relates to breathing stability during sleep is addressed. The likelihood that naturally induced cycles of intermittent hypoxia, coupled to oscillations in carbon dioxide that range between hypocapnia and hypercapnia, do not initiate long-term facilitation is addressed. Moreover, the conditions under which intermittent hypoxia/sustained hypercapnia could serve to improve breathing stability and mitigate co-morbidities associated with sleep apnea are considered. Published by Elsevier B.V.

  15. Hypofractionation results in reduced tumor cell kill compared to conventional fractionation for tumors with regions of hypoxia.

    Science.gov (United States)

    Carlson, David J; Keall, Paul J; Loo, Billy W; Chen, Zhe J; Brown, J Martin

    2011-03-15

    Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10(5) over a distance of 130 μm. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of ∼10(3) as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking

    Science.gov (United States)

    Li, Jian; Zucker, Stanley; Pulkoski-Gross, Ashleigh; Kuscu, Cem; Karaayvaz, Mihriban; Ju, Jingfang; Yao, Herui; Song, Erwei; Cao, Jian

    2012-01-01

    Emerging evidence has implicated the role of tumor initiating cells (TICs) in the process of cancer metastasis. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. In this report, we employed less invasive breast cancer TICs, SK-3rd, that displays CD44high/CD24low with high mammosphere-forming and tumorigenic capacities, to investigate the mechanism by which stationary TICs are converted to invasive TICs. Invasive ability of SK-3rd TICs was markedly enhanced when the cells were cultured under hypoxic conditions. Given the role of membrane type 1-matrix metalloproteinase (MT1-MMP) in cancer invasion/metastasis, we explored a possible involvement of MT1-MMP in hypoxia-induced TIC invasion. Silencing of MT1-MMP by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. Under hypoxic conditions, MT1-MMP redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MT1-MMP. Interestingly, cell surface MT1-MMP gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MT1-MMP in cytoplasmic storage pools under normoxic conditions, by demonstrating a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MT1-MMP expression in SK-3rd TICs. These observations suggest that MT1-MMP is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis. PMID:22679501

  17. Aquarius: The Instrument and Initial Results

    Science.gov (United States)

    Vine, David M Le; Lagerloef, G.S.E.; Ruf, C.; Wentz, F.; Yueh, S.; Piepmeier, J.; Lindstrom, E.; Dinnat, E.

    2012-01-01

    Aquarius was launched on June 10, 2011 aboard the Aquarius/SAC-D observatory and the instrument has been operating continuously since the initial turned-on was completed on August 25. The initial observed antenna temperatures were close to predicted and the first salinity map was released in September. In order to map the ocean salinity field, Aquarius includes several special features such as the inclusion of a scatterometer to provide a roughness correction, measurement of the third Stokes parameter to correct for Faraday rotation, and fast sampling to mitigate the effects of RFI. This paper provides an overview of the instrument and an example of initial results. Details are covered in subsequent papers in the session on Aquarius

  18. Regulation of mRNA translation influences hypoxia tolerance

    International Nuclear Information System (INIS)

    Koritzinsky, M.; Wouters, B.G.; Koumenis, C.

    2003-01-01

    Hypoxia is a heterogenous but common characteristic of human tumours and poor oxygenation is associated with poor prognosis. We believe that the presence of viable hypoxic tumor cells reflects in part an adaptation and tolerance of these cells to oxygen deficiency. Since oxidative phosphorylation is compromized during hypoxia, adaptation may involve both the upregulation of glycolysis as well as downregulation of energy consumption. mRNA translation is one of the most energy costly cellular processes, and we and others have shown that global mRNA translation is rapidly inhibited during hypoxia. However, some mRNAs, including those coding for HIF-1 α and VEGF, remain efficiently translated during hypoxia. Clearly, the mechanisms responsible for the overall inhibition of translation during hypoxia does not compromize the translation of certain hypoxia-induced mRNA species. We therefore hypothesize that the inhibition of mRNA translation serves to promote hypoxia tolerance in two ways: i) through conservation of energy and ii) through differential gene expression involved in hypoxia adaptation. We have recently identified two pathways that are responsible for the global inhibition of translation during hypoxia. The phosphorylation of the eukaryotic initiation factor eIF2 α by the ER resident kinase PERK results in down-regulation of protein synthesis shortly after the onset of hypoxia. In addition, the initiation complex eIF4F is disrupted during long lasting hypoxic conditions. The identification of the molecular pathways responsible for the inhibition of overall translation during hypoxia has rendered it possible to investigate their importance for hypoxia tolerance. We have found that mouse embryo fibroblasts that are knockout for PERK and therefore not able to inhibit protein synthesis efficiently during oxygen deficiency are significantly less tolerant to hypoxia than their wildtype counterparts. We are currently also investigating the functional significance

  19. Care initiation area yields dramatic results.

    Science.gov (United States)

    2009-03-01

    The ED at Gaston Memorial Hospital in Gastonia, NC, has achieved dramatic results in key department metrics with a Care Initiation Area (CIA) and a physician in triage. Here's how the ED arrived at this winning solution: Leadership was trained in and implemented the Kaizen method, which eliminates redundant or inefficient process steps. Simulation software helped determine additional space needed by analyzing arrival patterns and other key data. After only two days of meetings, new ideas were implemented and tested.

  20. Preeclampsia, Hypoxia, Thrombosis, and Inflammation

    Directory of Open Access Journals (Sweden)

    Amir A. Shamshirsaz

    2012-01-01

    Full Text Available Reductions in uteroplacental flow initiate a cascade of molecular effects leading to hypoxia, thrombosis, inflammation, and endothelial cell dysfunction resulting in untoward pregnancy outcomes. In this review, we detail these effects and their relationship to preeclampsia (PE and intrauterine growth restriction (IUGR.

  1. Overview of the initial NSTX experimental results

    International Nuclear Information System (INIS)

    Ono, M.; Bell, M.G.; Bell, R.E.

    2001-01-01

    The main aim of the National Spherical Torus Experiment (NSTX) is to establish the fusion physics principles of the spherical torus (ST) concept. The NSTX device began plasma operations in February 1999 and the plasma current I p was successfully brought up to the design value of 1 MA on 14 December 1999. The planned plasma shaping parameters, elongation κ=1:6-2.2 and triangularity δ=0:2-0.4, were achieved in inner wall limited, and single null and double null diverted configurations. The coaxial helicity injection (CHI) and high harmonic fast wave (HHFW) experiments were also initiated. CHI current of 27 kA produced up to 260 kA toroidal current without using an ohmic solenoid. With the injection of 2.3 MW of HHFW power, using 12 antennas connected to six transmitters, electrons were heated from a central temperature of 400 eV to 900 eV at a central density of 3.5x10 13 cm 3 , increasing the plasma energy to 59 kJ and the toroidal β, β T , to 10%. The NBI system commenced operation in September 2000. The initial results with two ion sources (P NBI =2:8 MW) show good heating, producing a total plasma stored energy of 90 kJ corresponding to β T ∼18% at a plasma current of 1.1 MA. (author)

  2. Overview of the initial NSTX experimental results

    International Nuclear Information System (INIS)

    Ono, M.; Bell, M.; Bell, R.

    2001-01-01

    The main aim of the National Spherical Torus Experiment (NSTX) is to establish the fusion physics principles of the spherical torus (ST) concept. The NSTX device began plasma operations in February 1999 and the plasma current I p was successfully brought up to the design value of 1 million amperes on December 14, 1999. The planned plasma shaping parameters, κ=1.6-2.2 and δ=0.2-0.4, were achieved in inner limited, single null and double null configurations. The CHI (Coaxial Helicity Injection) and HHFW (High Harmonic Fast Wave) experiments were also initiated. A CHI injected current of 27 kA produced up to 260 kA of toroidal current without using an ohmic solenoid. With an injection of 2.3 MW of HHFW power, using twelve antennas connected to six transmitters, electrons were heated from a central temperature of 400 eV to 900 eV at a central density of 3.5x10 13 cm -3 increasing the plasma energy to 59 kJ and the toroidal beta, β T to 10 %. Finally, the NBI system commenced operation in Sept. 2000. The initial results with two ion sources (P NBI =2.8MW) shows good heating, producing a total plasma stored energy of 90 kJ corresponding to β T ∼18% at a plasma current of 1.1 MA. (author)

  3. Overview of the Initial NSTX Experimental Results

    International Nuclear Information System (INIS)

    Ono, M.; Bell, M.; Bell, R. E.; Bigelow, T.; Bitter, M.

    2000-01-01

    The main aim of the National Spherical Torus Experiment (NSTX) is to establish the fusion physics principles of the spherical torus (ST) concept. The NSTX device began plasma operations in February 1999 and the plasma current Ip was successfully brought up to the design value of 1 million amperes on December 14, 1999. The planned plasma shaping parameters, k = 1.6 ± 2.2 and d = 0.2 ± 0.4, were achieved in inner limited, single null and double null configurations. The CHI (Coaxial Helicity Injection) and HHFW (High Harmonic Fast Wave) experiments were also initiated. A CHI injected current of 27 kA produced up to 260 kA of toroidal current without using an ohmic solenoid. With an injection of 2.3 MW of HHFW power, using twelve antennas connected to six transmitters, electrons were heated from a central temperature of 400 eV to 900 eV at a central density of 3.5 x 1013 cm-3 increasing the plasma energy to 59 kJ and the toroidal beta, bT to 10 %. Finally, the NBI system commenced operation in Sept. 2000. The initial results with two ion sources (PNBI = 2.8 MW) shows good heating, producing a total plasma stored energy of 90 kJ corresponding to bT = 18 % at a plasma current of 1.1 MA

  4. Angiographic assessment of initial balloon angioplasty results.

    Science.gov (United States)

    Gardiner, Geoffrey A; Sullivan, Kevin L; Halpern, Ethan J; Parker, Laurence; Beck, Margaret; Bonn, Joseph; Levin, David C

    2004-10-01

    To determine the influence of three factors involved in the angiographic assessment of balloon angioplasty-interobserver variability, operator bias, and the definition used to determine success-on the primary (technical) results of angioplasty in the peripheral arteries. Percent stenosis in 107 lesions in lower-extremity arteries was graded by three independent, experienced vascular radiologists ("observers") before and after balloon angioplasty and their estimates were compared with the initial interpretations reported by the physician performing the procedure ("operator") and an automated quantitative computer analysis. Observer variability was measured with use of intraclass correlation coefficients and SD. Differences among the operator, observers, and the computer were analyzed with use of the Wilcoxon signed-rank test and analysis of variance. For each evaluator, the results in this series of lesions were interpreted with three different definitions of success. Estimation of residual stenosis varied by an average range of 22.76% with an average SD of 8.99. The intraclass correlation coefficients averaged 0.59 for residual stenosis after angioplasty for the three observers but decreased to 0.36 when the operator was included as the fourth evaluator. There was good to very good agreement among the three independent observers and the computer, but poor correlation with the operator (P definition of success was used. Significant differences among the operator, the three observers, and the computer were not present when the definition of success was based on less than 50% residual stenosis. Observer variability and bias in the subjective evaluation of peripheral angioplasty can have a significant influence on the reported initial success rates. This effect can be largely eliminated with the use of residual stenosis of less than 50% to define success. Otherwise, meaningful evaluation of angioplasty results will require independent panels of evaluators or

  5. Homestake surface-underground scintillators: Initial results

    International Nuclear Information System (INIS)

    Cherry, M.L.; Corbato, S.; Daily, T.; Fenyves, E.J.; Kieda, D.; Lande, K.; Lee, C.K.

    1986-01-01

    The first 70 tons of the 140-ton Large Area Scintillation Detector (LASD) have been operating since Jan. 1985 at a depth of 4850 ft. (4200 m.w.e.) in the Homestake Gold Mine, Lead, S.D. A total of 4 x 10(4) high-energy muons (E sub mu is approx. 2.7 TeV at the surface) have been detected. The remainder of the detector is scheduled to be in operation by the Fall of 1985. In addition, a surface air shower array is under construction. The first 27 surface counters, spaced out over an area of 270' x 500', began running in June, 1985. The LASD performance, the potential of the combined shower array and underground muon experiment for detecting point sources, and the initial results of a search for periodic emission from Cygnus X-3 are discussed

  6. Initial results from MARmara SuperSITE

    Science.gov (United States)

    Meral Ozel, Nurcan; Necmioglu, Ocal; Favali, Paolo; Douglas, John; Mathieu, Pierre-Philippe; Geli, Louis; Ergintav, Semih; Oguz Ozel, Asım; Tan, Onur; Gurbuz, Cemil; Erdik, Mustafa

    2014-05-01

    MARSite Project was initiated in November 2012 under the EC/FP-7 framework as an initiative towards establishment of new directions in seismic hazard assessment through focused earth observation in Marmara Region. Within MARSite, collection of the first comprehensive data set of fluids composition around the Sea of Marmara has been accomplished and first insight in the geochemical features of the fluids are expelled from tectonic structures around the Sea of Marmara. GPS time series and velocity fields are periodically updated and a project proposal has been prepared for Supersite initiative to take SAR data and integrate the results with in-situ data sets, which is accepted by the scientific committee of GEOSS. In the meantime, special focus was given to develop the processing algorithms, starting from low level atmospheric correction to high level modeling routines. Considerable progress has been made in the novel design of a multiparameter borehole system consisting of very wide dynamic range and stable borehole (VBB) broad band seismic sensor also incorporating 3-D strain meter, tilt meter, and temperature and local hydrostatic pressure measuring devices. Borehole and surface array locations and borehole bedrock depth of 137 m has been identified. A modeling scheme for the scenario earthquake simulation has been set up in order to realize processing of real-time high-rate GPS data and simulating of scenario earthquakes. The probability of occurrence for the fault segmentation in the Marmara region were calculated using the Poisson, BPT and BPT with a stress interaction models for time intervals of 5-10-30 and 50 years. High resolution seismic reflection and multibeam data in the easternmost Cinarcik basin obtained during the cruise MARMARA 2013 carried out onboard the CNR R/V Urania ship provided information on diffuse gravitational failures. An in situ multi-parameter observational system for landslide monitoring, including displacement, rainfall and seismic

  7. Initial results from the RHEPP module

    International Nuclear Information System (INIS)

    Harjes, H.C.; Penn, K.J.; Reed, K.W.; McClenahan, C.R.; Laderach, G.E.; Wavrik, R.W.; Adcock, J.L.; Butler, M.E.; Mann, G.A.; Pena, G.E.

    1993-01-01

    Several potential applications such as medical waste treatment, chemical waste treatment, food treatment, and flue gas cleanup have been identified for high average power electron beam systems. In the RHEPP (Repetitive High Energy Pulsed Power) project, the technology for such a system is being developed. The RHEPP module consists of a magnetic pulse compressor driving a linear induction voltage adder with an e-beam diode load. It has been designed to operate continuously, delivering 350 kW of average power to the diode in 60-ns FWHM, 2.5-MV, 2.9-kJ pulses. The module is presently under construction with the first phase scheduled for completion in the summer of 1992. In the first phase, four of ten adder stages are being built so that testing can begin with a 1-MV, 160-kW diode with the balance of the power from the compressor diverted to a resistive load. A description of the system and test results from the initial stages of the compressor will be presented

  8. Intermittent hypoxia initiated plasticity in humans: A multipronged therapeutic approach to treat sleep apnea and overlapping co-morbidities.

    Science.gov (United States)

    Mateika, Jason H; Komnenov, Dragana

    2017-01-01

    Over the past three decades exposure to intermittent hypoxia (IH) has generally been considered a stimulus associated with a number of detrimental outcomes. However, there is sufficient evidence to link IH to many beneficial outcomes but they have largely been ignored, particularly in the field of sleep medicine in the United States. Recent reviews have postulated that this apparent contradiction is related to the severity and duration of exposure to IH; mild forms of IH initiate beneficial outcomes while severe forms of IH are coupled to detrimental consequences. In the present review we explore the role that IH has in initiating respiratory plasticity and the potential this form of plasticity has to mitigate obstructive sleep apnea (OSA) in humans. In taking this approach, we address the possibility that IH could serve as an adjunct therapy coupled with continuous positive airway pressure (CPAP) to treat OSA. Our working hypothesis is that exposure to mild IH leads to respiratory plasticity that manifests in increased stability of the upper airway, which could ultimately reduce the CPAP required to treat OSA. In turn, this reduction could increase CPAP compliance and extend the length of treatment each night, which might improve the magnitude of outcome measures. Improved treatment compliance coupled with the direct effect that IH has on numerous overlapping conditions (i.e. asthma, chronic obstructive pulmonary disease, spinal cord injury) may well lead to substantial improvements that exceed outcomes following treatment with CPAP alone. Overall, this review will consider evidence from the published literature which suggests that IH could serve as an effective multipronged therapeutic approach to treat sleep apnea and its overlapping co-morbidities. Published by Elsevier Inc.

  9. Initial Results from the Kwajalein Micrometeorite Collections

    Science.gov (United States)

    Wozniakiewicz, P. J.; Bradley, J. P.; Price, M. C.; Zolensky, M. E.; Ishii, H. A.; Brownlee, D. E.; Dearborn, D.; Jones, T.; Barnett, B.; Yakuma, S.; hide

    2014-01-01

    Micrometeorites are constantly arriving at the Earth's surface, however, they are quickly diluted by the natural and anthropogenic back-ground dust. The successful collection of micromete-orites requires either the employment of a separation technique (e.g. using magnets to separate metal-bearing micrometeorites from deepsea sediments [e.g. 1,2] and dissolved pre-historic limestones and salts [e.g. 3,4]), or an approach that limits contamination by terrestrial dust (e.g. collecting from ice, snow and well water in polar regions - locations where the terrestrial dust flux is so low that micrometeorites repre-sent the major dust component [e.g. 5-7]). We have recently set up a micrometeorite collection station on Kwajalein Island in the Republic of the Marshall Is-lands in the Pacific Ocean, using high volume air samplers to collect particles directly from the atmosphere. Collecting at this location exploits the considerably reduced anthropogenic background; Kwajalein is >1000 miles from the nearest continent and for much of the year, trade winds blow from the northeast at 15 to 20 knots providing a continuous stream of oceanic aerosol for sampling. By collecting directly from the atmosphere, the terrestrial age of the particles, and hence weathering they experience, is minimal. We therefore anticipate that the Kwajalein col-lection may include particles that are highly susceptible to weathering and either not preserved well or not found at all in other collections. In addition, this collection method allows for particle arrival times to be constrained so that collections can be timed to correlate with celestial events (e.g. meteor showers). Here we describe the collections and their preparation and report on the initial results.

  10. Th17 Polarization under Hypoxia Results in Increased IL-10 Production in a Pathogen-Independent Manner

    Directory of Open Access Journals (Sweden)

    Roman Volchenkov

    2017-06-01

    Full Text Available The IL-17-producing CD4+ T helper cell (Th17 differentiation is affected by stimulation of the aryl hydrocarbon receptor (AhR pathway and by hypoxia-inducible factor 1 alpha (HIF-1α. In some cases, Th17 become non-pathogenic and produce IL-10. However, the initiating events triggering this phenotype are yet to be fully understood. Here, we show that such cells may be differentiated at low oxygen and regardless of AhR ligand treatment such as cigarette smoke extract. Hypoxia led to marked alterations of the transcriptome of IL-10-producing Th17 cells affecting genes involved in metabolic, anti-apoptotic, cell cycle, and T cell functional pathways. Moreover, we show that oxygen regulates the expression of CD52, which is a cell surface protein that has been shown to suppress the activation of other T cells upon release. Taken together, these findings suggest a novel ability for Th17 cells to regulate immune responses in vivo in an oxygen-dependent fashion.

  11. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2013-01-01

    Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

  12. Hypoxia symptoms during altitude training in professional Iranian fighter pilots.

    Science.gov (United States)

    Alagha, Babak; AhmadBeygi, Shervin; Ahmadbeigy, Shervin; Moosavi, Seyed Ali Javad; Jalali, Seyed Mahmood

    2012-01-01

    Susceptibility to hypoxia is influenced by a multitude of factors, including fatigue, physical activity, illnesses, ambient temperature, rate of ascent, destination altitude, medications, and alcohol. Anecdotally, several reports have been made regarding changes in the form of hypoxia presentation in Iranian fighter pilots in the absence of these factors. This study focused specifically on the effect of pilot age on susceptibility to hypoxia and its initial presentation. We assumed that a pilot's age may increase his susceptibility to hypoxia and consequently reduce the amount of time it takes for hypoxia to present. Because our literature review did not reveal any previous study addressing the possible relationship between age and susceptibility to hypoxia, the purpose of this study is to address and clarify this relationship. In this retrospective study, we collected information from Iranian fighter pilots (n = 30) through an anonymous questionnaire in 2000. The form of hypoxia presentation of each subject was evaluated during five altitude chamber training (ACT) sessions that were conducted routinely from 1972 to 1984. To enhance the accuracy of the study's results, confounding factors such as prior hypoxia experience in an ACT session have been taken into consideration. The results revealed a statistically significant relationship between age and a change in the form of hypoxia presentation in our subjects. Increased age reduced the amount of time before the first individual hypoxia symptom appeared (P < .000002). Although having previous hypoxia experience may help pilots to recognize their symptoms earlier, its effect was not statistically significant (P < .18). A few changes in the nature of individual symptoms were observed; however, we did not find a meaningful statistical correlation between pilot age and change in the nature of symptoms. Susceptibility ot hypoxia increases with pilot age. Copyright © 2012 Air Medical Journal Associates. Published by

  13. Hypoxia Room

    Data.gov (United States)

    Federal Laboratory Consortium — The Hypoxia Room is a 8x8x8 ft. clear vinyl plastic and aluminum frame construction enclosure located within USAREIM laboratory 028. The Hypoxia Room (manufactured...

  14. Arase: mission overview and initial results

    Science.gov (United States)

    Miyoshi, Y.; Shinohara, I.; Takashima, T.; Asamura, K.; Wang, S. Y.; Kazama, Y.; Kasahara, S.; Yokota, S.; Mitani, T.; Higashio, N.; Kasahara, Y.; Kasaba, Y.; Yagitani, S.; Matsuoka, A.; Kojima, H.; Kazuo, S.; Seki, K.; Hori, T.; Shoji, M.; Teramoto, M.; Chang, T. F.; Kurita, S.; Matsuda, S.; Keika, K.; Miyashita, Y.; Hosokawa, K.; Ogawa, Y.; Kadokura, A.; Kataoka, R.; Ono, T.

    2017-12-01

    Geospace Exploation Project; ERG addresses what mechanisms cause acceleration, transportation and loss of MeV electrons of the radiation belts and evolutions of space storms. Cross-energy and cross-regional couplings are key concepts for the project. In order to address questions, the project has been organized by three research teams; satellite observations, ground-based observations, and modeling/data-analysis studies, and interdisciplinary research are realized for comprehensive understanding of geospace. The Arase (ERG) satellite had been developed and 9 science instruments are developed and provided from JAXA, universities and instituted in Japan and Taiwan. The Arase satellite was successfully launched on December 20, 2016. After the initial operation including maneuvers, Arase has started normal observations since March, 2017. Until now, Arase has observed several geomagnetic storms driven by coronal hole streams and CMEs, and several interesting features are observed associated with geomagnetic disturbances. The six particle instruments; LEP-e/LEP-i/MEP-e/MEP-i/HEP/XEP have shown large enhancement as well as loss of wide energy electrons and ions and variations as well as changes of pitch angle and energy spectrum. The two field/wave instruments: PWE and MGF observed several kinds of plasma waves such as chorus, hiss, EMIC as well as large scale electric and magnetic field variations. And newly developed S-WPIA has been operated to identify micro-process of wave-particle interactions. Since conjugate observations between Arase and ground-based observations are essential for comprehensive understanding of geospace, we organized several campaign observations that include both satellite and ground-based observations. The project has collaborated with the international projects, EISCAT, SuperDARN and other ground-based observations, and various data are obtained from such international collaborations. Moreover, multi-point satellite observations by

  15. REXEBTS, design and initial commissioning results

    CERN Document Server

    Wenander, F; Jonson, B; Liljeby, L; Nyman, G H; Rensfelt, K G; Skeppstedt, Ö; Wolf, B

    2001-01-01

    The REXEDIS is an Electron Beam Ion Source (EBIS) developed particularly for charge breeding of rare and short-lived isotopes produced at ISOLDE for the REX-ISOLDE post accelerator. Bunches of singly charged radioactive ions are injected into the EBIS and charge bred to a charge-to-mass ratio of approximately 1/4 and thereafter extracted and injected into a short LINAC. This novel concept, employing a Penning trap to bunch and cool the ions from an on-line mass separator prior to charge breeding in an EBIS, results in an efficient and compact system. In this article the final REXEBIS design is presented together with results from the first tests. (19 refs).

  16. Fetal exposure to a diabetic intrauterine environment resulted in a failure of cord blood endothelial progenitor cell adaptation against chronic hypoxia

    Directory of Open Access Journals (Sweden)

    Dincer UD

    2014-12-01

    Full Text Available U Deniz Dincer Department of Basic and Clinical Pharmacology, School of Medicine, Bezmialem Vakif University (BAVU, Fatih/Istanbul, Turkey Abstract: Gestational diabetes mellitus (GDM has long-term health consequences, and fetal exposure to a diabetic intrauterine environment increases cardiovascular risk for her adult offspring. Some part of this could be related to their endothelial progenitor cells (EPCs. Understanding the vessel-forming ability of human umbilical cord blood (HUCB-derived endothelial colony-forming cells (ECFCs against pathological stress such as GDM response to hypoxia could generate new therapeutic strategies. This study aims to investigate the role of chronic hypoxia in EPCs functional and vessel-forming ability in GDM subjects. Each ECFC was expressed in endothelial and pro-angiogenic specific markers, namely endothelial nitric oxide synthase (eNOS, platelet (PECAM-1 endothelial cell adhesion molecule 1, vascular endothelial-cadherin CdH5 (Ca-dependent cell adhesion molecule, vascular endothelial growth factor A, (VEGFA and insulin-like growth factor 1 (IGF1. Chronic hypoxia did not affect CdH5, but PECAM1 MRNA expressions were increased in control and GDM subjects. Control hypoxic and GDM normoxic VEGFA MRNA expressions and hypoxia-inducible factor 1-alpha (HIF1α protein expressions were significantly increased in HUCB ECFCs. GDM resulted in most failure of HUCB ECFC adaptation and eNOS protein expressions against chronic hypoxia. Chronic hypoxia resulted in an overall decline in HUCB ECFCs' proliferative ability due to reduction of clonogenic capacity and diminished vessel formation. Furthermore, GDM also resulted in most failure of cord blood ECFC adaptation against chronic hypoxic environment. Keywords: endothelial progenitor cells, gestational diabetes mellitus, chronic hypoxia, human cord blood

  17. ERNIE performance with TSA portals Initial Results

    Energy Technology Data Exchange (ETDEWEB)

    Labov, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2018-01-05

    This project extends the “Enhanced Radiological Nuclear Inspection and Evaluation” (ERNIE) system developed with CBP and DNDO to improve performance of PVT-based Radiation Portal Monitors (RPMs). ERNIE was designed to be used with any RPM system. The first implementation was with the SAIC (Leidos) RPM-8 systems. In this project, we are demonstrating how effective the ERNIE approach can be when applied to the VM250 TSA portals used in NSDD programs. Part of the challenge in adapting ERNIE to handle VM250 portals is the lack of gamma spectral information. We report here on the first results showing how the ERNIE analysis can improve analysis of measurements with the VM250 RPMs.

  18. Breast tomosynthesis in clinical practice: initial results

    International Nuclear Information System (INIS)

    Teertstra, Hendrik J.; Loo, Claudette E.; Bosch, Maurice A.A.J. van den; Muller, Sara H.; Gilhuijs, Kenneth G.A.; Tinteren, Harm van; Rutgers, Emiel J.T.

    2010-01-01

    The purpose of this study was to assess the potential value of tomosynthesis in women with an abnormal screening mammogram or with clinical symptoms. Mammography and tomosynthesis investigations of 513 woman with an abnormal screening mammogram or with clinical symptoms were prospectively classified according to the ACR BI-RADS criteria. Sensitivity and specificity of both techniques for the detection of cancer were calculated. In 112 newly detected cancers, tomosynthesis and mammography were each false-negative in 8 cases (7%). In the false-negative mammography cases, the tumor was detected with ultrasound (n=4), MRI (n=2), by recall after breast tomosynthesis interpretation (n=1), and after prophylactic mastectomy (n=1). Combining the results of mammography and tomosynthesis detected 109 cancers. Therefore in three patients, both mammography and tomosynthesis missed the carcinoma. The sensitivity of both techniques for the detection of breast cancer was 92.9%, and the specificity of mammography and tomosynthesis was 86.1 and 84.4%, respectively. Tomosynthesis can be used as an additional technique to mammography in patients referred with an abnormal screening mammogram or with clinical symptoms. Additional lesions detected by tomosynthesis, however, are also likely to be detected by other techniques used in the clinical work-up of these patients. (orig.)

  19. Transcription factor HIF1A: downstream targets, associated pathways, polymorphic hypoxia response element (HRE) sites, and initiative for standardization of reporting in scientific literature.

    Science.gov (United States)

    Slemc, Lucija; Kunej, Tanja

    2016-11-01

    Hypoxia-inducible factor-1α (HIF-1α) has crucial role in adapting cells to hypoxia through expression regulation of many genes. Identification of HIF-1α target genes (HIF-1α-TGs) is important for understanding the adapting mechanism. The aim of the present study was to collect known HIF-1α-TGs and identify their associated pathways. Targets and associated genomics data were retrieved using PubMed, WoS ( http://apps.webofknowledge.com/ ), HGNC ( http://www.genenames.org/ ), NCBI ( http://www.ncbi.nlm.nih.gov/ ), Ensemblv.84 ( http://www.ensembl.org/index.html ), DAVID Bioinformatics Resources ( https://david.ncifcrf.gov /), and Disease Ontology database ( http://disease-ontology.org/ ). From 51 papers, we collected 98 HIF-1α TGs found to be associated with 20 pathways, including metabolism of carbohydrates and pathways in cancer. Reanalysis of genomic coordinates of published HREs (hypoxia response elements) revealed six polymorphisms within HRE sites (HRE-SNPs): ABCG2, ACE, CA9, and CP. Due to large heterogeneity of results presentation in scientific literature, we also propose a first step towards reporting standardization of HIF-1α-target interactions consisting of ten relevant data types. Suggested minimal checklist for reporting will enable faster development of a complete catalog of HIF-1α-TGs, data sharing, bioinformatics analyses, and setting novel more targeted hypotheses. The proposed format for data standardization is not yet complete but presents a baseline for further optimization of the protocol with additional details, for example, regarding the experimental validation.

  20. Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: informed scheduling of the bioreductive drug AQ4N improves treatment response.

    Science.gov (United States)

    Ming, Louise; Byrne, Niall M; Camac, Sarah Nicole; Mitchell, Christopher A; Ward, Claire; Waugh, David J; McKeown, Stephanie R; Worthington, Jenny

    2013-03-15

    Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide-treated and vehicle-only-treated tumours were re-established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 ± 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit. Copyright © 2012 UICC.

  1. Exercise performed at hypoxia influences mood state and anxiety symptoms

    Directory of Open Access Journals (Sweden)

    Jorge Fernando Tavares de Souza

    2015-06-01

    Full Text Available During hypoxia conditions, psychological states can be worsened. However, little information is available regarding the effect of physical exercise performed in hypoxia conditions on mood state and anxiety symptoms. The aim of the present study was to elucidate the acute effect of moderate physical exercise performed at hypoxia on mood states and anxiety symptoms in healthy young subjects. Ten volunteers were subjected to the following conditions: a normoxic condition (NC and a hypoxic condition (HC. They performed 45 min of physical exercise. Their anxiety symptoms and mood states were evaluated at the initial time point as well as immediately following and 30 and 60 min after the exercise session. Our results showed a significant increase in post-exercise anxiety symptoms and a significant decrease in mood scores immediately after and 30 min after exercise performed in the HC. Moderate physical activity performed at hypoxia condition increased post-exercise anxiety and worsened mood state.

  2. Hypoxia targeting copper complexes

    International Nuclear Information System (INIS)

    Dearling, J.L.

    1998-11-01

    selectivity increasing with decreasing reduction potential. A mechanism accounting for the observed results is suggested. A brief survey of the selectivities of other copper complexing ligands (dithiocarbamates, diphosphines and Schiff-bases) is presented, though neither normoxic nor hypoxic selectivity was found. In conclusion a structure-activity relationship exists within this series, and it is possible using these observations to design hypoxia selective copper complexes rationally. (author)

  3. Initial results from the Tokapole-II poloidal divertor device

    International Nuclear Information System (INIS)

    Biddle, A.P.; Dexter, R.N.; Groebner, R.J.; Holly, D.J.; Lipschultz, B.; Phillips, M.W.; Prager, S.C.; Sprott, J.C.

    1979-01-01

    The latest in a series of internal-ring devices, called Tokapole II, has recently begun operation at the University of Wisconsin. Its purpose is to permit the study of the production and confinement of hot, dense plasmas in either a toroidal octupole (with or without toroidal field) or a tokamak with a four-node poloidal divertor. The characteristics of the device and the results of its initial operation are described here. Quantitative measurements of impurity concentration and radiated power have been made. Poloidal divertor equilibria of square and dee shapes have been produced, and an axisymmetric instability has been observed with the inverse dee. Electron cyclotron resonance heating is used to initiate the breakdown near the axis and to control the initial influx of impurities. A 2-MW RF source at the second harmonic of the ion cyclotron frequency is available and has been used to double the ion temperature when operated at low power with an unoptimized antenna. Initial results of operation as a pure octupole with poloidal Ohmic heating suggest a tokamak-like scaling of density (n proportional to Bsub(p)) and confinement time (tau proportional to n). (author)

  4. Do corporate environmental initiatives lead to results in SMEs?

    DEFF Research Database (Denmark)

    Madsen, Henning; Ulhøi, John Parm

    , it is relevant to study the situation between these two stages in order to identify to which extent corporate environmental initiatives actually lead to results and reductions. The research is based on data collected by surveys of industrial companies in Denmark in 1999, 2003, 2007 and 2011. They information...... with previous research demonstrating that companies generally are re-active in their attitude when perceiving stakeholder influence on taking environmental initiative and mainly respond to influence from stakeholders representing authorities, owners or employees. However, the size of the company may have...... a negative influence in some situations. That is, it seems to be easier for smaller companies to achieve an improvement compared to medium-sized companies....

  5. Cabo Verde telemedicine program: initial results of nationwide implementation.

    Science.gov (United States)

    Latifi, Rifat; Dasho, Erion; Merrell, Ronald C; Lopes, Miguel; Azevedo, Vanda; Bekteshi, Flamur; Osmani, Kalterina L; Qesteri, Orland; Kucani, Julian; Lecaj, Ismet

    2014-11-01

    Telemedicine and e-health have been suggested as one solution for closing the health disparity gap between the developed world and the developing world. Yet evidence is lacking from current successful programs in the developing world and, in particular, from sub-Saharan Africa. The primary objective of our study was to present the preliminary results of our efforts in building the Integrated Telemedicine and e-Health Program for Cabo Verde (ITeHP-CV), with an emphasis on initial utilization and results. This is a prospective study of data collected while we worked to establish a fully functional, integrated national telemedicine network and virtual education network in Cabo Verde. We used the International Virtual e-Hospital Foundation strategic approach known as "initiate-build-operate-transfer" over a 26-month period (November 2011-December 2013). We describe herein the five main pillars of this process that have been implemented: (1) capacity building; (2) network development and deployment of equipment; (3) implementation of clinical telemedicine; (4) implementation of activities related to continuing medical education, delivered from within the country and from abroad; and (5) establishment and use of the electronic virtual library. Based on comprehensive technical and medical assessment of the country's needs, 10 fully functional telemedicine centers in all nine inhabited islands of the Republic of Cabo Verde have been established. RESULTS are presented under the five main pillars of capacity building, network deployment, implementation of clinical telemedicine, implementation of continuing medical education activities, and establishment of the electronic virtual library. The ITeHP-CV has been successfully launched, and the initial results are encouraging. The continuity of the program and sustainability are primary goals once the program is transferred fully to the Ministry of Health of Cabo Verde. A long-term follow-up study is required in order to ensure

  6. Coastal hypoxia and sediment biogeochemistry

    Directory of Open Access Journals (Sweden)

    J. J. Middelburg

    2009-07-01

    Full Text Available The intensity, duration and frequency of coastal hypoxia (oxygen concentration <63 μM are increasing due to human alteration of coastal ecosystems and changes in oceanographic conditions due to global warming. Here we provide a concise review of the consequences of coastal hypoxia for sediment biogeochemistry. Changes in bottom-water oxygen levels have consequences for early diagenetic pathways (more anaerobic at expense of aerobic pathways, the efficiency of re-oxidation of reduced metabolites and the nature, direction and magnitude of sediment-water exchange fluxes. Hypoxia may also lead to more organic matter accumulation and burial and the organic matter eventually buried is also of higher quality, i.e. less degraded. Bottom-water oxygen levels also affect the organisms involved in organic matter processing with the contribution of metazoans decreasing as oxygen levels drop. Hypoxia has a significant effect on benthic animals with the consequences that ecosystem functions related to macrofauna such as bio-irrigation and bioturbation are significantly affected by hypoxia as well. Since many microbes and microbial-mediated biogeochemical processes depend on animal-induced transport processes (e.g. re-oxidation of particulate reduced sulphur and denitrification, there are indirect hypoxia effects on biogeochemistry via the benthos. Severe long-lasting hypoxia and anoxia may result in the accumulation of reduced compounds in sediments and elimination of macrobenthic communities with the consequences that biogeochemical properties during trajectories of decreasing and increasing oxygen may be different (hysteresis with consequences for coastal ecosystem dynamics.

  7. Initial results from the TST-2 spherical tokamak

    International Nuclear Information System (INIS)

    Takase, Y.; Ejiri, A.; Kasuya, N.

    2001-01-01

    A new spherical tokamak TST-2 was constructed at the University of Tokyo and started operation in September 1999. Reliable plasma initiation is achieved with typically 1 kW of ECH power at 2.45 GHz. Plasma currents of up to 90 kA and toroidal fields of up to 0.2 T have been achieved during the initial experimental campaign. The ion temperature is typically 100 eV. Internal reconnection events (IREs) are often observed. The internal magnetic field measured at r/a=2/3 indicated growth of fluctuations up to the 4 th harmonic, suggesting the existence of modes with several different mode numbers. In the presence of a toroidal field and a vertically oriented mirror field, noninductively driven currents of order 1 kA were observed with 1 kW of ECH power. The driven current increased with decreasing filling pressure, down to 3x10 -6 torr. A study of high harmonic fast wave (HHFW) excitation and propagation has begun. Initial results indicate highly efficient wave launching. (author)

  8. Experimental test accelerator: description and results of initial experiments

    International Nuclear Information System (INIS)

    Fessenden, T.; Birx, D.; Briggs, R.

    1980-01-01

    The ETA is a high current (10,000 Amp) linear induction accelerator that produces short (30 ns) pulses of electrons at 5 MeV twice per second or in bursts of 5 pulses separated by as little as one millisecond. At this time the machine has operated at 65% of its design current and 90% of the design voltage. This report contains a description of the accelerator and its diagnostics; the results of the initial year of operation; a comparison of design codes with experiments on beam transport; and a discussion of some of the special problems and their status

  9. Preliminary results from initial in-pile debris bed experiments

    International Nuclear Information System (INIS)

    Rivard, J.B.

    1977-01-01

    An accident in a liquid metal fast breeder reactor (LMFBR) in which molten core material is suddenly quenched with subcooled liquid sodium could result in extensive fragmentation and dispersal of fuel as subcritical beds of frozen particulate debris within the reactor vessel. Since this debris will continue to generate power due to decay of retained fission products, containment of the debris is threatened if the generated heat is not removed. Therefore, the initial safety question is the capacity which debris beds may have for transfer of the decay heat to overlying liquid sodium by natural processes--i.e., without the aid of forced circulation of the coolant. Up to the present time, all experiments on debris bed behavior either have used substitute materials (e.g., sand and water) or have employed actual materials, but atypical heating methods. Increased confidence in the applicability of debris bed simulations is afforded if the heat is generated within the fuel component of the appropriate fast reactor materials. The initial series of in-pile tests reported on herein constitutes the first experiments in which the internal heating mode has been produced in particulate oxide fuel immersed in liquid sodium. Fission heating of the fully-enriched UO 2 in the experiment while it is contained within Sandia Laboratories Annular Core Pulse Reactor (ACPR), operating in its steady-state mode, approximates the decay heating of debris. Preliminary results are discussed

  10. Initial CGE Model Results Summary Exogenous and Endogenous Variables Tests

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Brian Keith [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Boero, Riccardo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rivera, Michael Kelly [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-08-07

    The following discussion presents initial results of tests of the most recent version of the National Infrastructure Simulation and Analysis Center Dynamic Computable General Equilibrium (CGE) model developed by Los Alamos National Laboratory (LANL). The intent of this is to test and assess the model’s behavioral properties. The test evaluated whether the predicted impacts are reasonable from a qualitative perspective. This issue is whether the predicted change, be it an increase or decrease in other model variables, is consistent with prior economic intuition and expectations about the predicted change. One of the purposes of this effort is to determine whether model changes are needed in order to improve its behavior qualitatively and quantitatively.

  11. LWR aerosol containment experiments (LACE) program and initial test results

    International Nuclear Information System (INIS)

    Muhlestein, L.D.; Hilliard, R.K.; Bloom, G.R.; McCormack, J.D.; Rahn, F.J.

    1985-01-01

    The LWR aerosol containment experiments (LACE) program is described. The LACE program is being performed at the Hanford Engineer Development Laboratory (operated by Westinghouse Hanford Company) and the initial tests are sponsored by EPRI. The objectives of the LACE program are: to demonstrate, at large-scale, inherent radioactive aerosol retention behavior for postulated high consequence LWR accident situations; and to provide a data base to be used for aerosol behavior . Test results from the first phase of the LACE program are presented and discussed. Three large-scale scoping tests, simulating a containment bypass accident sequence, demonstrated the extent of agglomeration and deposition of aerosols occurring in the pipe pathway and vented auxiliary building under realistic accident conditions. Parameters varied during the scoping tests were aerosol type and steam condensation

  12. Mars Science Laboratory relative humidity observations: Initial results.

    Science.gov (United States)

    Harri, A-M; Genzer, M; Kemppinen, O; Gomez-Elvira, J; Haberle, R; Polkko, J; Savijärvi, H; Rennó, N; Rodriguez-Manfredi, J A; Schmidt, W; Richardson, M; Siili, T; Paton, M; Torre-Juarez, M De La; Mäkinen, T; Newman, C; Rafkin, S; Mischna, M; Merikallio, S; Haukka, H; Martin-Torres, J; Komu, M; Zorzano, M-P; Peinado, V; Vazquez, L; Urqui, R

    2014-09-01

    The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers. Atmospheric water mixing ratio at Gale crater varies from 30 to 140 ppmMSL relative humidity observation provides good dataHighest detected relative humidity reading during first MSL 100 sols is RH75.

  13. Midcervical neuronal discharge patterns during and following hypoxia

    Science.gov (United States)

    Sandhu, M. S.; Baekey, D. M.; Maling, N. G.; Sanchez, J. C.; Reier, P. J.

    2014-01-01

    Anatomical evidence indicates that midcervical interneurons can be synaptically coupled with phrenic motoneurons. Accordingly, we hypothesized that interneurons in the C3–C4 spinal cord can display discharge patterns temporally linked with inspiratory phrenic motor output. Anesthetized adult rats were studied before, during, and after a 4-min bout of moderate hypoxia. Neuronal discharge in C3–C4 lamina I–IX was monitored using a multielectrode array while phrenic nerve activity was extracellularly recorded. For the majority of cells, spike-triggered averaging (STA) of ipsilateral inspiratory phrenic nerve activity based on neuronal discharge provided no evidence of discharge synchrony. However, a distinct STA phrenic peak with a 6.83 ± 1.1 ms lag was present for 5% of neurons, a result that indicates a monosynaptic connection with phrenic motoneurons. The majority (93%) of neurons changed discharge rate during hypoxia, and the diverse responses included both increased and decreased firing. Hypoxia did not change the incidence of STA peaks in the phrenic nerve signal. Following hypoxia, 40% of neurons continued to discharge at rates above prehypoxia values (i.e., short-term potentiation, STP), and cells with initially low discharge rates were more likely to show STP (P phrenic motoneuron pool, and these cells can modulate inspiratory phrenic output. In addition, the C3–C4 propriospinal network shows a robust and complex pattern of activation both during and following an acute bout of hypoxia. PMID:25552641

  14. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Directory of Open Access Journals (Sweden)

    Seeley TW

    2017-03-01

    Full Text Available Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu Therapeutics R&D, FibroGen, Inc., San Francisco, CA, USA Abstract: The effects of pharmacological hypoxia-inducible factor (HIF stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF, using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs, FG-4497 or roxadustat (FG-4592. In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. Keywords: cancer progression, erythropoiesis, hypoxia-inducible factor, hypoxia-inducible factor prolyl hydroxylase inhibitors, vascular endothelial growth factor, MMTV-Neu breast cancer model

  15. Implementation of a quality improvement initiative in Belgian diabetic foot clinics: feasibility and initial results.

    Science.gov (United States)

    Doggen, Kris; Van Acker, Kristien; Beele, Hilde; Dumont, Isabelle; Félix, Patricia; Lauwers, Patrick; Lavens, Astrid; Matricali, Giovanni A; Randon, Caren; Weber, Eric; Van Casteren, Viviane; Nobels, Frank

    2014-07-01

    This article aims to describe the implementation and initial results of an audit-feedback quality improvement initiative in Belgian diabetic foot clinics. Using self-developed software and questionnaires, diabetic foot clinics collected data in 2005, 2008 and 2011, covering characteristics, history and ulcer severity, management and outcome of the first 52 patients presenting with a Wagner grade ≥ 2 diabetic foot ulcer or acute neuropathic osteoarthropathy that year. Quality improvement was encouraged by meetings and by anonymous benchmarking of diabetic foot clinics. The first audit-feedback cycle was a pilot study. Subsequent audits, with a modified methodology, had increasing rates of participation and data completeness. Over 85% of diabetic foot clinics participated and 3372 unique patients were sampled between 2005 and 2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both ischaemic and deeply infected. Ulcer healing rate at 6 months significantly increased from 49% to 54% between 2008 and 2011. Management of diabetic foot ulcers varied between diabetic foot clinics: 88% of plantar mid-foot ulcers were off-loaded (P10-P90: 64-100%), and 42% of ischaemic limbs were revascularized (P10-P90: 22-69%) in 2011. A unique, nationwide quality improvement initiative was established among diabetic foot clinics, covering ulcer healing, lower limb amputation and many other aspects of diabetic foot care. Data completeness increased, thanks in part to questionnaire revision. Benchmarking remains challenging, given the many possible indicators and limited sample size. The optimized questionnaire allows future quality of care monitoring in diabetic foot clinics. Copyright © 2014 John Wiley & Sons, Ltd.

  16. FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: Results from the DAHANCA 24 trial

    DEFF Research Database (Denmark)

    Mortensen, Lise Saksø; Johansen, Jørgen; Kallehauge, Jesper Folsted

    2012-01-01

    Hypoxia is a cause of resistance to radiotherapy, especially in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate (18)F-fluoroazomycin arabinoside (FAZA) positron emission tomography (PET)/computed tomography (CT) hypoxia imaging as a prognostic...

  17. Initial Results from Lunar Electromagnetic Sounding with ARTEMIS

    Science.gov (United States)

    Fuqua, H.; Fatemi, S.; Poppe, A. R.; Delory, G. T.; Grimm, R. E.; De Pater, I.

    2016-12-01

    Electromagnetic Sounding constrains conducting layers of the lunar interior by observing variations in the Interplanetary Magnetic Field. Here, we focus our analysis on the time domain transfer function method locating transient events observed by two magnetometers near the Moon. We analyze ARTEMIS and Apollo magnetometer data. This analysis assumes the induced field responds undisturbed in a vacuum. In actuality, the dynamic plasma environment interacts with the induced field. Our models indicate distortion but not confinement occurs in the nightside wake cavity. Moreover, within the deep wake, near-vacuum region, distortion of the induced dipole fields due to the interaction with the wake is minimal depending on the magnitude of the induced field, the geometry of the upstream fields, and the upstream plasma parameters such as particle densities, solar wind velocity, and temperatures. Our results indicate the assumption of a vacuum dipolar response is reasonable within this minimally disturbed zone. We then interpret the ATEMIS magnetic field signal through a geophysical forward model capturing the induced response based on prescribed electrical conductivity models. We demonstrate our forward model passes benchmarking analyses and solves the magnetic induction response for any input signal as well as any 2 or 3 dimensional conductivity profile. We locate data windows according to the following criteria: (1) probe locations such that the wake probe is within 500km altitude within the wake cavity and minimally disturbed zone, and the second probe is in the free streaming solar wind; (2) a transient event consisting of an abrupt change in the magnetic field occurs enabling the observation of induction; (3) cross correlation analysis reveals the magnetic field signals are well correlated between the two probes and distances observed. Here we present initial ARTEMIS results providing further insight into the lunar interior structure. This method and modeling results

  18. Initial water quantification results using neutron computed tomography

    Science.gov (United States)

    Heller, A. K.; Shi, L.; Brenizer, J. S.; Mench, M. M.

    2009-06-01

    Neutron computed tomography is an important imaging tool in the field of non-destructive testing and in fundamental research for many engineering applications. Contrary to X-rays, neutrons can be attenuated by some light materials, such as hydrogen, but can penetrate many heavy materials. Thus, neutron computed tomography is useful in obtaining important three-dimensional information about a sample's interior structure and material properties that other traditional methods cannot provide. The neutron computed tomography system at the Pennsylvania State University's Radiation Science and Engineering Center is being utilized to develop a water quantification technique for investigation of water distribution in fuel cells under normal conditions. A hollow aluminum cylinder test sample filled with a known volume of water was constructed for purposes of testing the quantification technique. Transmission images of the test sample at different angles were easily acquired through the synthesis of a dedicated image acquisition computer driving a rotary table controller and an in-house developed synchronization software package. After data acquisition, Octopus (version 8.2) and VGStudio Max (version 1.2) were used to perform cross-sectional and three-dimensional reconstructions of the sample, respectively. The initial reconstructions and water quantification results are presented.

  19. Initial results from the NSTX Real-Time Velocity diagnostic

    Science.gov (United States)

    Podesta, M.; Bell, R. E.

    2011-10-01

    A new diagnostic for fast measurements of plasma rotation through active charge-exchange recombination spectroscopy (CHERS) was installed on NSTX. The diagnostic infers toroidal rotation from carbon ions undergoing charge-exchange with neutrals from a heating Neutral Beam (NB). Each of the 4 channels, distributed along the outer major radius, includes active views intercepting the NB and background views missing the beam. Estimated uncertainties in the measured velocity are system. Signals are acquired on 2 CCD detectors, each controlled by a dedicated PC. Spectra are fitted in real-time through a C++ processing code and velocities are made available to the Plasma Control System for future implementation of feedback on velocity. Results from the initial operation during the 2011 run are discussed, emphasizing the fast dynamics of toroidal rotation, e . g . during L-H mode transition and breaking caused by instabilities and by externally-imposed magnetic perturbations. Work supported by USDOE Contract No. DE-AC02-09CH11466.

  20. Ground Operations Demonstration Unit for Liquid Hydrogen Initial Test Results

    Science.gov (United States)

    Notardonato, W. U.; Johnson, W. L.; Swanger, A. M.; Tomsik, T.

    2015-01-01

    NASA operations for handling cryogens in ground support equipment have not changed substantially in 50 years, despite major technology advances in the field of cryogenics. NASA loses approximately 50% of the hydrogen purchased because of a continuous heat leak into ground and flight vessels, transient chill down of warm cryogenic equipment, liquid bleeds, and vent losses. NASA Kennedy Space Center (KSC) needs to develop energy-efficient cryogenic ground systems to minimize propellant losses, simplify operations, and reduce cost associated with hydrogen usage. The GODU LH2 project has designed, assembled, and started testing of a prototype storage and distribution system for liquid hydrogen that represents an advanced end-to-end cryogenic propellant system for a ground launch complex. The project has multiple objectives including zero loss storage and transfer, liquefaction of gaseous hydrogen, and densification of liquid hydrogen. The system is unique because it uses an integrated refrigeration and storage system (IRAS) to control the state of the fluid. This paper will present and discuss the results of the initial phase of testing of the GODU LH2 system.

  1. Initial water quantification results using neutron computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Heller, A.K. [Department of Mechanical and Nuclear Engineering, Pennsylvania State University (United States)], E-mail: axh174@psu.edu; Shi, L.; Brenizer, J.S.; Mench, M.M. [Department of Mechanical and Nuclear Engineering, Pennsylvania State University (United States)

    2009-06-21

    Neutron computed tomography is an important imaging tool in the field of non-destructive testing and in fundamental research for many engineering applications. Contrary to X-rays, neutrons can be attenuated by some light materials, such as hydrogen, but can penetrate many heavy materials. Thus, neutron computed tomography is useful in obtaining important three-dimensional information about a sample's interior structure and material properties that other traditional methods cannot provide. The neutron computed tomography system at Pennsylvania State University's Radiation Science and Engineering Center is being utilized to develop a water quantification technique for investigation of water distribution in fuel cells under normal conditions. A hollow aluminum cylinder test sample filled with a known volume of water was constructed for purposes of testing the quantification technique. Transmission images of the test sample at different angles were easily acquired through the synthesis of a dedicated image acquisition computer driving a rotary table controller and an in-house developed synchronization software package. After data acquisition, Octopus (version 8.2) and VGStudio Max (version 1.2) were used to perform cross-sectional and three-dimensional reconstructions of the sample, respectively. The initial reconstructions and water quantification results are presented.

  2. Application of Terahertz Radiation to Soil Measurements: Initial Results

    Science.gov (United States)

    Dworak, Volker; Augustin, Sven; Gebbers, Robin

    2011-01-01

    Developing soil sensors with the possibility of continuous online measurement is a major challenge in soil science. Terahertz (THz) electromagnetic radiation may provide the opportunity for the measurement of organic material density, water content and other soil parameters at different soil depths. Penetration depth and information content is important for a functional soil sensor. Therefore, we present initial research on the analysis of absorption coefficients of four different soil samples by means of THz transmission measurements. An optimized soil sample holder to determine absorption coefficients was used. This setup improves data acquisition because interface reflections can be neglected. Frequencies of 340 GHz to 360 GHz and 1.627 THz to 2.523 THz provided information about an existing frequency dependency. The results demonstrate the potential of this THz approach for both soil analysis and imaging of buried objects. Therefore, the THz approach allows different soil samples to be distinguished according to their different absorption properties so that relations among soil parameters may be established in future. PMID:22163737

  3. NICER observations of highly magnetized neutron stars: Initial results

    Science.gov (United States)

    Enoto, Teruaki; Arzoumanian, Zaven; Gendreau, Keith C.; Nynka, Melania; Kaspi, Victoria; Harding, Alice; Guver, Tolga; Lewandowska, Natalia; Majid, Walid; Ho, Wynn C. G.; NICER Team

    2018-01-01

    The Neutron star Interior Composition Explorer (NICER) was launched on June 3, 2017, and attached to the International Space Station. The large effective area of NICER in soft X-rays makes it a powerful tool not only for its primary science objective (diagnostics of the nuclear equation state) but also for studying neutron stars of various classes. As one of the NICER science working groups, the Magnetars and Magnetospheres (M&M) team coordinates monitoring and target of opportunity (ToO) observations of magnetized neutron stars, including magnetars, high-B pulsars, X-ray dim isolated neutron stars, and young rotation-powered pulsars. The M&M working group has performed simultaneous X-ray and radio observations of the Crab and Vela pulsars, ToO observations of the active anomalous X-ray pulsar 4U 0142+61, and a monitoring campaign for the transient magnetar SGR 0501+4516. Here we summarize the current status and initial results of the M&M group.

  4. Initial Results from the New Stress Map of Texas Project

    Science.gov (United States)

    Lund Snee, J. E.; Zoback, M. D.

    2015-12-01

    Modern techniques for characterizing tectonic stress orientation and relative magnitude have been successfully used for more than 35 years. Nevertheless, large areas of North America lack high spatial resolution maps of stress orientation, magnitude, and faulting regime. In Texas, for example, data are foundational elements of attempts to characterize tectonic driving forces, understand hazards associated with induced seismicity, and optimize production of oil, gas, and geothermal resources. This year, we launched the Texas Stress Map project to characterize tectonic stress patterns at higher spatial resolution across Texas and nearby areas. Following a successful effort just completed in Oklahoma, we will evaluate borehole breakouts, drilling-induced tensile fractures, shear wave anisotropy, and earthquake data. The principal data source will be FMI (fullbore formation microimager), UBI (ultrasonic borehole imager), cross-dipole sonic, density, and caliper logs provided by private industry. Earthquake moment tensor solutions from the U.S. Geological Survey, Saint Louis University and other sources will also be used. Our initial focus is on the Permian Basin and Barnett Shale petroleum plays due to the availability of data, but we will expand our analysis across the state as the project progresses. In addition, we hope to eventually apply the higher spatial resolution data coverage to understanding tectonic and geodynamic characteristics of the southwestern United States and northeastern Mexico. Here we present early results from our work to constrain stress orientations and faulting regime in and near Texas, and we also provide a roadmap for the ongoing research.

  5. Initial results from the fast imaging solar spectrograph (FISS)

    CERN Document Server

    2015-01-01

    This collection of papers describes the instrument and initial results obtained from the Fast Imaging Solar Spectrograph (FISS),  one of the post-focus instruments of the 1.6 meter New Solar Telescope at the Big Bear Solar Observatory. The FISS primarily aims at investigating structures and dynamics of  chromospheric features. This instrument is a dual-band Echelle spectrograph optimized for the simultaneous recording of the H I 656.3 nm band and the Ca II 854.2 nm band. The imaging is done with the fast raster scan realized by the linear motion of a two-mirror scanner, and its quality is determined by the performance of the adaptive optics of the telescope.    These papers illustrate the capability of the early FISS observations in the study of chromospheric features. Since the imaging quality has been improved a lot with the advance of the adaptive optics, one can obtain much better data with the current FISS observations.        This volume is aimed at graduate students and researchers working in...

  6. Site Specific Advisory Board initiative, evaluation survey results supplementary appendix: Summary of individual site results

    International Nuclear Information System (INIS)

    1996-08-01

    This Appendix presents results of the Site-Specific Advisory Board (SSAB) Initiative for each of the 11 sites that participated in the survey. These individual results are a supplement to the June 1996 Summary Report which presented overall survey results. Results are presented in 11 sections, arranged alphabetically by site. Each section includes a series of figures and tables that parallel those presented in the Summary Report. To facilitate comparison, figures are presented both for the individual site and for the overall long survey. The sequence of sections is: Fernald, Hanford, Idaho, Los Alamos, Monticello, Nevada, Pantex, Rocky Flats, St. Louis, Sandia, and Savannah River

  7. The Frontier Fields: Survey Design and Initial Results

    Energy Technology Data Exchange (ETDEWEB)

    Lotz, J. M.; Koekemoer, A.; Grogin, N.; Mack, J.; Anderson, J.; Avila, R.; Barker, E. A.; Borncamp, D.; Durbin, M.; Gunning, H.; Hilbert, B.; Jenkner, H.; Khandrika, H.; Levay, Z.; Lucas, R. A.; MacKenty, J.; Ogaz, S. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Coe, D.; Capak, P.; Brammer, G., E-mail: lotz@stsci.edu [European Space Agency/Space Telescope Science Institute, 3700 Sam Martin Drive, Baltimore, MD 21218 (United States); and others

    2017-03-01

    What are the faintest distant galaxies we can see with the Hubble Space Telescope ( HST ) now, before the launch of the James Webb Space Telescope ? This is the challenge taken up by the Frontier Fields, a Director’s discretionary time campaign with HST and the Spitzer Space Telescope to see deeper into the universe than ever before. The Frontier Fields combines the power of HST and Spitzer with the natural gravitational telescopes of massive high-magnification clusters of galaxies to produce the deepest observations of clusters and their lensed galaxies ever obtained. Six clusters—Abell 2744, MACSJ0416.1-2403, MACSJ0717.5+3745, MACSJ1149.5+2223, Abell S1063, and Abell 370—have been targeted by the HST ACS/WFC and WFC3/IR cameras with coordinated parallel fields for over 840 HST orbits. The parallel fields are the second-deepest observations thus far by HST with 5 σ point-source depths of ∼29th ABmag. Galaxies behind the clusters experience typical magnification factors of a few, with small regions magnified by factors of 10–100. Therefore, the Frontier Field cluster HST images achieve intrinsic depths of ∼30–33 mag over very small volumes. Spitzer has obtained over 1000 hr of Director’s discretionary imaging of the Frontier Field cluster and parallels in IRAC 3.6 and 4.5 μ m bands to 5 σ point-source depths of ∼26.5, 26.0 ABmag. We demonstrate the exceptional sensitivity of the HST Frontier Field images to faint high-redshift galaxies, and review the initial results related to the primary science goals.

  8. DART Core/Combustor-Noise Initial Test Results

    Science.gov (United States)

    Boyle, Devin K.; Henderson, Brenda S.; Hultgren, Lennart S.

    2017-01-01

    Contributions from the combustor to the overall propulsion noise of civilian transport aircraft are starting to become important due to turbofan design trends and advances in mitigation of other noise sources. Future propulsion systems for ultra-efficient commercial air vehicles are projected to be of increasingly higher bypass ratio from larger fans combined with much smaller cores, with ultra-clean burning fuel-flexible combustors. Unless effective noise-reduction strategies are developed, combustor noise is likely to become a prominent contributor to overall airport community noise in the future. The new NASA DGEN Aero0propulsion Research Turbofan (DART) is a cost-efficient testbed for the study of core-noise physics and mitigation. This presentation gives a brief description of the recently completed DART core combustor-noise baseline test in the NASA GRC Aero-Acoustic Propulsion Laboratory (AAPL). Acoustic data was simultaneously acquired using the AAPL overhead microphone array in the engine aft quadrant far field, a single midfield microphone, and two semi-infinite-tube unsteady pressure sensors at the core-nozzle exit. An initial assessment shows that the data is of high quality and compares well with results from a quick 2014 feasibility test. Combustor noise components of measured total-noise signatures were educed using a two-signal source-separation method an dare found to occur in the expected frequency range. The research described herein is aligned with the NASA Ultra-Efficient Commercial Transport strategic thrust and is supported by the NASA Advanced Air Vehicle Program, Advanced Air Transport Technology Project, under the Aircraft Noise Reduction Subproject.

  9. FFTF initial fuel loading, preanalyses, and comparison with preliminary results

    International Nuclear Information System (INIS)

    Rothrock, R.B.; Daughtry, J.W.; Zimmerman, B.D.; Petrowicz, N.E.; Bennett, R.A.; Ombrellaro, P.A.

    1980-02-01

    Disadvantages of conventional loading from the center out were circumvented by loading one trisector at a time, and connecting the control rod drivelines in each sector after it was loaded so that the rods could be operated during the loading of subsequent trisectors. This sequence was interrupted once during the loading of the final sector, to achieve initial criticality at an approximately minimum critical loading and to measure absolute subcriticality by the rod drop technique. An in-core detector was preferable to the standard FTR ex-core detectors for monitoring the initial fuel loading. Consequently, special fission chambers were installed in an instrument thimble near the core center to monitor the initial fuel loading

  10. Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

    Directory of Open Access Journals (Sweden)

    Christoph M Zehendner

    Full Text Available Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR on the evolution of reactive oxygen species (ROS and blood-brain barrier (BBB integrity in brain endothelial cells (BEC. BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC or towards occlusion of the arteria cerebri media (MCAO with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF, MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1 and claudin 5 (Cl5, decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role

  11. Initial Results from Coaxial Helicity Injection Experiments in NSTX

    International Nuclear Information System (INIS)

    Raman, R.; Jarboe, T.R.; Mueller, D.; Schaffer, M.J.; Maqueda, R.; Nelson, B.A.; Sabbagh, S.; Bell, M.; Ewig, R.; Fredrickson, E.; Gates, D.; Hosea, J.; Ji, H.; Kaita, R.; Kaye, S.M.; Kugel, H.; Maingi, R.; Menard, J.; Ono, M.; Orvis, D.; Paolette, F.; Paul, S.; Peng, M.; Skinner, C.H.; Wilgen, W.; Zweben, S.

    2001-01-01

    Coaxial Helicity Injection (CHI) has been investigated on the National Spherical Torus Experiment (NSTX). Initial experiments produced 130 kA of toroidal current without the use of the central solenoid. The corresponding injector current was 20 kA. Discharges with pulse lengths up to 130 ms have been produced

  12. Initial results in SST-1 after up-gradation

    Science.gov (United States)

    Pradhan, S.; Khan, Z.; Tanna, V. L.; Prasad, U.; Paravastu, Y.; Raval, D. C.; Masand, H.; Kumar, Aveg; Dhongde, J. R.; Jana, S.; Kakati, B.; Patel, K. B.; Bhandarkar, M. K.; Shukla, B. K.; Ghosh, D.; Patel, H. S.; Parekh, T. J.; Mansuri, I. A.; Dhanani, K. R.; Varadharajulu, A.; Khristi, Y. S.; Biswas, P.; Gupta, C. N.; George, S.; Semwal, P.; Sharma, D. K.; Gulati, H. K.; Mahajan, K.; Praghi, B. R.; Banaudha, M.; Makwana, A. R.; Chudasma, H. H.; Kumar, M.; Manchanda, R.; Joisa, Y. S.; Asudani, K.; Pandya, S. N.; Pathak, S. K.; Banerjee, S.; Patel, P. J.; Santra, P.; Pathan, F. S.; Chauhan, P. K.; Khan, M. S.; Thankey, P. L.; Prakash, A.; Panchal, P. N.; Panchal, R. N.; Patel, R. J.; Mahsuria, G. I.; Sonara, D. P.; Patel, K. M.; Jayaswal, S. P.; Sharma, M.; Patel, J. C.; Varmora, P.; Srikanth, G. L. N.; Christian, D. R.; Garg, A.; Bairagi, N.; Babu, G. R.; Panchal, A. G.; Vora, M. M.; Singh, A. K.; Sharma, R.; Nimavat, H. D.; Shah, P. R.; Purwar, G.; Raval, T. Y.; Sharma, A. L.; Ojha, A.; Kumar, S.; Ramaiya, N. K.; Siju, V.; Gopalakrishna, M. V.; Kumar, A.; Sharma, P. K.; Atrey, P. K.; Kulkarni, SV; Ambulkar, K. K.; Parmar, P. R.; Thakur, A. L.; Raval, J. V.; Purohit, S.; Mishra, P. K.; Adhiya, A. N.; Nagora, U. C.; Thomas, J.; Chaudhari, V. K.; Patel, K. G.; Dalakoti, S.; Virani, C. G.; Gupta, S.; Kumar, Ajay; Chaudhari, B.; Kaur, R.; Srinivasan, R.; Raju, D.; Kanabar, D. H.; Jha, R.; Das, A.; Bora, D.

    2017-04-01

    SST-1 Tokamak has recently completed the 1st phase of up-gradation with successful installation and integration of all its First Wall components. The First Wall of SST-1 comprises of ∼ 3800 high heat flux compatible graphite tiles being assembled and installed on 132 CuCrZr heat sink back plates engraved with ∼ 4 km of leak tight baking and cooling channels in five major sub groups equipped with ∼ 400 sensors and weighing ∼ 6000 kg in total in thirteen isolated galvanic and six isolated hydraulic circuits. The phase-1 up-gradation spectrum also includes addition of Supersonic Molecular Beam Injection (SMBI) both on the in-board and out-board side, installation of fast reciprocating probes, adding some edge plasma probe diagnostics in the SOL region, installation and integration of segmented and up-down symmetric radial coils aiding/controlling plasma rotations, introduction of plasma position feedback and density controls etc. Post phase-I up-gradation spanning from Nov 2014 till June 2016, initial plasma experiments in up-graded SST-1 have begun since Aug 2016 after a brief engineering validation period in SST-1. The first experiments in SST-1 have revealed interesting aspects on the ‘eddy currents in the First Wall support structures’ influencing the ‘magnetic Null evolution dynamics’ and the subsequent plasma start-up characteristics after the ECH pre-ionization, the influence of the first walls on the ‘field errors’ and the resulting locked modes observed, the magnetic index influencing the evolution of the equilibrium of the plasma column, low density supra-thermal electron induced discharges and normal ohmic discharges etc. Presently; repeatable ohmic discharges regimes in SST-1 having plasma currents in excess of 65 KA (qa ∼ 3.8, BT = 1.5 T) with a current ramp rates ∼ 1.2 MA/s over a duration of ∼ 300 ms with line averaged densities ∼ 0.8 × 1019 and temperatures ∼ 200 eV with copious MHD signatures have been experimentally

  13. Hypoxia triggers short term potentiation of phrenic motoneuron discharge after chronic cervical spinal cord injury

    Science.gov (United States)

    Lee, Kun-Ze; Sandhu, Milapjit S.; Dougherty, Brendan J.; Reier, Paul J.; Fuller, David D.

    2014-01-01

    Repeated exposure to hypoxia can induce spinal neuroplasticity as well as respiratory and somatic motor recovery after spinal cord injury (SCI). The purpose of the present study was to define the capacity for a single bout of hypoxia to trigger short-term plasticity in phrenic output after cervical SCI, and to determine the phrenic motoneuron (PhrMN) bursting and recruitment patterns underlying the response. Hypoxia-induced short term potentiation (STP) of phrenic motor output was quantified in anesthetized rats 11 wks following lateral spinal hemisection at C2 (C2Hx). A 3-min hypoxic episode (12–14% O2) always triggered STP of inspiratory burst amplitude, the magnitude of which was greater in phrenic bursting ipsilateral vs. contralateral to C2Hx. We next determined if STP could be evoked in recruited (silent) PhrMNs ipsilateral to C2Hx. Individual PhrMN action potentials were recorded during and following hypoxia using a “single fiber” approach. STP of bursting activity did not occur in cells initiating bursting at inspiratory onset, but was robust in recruited PhrMNs as well as previously active cells initiating bursting later in the inspiratory effort. We conclude that following chronic C2Hx, a single bout of hypoxia triggers recruitment of PhrMNs in the ipsilateral spinal cord with bursting that persists beyond the hypoxic exposure. The results provide further support for the use of short bouts of hypoxia as a neurorehabilitative training modality following SCI. PMID:25448009

  14. Hypoxia training: symptom replication in experienced military aircrew.

    Science.gov (United States)

    Johnston, Ben J; Iremonger, Gareth S; Hunt, Sheena; Beattie, Elizabeth

    2012-10-01

    Military aircrew are trained to recognize the signs and symptoms of hypoxia in a safe environment using a variety of methods to simulate altitude. In order to investigate the effectiveness of hypoxia training, this study compared the recall of hypoxia symptoms in military aircrew between two consecutive hypobaric chamber hypoxia training sessions conducted, on average, 4.5 yr apart. Previously trained subjects completed a questionnaire immediately before and after they underwent refresher hypoxia training and recorded the occurrence, order, and severity of symptoms experienced. Responses from refresher training were compared with their recall of symptoms experienced during previous training. There was no difference in the recall of most hypoxia symptoms between training sessions. Slurred speech was recalled more frequently from previous training compared to refresher training (14 vs. 4 subjects), whereas hot/cold flushes were recalled less frequently from previous training compared to refresher training (5 vs. 17 subjects). There was a statistically significant difference in overall hypoxia score (10.3 vs. 8.3), suggesting that from memory subjects may underestimate the level of hypoxia experienced in previous training. A high level of similarity between the recall of previously experienced hypoxia symptoms and recent experience supports the effectiveness of hypoxia training. These results replicate the finding of a 'hypoxia signature' reported by a previous study. Small differences in the recall of some symptoms and in overall hypoxia score highlight the importance of drawing attention to the more subtle symptoms of early hypoxia, and of using training techniques which optimize aircrew recall.

  15. Ecosystem impacts of hypoxia: thresholds of hypoxia and pathways to recovery

    International Nuclear Information System (INIS)

    Steckbauer, A; Duarte, C M; Vaquer-Sunyer, R; Carstensen, J; Conley, D J

    2011-01-01

    Coastal hypoxia is increasing in the global coastal zone, where it is recognized as a major threat to biota. Managerial efforts to prevent hypoxia and achieve recovery of ecosystems already affected by hypoxia are largely based on nutrient reduction plans. However, these managerial efforts need to be informed by predictions on the thresholds of hypoxia (i.e. the oxygen levels required to conserve biodiversity) as well as the timescales for the recovery of ecosystems already affected by hypoxia. The thresholds for hypoxia in coastal ecosystems are higher than previously thought and are not static, but regulated by local and global processes, being particularly sensitive to warming. The examination of recovery processes in a number of coastal areas managed for reducing nutrient inputs and, thus, hypoxia (Northern Adriatic; Black Sea; Baltic Sea; Delaware Bay; and Danish Coastal Areas) reveals that recovery timescales following the return to normal oxygen conditions are much longer than those of loss following the onset of hypoxia, and typically involve decadal timescales. The extended lag time for ecosystem recovery from hypoxia results in non-linear pathways of recovery due to hysteresis and the shift in baselines, affecting the oxygen thresholds for hypoxia through time.

  16. A first glance at the initial ATF experimental results

    International Nuclear Information System (INIS)

    Carreras, B.A.; Dominguez, N.; Leboeuf, J.N.; Lynch, V.E.; Charlton, L.A.

    1989-05-01

    In the initial phase of ATF operation, the plasma minor radius and the edge rotational transform were reduced by field errors. This caused an effective change of the magnetic configuration: it improved the stability properties but worsened the equilibrium properties. The threshold for the second stability regime was lowered to β 0 /approximately/ 1.5%. Experimental profile data are compatible with operation in the second stability regime, and the achieved beta values, β 0 /approximately/ 3%, are well beyond the theoretically calculated threshold. Magnetic fluctuation measurements showed the effects of beta self-stabilization. They are in reasonable agreement with the predictions of the theory and support the evidence that ATF has already operated in the second stability regime. 24 refs., 20 figs., 1 tab

  17. Initial results of a positron tomograph for prostate imaging

    Energy Technology Data Exchange (ETDEWEB)

    Huber, J.S.; Choong, W.S.; Moses, W.W.; Qi, J.; Hu, J.; Wang,G.C.; Wilson, D.; Oh, S.; Huesman, R.H.; Derenzo, S.E.; Budinger, T.F.

    2004-11-29

    We present the status and initial images of a positrontomograph for prostate imaging that centers a patient between a pair ofexternal curved detector banks (ellipse: 45 cm minor, 70 cm major axis).The distance between detector banks adjusts to allow patient access andto position the detectors as closely as possible for maximum sensitivitywith patients of various sizes. Each bank is composed of two axial rowsof 20 CTI PET Systems HR+ block detectors for a total of 80 modules inthe camera. Compared to an ECAT HR PET system operating in 3D mode, ourcamera uses about one-quarter the number of detectors and hasapproximately the same sensitivity for a central point source, becauseour detectors are close to the patient. The individual detectors areangled in the plane to point towards the prostate to minimize resolutiondegradation in that region. The detectors are read out by modified CTIdata acquisition electronics. We have completed construction of thegantry and electronics, have developed detector calibration and dataacquisition software, and are taking coincidence data. We demonstratethat we can clearly visualize a "prostate" in a simple phantom.Reconstructed images of two phantoms are shown.

  18. Initial results of Pakistan's first road traffic injury surveillance project.

    Science.gov (United States)

    Shamim, Shahzad; Razzak, Junaid A; Jooma, Rashid; Khan, Uzma

    2011-09-01

    Our aim is to report the findings of the initial three years of road traffic injuries (RTI) surveillance at Karachi and to compare it with previously published RTI-related data from Pakistan and other low-and middle-income countries. Data were collected through the RTI surveillance programme at Karachi (RTIRP) from the five biggest emergency departments of the city, which receive almost all the major emergencies of the city for the period September 2006 till September 2009. A total of 99,272 victims were enlisted by the RTIRP during the study period. Annual incidence of RTI is calculated to be 184.3 per 100,000 populations and mortality is 5.7 per 100,000 populations. Eighty nine per cent of victims are male and 73% are between 15 and 44 years of age. Commonest road user to be affected is riders of two wheelers (45%). Only 7% of affected motorcyclists were found to be wearing helmets at the time of the accident. Trends of injuries remained uniform over the years. Most frequent injuries were external wounds, followed by orthopaedic injuries. On the basis of our surveillance system, we have presented the largest RTI-related data from a metropolitan city of Pakistan to date.

  19. Quantitative MR imaging in fracture dating--Initial results.

    Science.gov (United States)

    Baron, Katharina; Neumayer, Bernhard; Widek, Thomas; Schick, Fritz; Scheicher, Sylvia; Hassler, Eva; Scheurer, Eva

    2016-04-01

    For exact age determinations of bone fractures in a forensic context (e.g. in cases of child abuse) improved knowledge of the time course of the healing process and use of non-invasive modern imaging technology is of high importance. To date, fracture dating is based on radiographic methods by determining the callus status and thereby relying on an expert's experience. As a novel approach, this study aims to investigate the applicability of magnetic resonance imaging (MRI) for bone fracture dating by systematically investigating time-resolved changes in quantitative MR characteristics after a fracture event. Prior to investigating fracture healing in children, adults were examined for this study in order to test the methodology for this application. Altogether, 31 MR examinations in 17 subjects (♀: 11 ♂: 6; median age 34 ± 15 y, scanned 1-5 times over a period of up to 200 days after the fracture event) were performed on a clinical 3T MR scanner (TimTrio, Siemens AG, Germany). All subjects were treated conservatively for a fracture in either a long bone or in the collar bone. Both, qualitative and quantitative MR measurements were performed in all subjects. MR sequences for a quantitative measurement of relaxation times T1 and T2 in the fracture gap and musculature were applied. Maps of quantitative MR parameters T1, T2, and magnetisation transfer ratio (MTR) were calculated and evaluated by investigating changes over time in the fractured area by defined ROIs. Additionally, muscle areas were examined as reference regions to validate this approach. Quantitative evaluation of 23 MR data sets (12 test subjects, ♀: 7 ♂: 5) showed an initial peak in T1 values in the fractured area (T1=1895 ± 607 ms), which decreased over time to a value of 1094 ± 182 ms (200 days after the fracture event). T2 values also peaked for early-stage fractures (T2=115 ± 80 ms) and decreased to 73 ± 33 ms within 21 days after the fracture event. After that time point, no

  20. Complex decision-making: initial results of an empirical study

    Directory of Open Access Journals (Sweden)

    Pier Luigi Baldi

    2011-09-01

    Full Text Available A brief survey of key literature on emotions and decision-making introduces an empirical study of a group of university students exploring the effects of decision-making complexity on error risk. The results clearly show that decision-making under stress in the experimental group produces significantly more errors than in the stress-free control group.

  1. Complex decision-making: initial results of an empirical study

    OpenAIRE

    Pier Luigi Baldi

    2011-01-01

    A brief survey of key literature on emotions and decision-making introduces an empirical study of a group of university students exploring the effects of decision-making complexity on error risk. The results clearly show that decision-making under stress in the experimental group produces significantly more errors than in the stress-free control group.

  2. Alternative multi-user interaction screen: initial ergonomic test results

    CSIR Research Space (South Africa)

    Smith, Andrew C

    2010-05-01

    Full Text Available excitement. In some instances the recording volume was too low and the recording had to be repeated. Participants were very keen to record their own sound clip and the activity would invariably result in general laughter when played back. We captured...

  3. Initial Results of a New Mobile Spectrum Occupancy Monitoring Network

    NARCIS (Netherlands)

    van Bloem, J.W.H.; Schiphorst, Roelof; Slump, Cornelis H.

    2010-01-01

    In this paper we present results of the new monitoring network for spectrum governance. The network is based on the RFeye system of CRFS where the data is collected employing mobile monitoring vehicles. The measurement data, obtained from a frequency sweep between 10 MHz and 6 GHz, is further

  4. Small-Scale Spray Releases: Initial Aerosol Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Mahoney, Lenna A.; Gauglitz, Phillip A.; Kimura, Marcia L.; Brown, Garrett N.; Kurath, Dean E.; Buchmiller, William C.; Smith, Dennese M.; Blanchard, Jeremy; Song, Chen; Daniel, Richard C.; Wells, Beric E.; Tran, Diana N.; Burns, Carolyn A.

    2013-05-29

    One of the events postulated in the hazard analysis at the Waste Treatment and Immobilization Plant (WTP) and other U.S. Department of Energy (DOE) nuclear facilities is a breach in process piping that produces aerosols with droplet sizes in the respirable range. The current approach for predicting the size and concentration of aerosols produced in a spray leak involves extrapolating from correlations reported in the literature. These correlations are based on results obtained from small engineered spray nozzles using pure liquids with Newtonian fluid behavior. The narrow ranges of physical properties on which the correlations are based do not cover the wide range of slurries and viscous materials that will be processed in the WTP and across processing facilities in the DOE complex. Two key technical areas were identified where testing results were needed to improve the technical basis by reducing the uncertainty due to extrapolating existing literature results. The first technical need was to quantify the role of slurry particles in small breaches where the slurry particles may plug and result in substantially reduced, or even negligible, respirable fraction formed by high-pressure sprays. The second technical need was to determine the aerosol droplet size distribution and volume from prototypic breaches and fluids, specifically including sprays from larger breaches with slurries where data from the literature are scarce. To address these technical areas, small- and large-scale test stands were constructed and operated with simulants to determine aerosol release fractions and net generation rates from a range of breach sizes and geometries. The properties of the simulants represented the range of properties expected in the WTP process streams and included water, sodium salt solutions, slurries containing boehmite or gibbsite, and a hazardous chemical simulant. The effect of antifoam agents was assessed with most of the simulants. Orifices included round holes and

  5. Small-Scale Spray Releases: Initial Aerosol Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Mahoney, Lenna A.; Gauglitz, Phillip A.; Kimura, Marcia L.; Brown, Garrett N.; Kurath, Dean E.; Buchmiller, William C.; Smith, Dennese M.; Blanchard, Jeremy; Song, Chen; Daniel, Richard C.; Wells, Beric E.; Tran, Diana N.; Burns, Carolyn A.

    2012-11-01

    One of the events postulated in the hazard analysis at the Waste Treatment and Immobilization Plant (WTP) and other U.S. Department of Energy (DOE) nuclear facilities is a breach in process piping that produces aerosols with droplet sizes in the respirable range. The current approach for predicting the size and concentration of aerosols produced in a spray leak involves extrapolating from correlations reported in the literature. These correlations are based on results obtained from small engineered spray nozzles using pure liquids with Newtonian fluid behavior. The narrow ranges of physical properties on which the correlations are based do not cover the wide range of slurries and viscous materials that will be processed in the WTP and across processing facilities in the DOE complex. Two key technical areas were identified where testing results were needed to improve the technical basis by reducing the uncertainty due to extrapolating existing literature results. The first technical need was to quantify the role of slurry particles in small breaches where the slurry particles may plug and result in substantially reduced, or even negligible, respirable fraction formed by high-pressure sprays. The second technical need was to determine the aerosol droplet size distribution and volume from prototypic breaches and fluids, specifically including sprays from larger breaches with slurries where data from the literature are scarce. To address these technical areas, small- and large-scale test stands were constructed and operated with simulants to determine aerosol release fractions and generation rates from a range of breach sizes and geometries. The properties of the simulants represented the range of properties expected in the WTP process streams and included water, sodium salt solutions, slurries containing boehmite or gibbsite, and a hazardous chemical simulant. The effect of anti-foam agents was assessed with most of the simulants. Orifices included round holes and

  6. Large-Scale Spray Releases: Initial Aerosol Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Schonewill, Philip P.; Gauglitz, Phillip A.; Bontha, Jagannadha R.; Daniel, Richard C.; Kurath, Dean E.; Adkins, Harold E.; Billing, Justin M.; Burns, Carolyn A.; Davis, James M.; Enderlin, Carl W.; Fischer, Christopher M.; Jenks, Jeromy WJ; Lukins, Craig D.; MacFarlan, Paul J.; Shutthanandan, Janani I.; Smith, Dennese M.

    2012-12-01

    One of the events postulated in the hazard analysis at the Waste Treatment and Immobilization Plant (WTP) and other U.S. Department of Energy (DOE) nuclear facilities is a breach in process piping that produces aerosols with droplet sizes in the respirable range. The current approach for predicting the size and concentration of aerosols produced in a spray leak involves extrapolating from correlations reported in the literature. These correlations are based on results obtained from small engineered spray nozzles using pure liquids with Newtonian fluid behavior. The narrow ranges of physical properties on which the correlations are based do not cover the wide range of slurries and viscous materials that will be processed in the WTP and across processing facilities in the DOE complex. Two key technical areas were identified where testing results were needed to improve the technical basis by reducing the uncertainty due to extrapolating existing literature results. The first technical need was to quantify the role of slurry particles in small breaches where the slurry particles may plug and result in substantially reduced, or even negligible, respirable fraction formed by high-pressure sprays. The second technical need was to determine the aerosol droplet size distribution and volume from prototypic breaches and fluids, specifically including sprays from larger breaches with slurries where data from the literature are scarce. To address these technical areas, small- and large-scale test stands were constructed and operated with simulants to determine aerosol release fractions and generation rates from a range of breach sizes and geometries. The properties of the simulants represented the range of properties expected in the WTP process streams and included water, sodium salt solutions, slurries containing boehmite or gibbsite, and a hazardous chemical simulant. The effect of anti-foam agents was assessed with most of the simulants. Orifices included round holes and

  7. Initial results from the Donner 600-crystal positron tomograph

    International Nuclear Information System (INIS)

    Derenzo, S.E.; Huesman, R.H.; Cahoon, J.L.; Geyer, A.B.; Uber, D.C.; Vuletich, T.; Budinger, T.F.

    1987-01-01

    These results show the 3-mm BGO crystals can improve the resolution in positron tomography by a substantial factor. This measured crystal-pair resolution of 2.4 mm FWHM and the reconstructed image resolution of 2.9 mm FWHM at the center of the tomograph are in good agreement with expected values. The most serious limitation of the detector design is that only a single section can be imaged. 4 refs., 4 figs

  8. Results of initial nuclear tests on LWBR (LWBR Development Program)

    International Nuclear Information System (INIS)

    Sarber, W.K.

    1979-06-01

    This report presents and discusses the results of physics tests performed at beginning of life on the Light Water Breeder Reactor (LWBR). These tests have confirmed that movable seed assembly critical positions and reactivity worths, temperature coefficients, xenon transient characteristics, core symmetry, and core shutdown are within the range of values used in the design of the LWBR and its reactor protection analysis. Measured core physics parameters were found to be in good agreement with the calculated values

  9. Initial commissioning results from the APS loss monitor system

    International Nuclear Information System (INIS)

    Patterson, D.R.

    1996-01-01

    The design of the beam loss monitor system for the Argonne National Laboratory Advanced Photon Source is based on using a number of air dielectric coaxial cables as long ionization chambers. Results to date show that the loss monitor is useful in helping to determine the cause of injection losses and losses large enough to limit circulating currents in the storage ring to short lifetimes. Sensitivities ranging from 13 to 240 pC of charge collected in the injector BTS (booster-to-storage-ring) loss monitor per picocoulomb of loss have been measured, depending on the loss location. These results have been used to predict that the storage ring loss monitor leakage current limit of 10 pA per cable should allow detection of losses resulting in beam lifetimes of 100 hours or less with 100 mA stored beam. Significant DC bias levels associated with the presence of stored beam have been observed. These large bias levels are most likely caused by the loss monitor responding to hard x-ray synchrotron radiation. No such response to synchrotron radiation was observed during earlier tests at SSRL. However, the loss monitor response to average stored beam current in APS has provided a reasonable alternative to the DC current transformer (DCCT) for measuring beam lifetimes

  10. Initial results from 50mm short SSC dipoles at Fermilab

    International Nuclear Information System (INIS)

    Bossert, R.C.; Brandt, J.S.; Carson, J.A.; Coulter, K.; Delchamps, S.; Ewald, K.D.; Fulton, H.; Gonczy, I.; Gourlay, S.A.; Jaffery, T.S.; Kinney, W.; Koska, W.; Lamm, M.J.; Strait, J.B.; Wake, M.; Gordon, M.; Hassan, N.; Sims, R.; Winters, M.

    1991-03-01

    Several short model SSC 50 mm bore dipoles are being built and tested at Fermilab. Mechanical design of these magnets has been determined from experience involved in the construction and testing of 40 mm dipoles. Construction experience includes coil winding, curing and measuring, coil end part design and fabrication, ground insulation, instrumentation, collaring and yoke assembly. Fabrication techniques are explained and construction problems are discussed. Similarities and differences from the 40 mm dipole tooling and management components are outlined. Test results from the first models are presented. 19 refs., 12 figs

  11. [Integrated intensive treatment of tinnitus: method and initial results].

    Science.gov (United States)

    Mazurek, B; Georgiewa, P; Seydel, C; Haupt, H; Scherer, H; Klapp, B F; Reisshauer, A

    2005-07-01

    In recent years, no major advances have been made in understanding the mechanisms underlying the development of tinnitus. Hence, the present therapeutic strategies aim at decoupling the subconscious from the perception of tinnitus. Mindful of the lessons drawn from existing tinnitus retraining and desensitisation therapies, a new integrated day hospital strategy of treatment lasting 7-14 days has been developed at the Charité Hospital and is presented in the present paper. The strategy for treating tinnitus in the proximity of patient domicile is designed for patients who feel disturbed in their world of perception and their efficiency due to tinnitus and give evidence of mental and physical strain. In view of the etiologically non-uniform and multiple events connected with tinnitus, consideration was also given to the fact that somatic and psychosocial factors are equally involved. Therefore, therapy should aim at diagnosing and therapeutically influencing those psychosocial factors that reduce the hearing impression to such an extent that the affected persons suffer from strain. The first results of therapy-dependent changes of 46 patients suffering from chronic tinnitus are presented. The data were evaluated before and after 7 days of treatment and 6 months after the end of treatment. Immediately after the treatment, the scores of both the tinnitus questionnaire (Goebel and Hiller) and the subscales improved significantly. These results were maintained during the 6-month post-treatment period and even improved.

  12. New results on initial state & quarkonia with ATLAS

    CERN Document Server

    Tapia Araya, Sebastian; The ATLAS collaboration

    2017-01-01

    Weak bosons do not interact strongly with the dense and hot medium formed in the nuclear collisions, thus should be sensitive to the nuclear modification of parton distribution functions (nPDFs). The in-medium modification of heavy quarkonium states plays an important role in studying the hot and dense medium formed in the larger collision systems. The ATLAS detector, optimized for searching new physics in proton-proton collisions, is especially well equipped to measure Z, W bosons and quakonium in the high occupancy environment produced in heavy-ion collisions. We will present recent results on the Z boson and quarkonia yields as a function of centrality, transverse momentum and rapidity, from the ATLAS experiment.

  13. Overview and initial results of the ETE spherical tokamak

    International Nuclear Information System (INIS)

    Berni, L.A.; Del Bosco, E.; Ferreira, J.G.; Ludwig, G.O.; Oliveira, R.M.; Shibata, C.S.; Barbosa, L.F.F.P.W.; Vilela, W.A.

    2003-01-01

    The ETE spherical tokamak is a small size aspect-ratio machine with major and minor radius of 30 cm and 20 cm, respectively. The vessel was made of Inconel 625 and provides good access for plasma diagnostics through 58 Conflat ports. The first plasma was obtained at the end of 2000 and presently plasma currents of about 45 kA lasting for about 4 ms with electron temperature up to 160 eV and densities of 2.2x10 19 m -3 are routinely obtained. Achievement of the designed parameters for the first phase of operation is expected by the end of this year, with plasma current up to 200 kA lasting for about 15 ms. This paper describes some details of the ETE project, construction and mainly the first results and analysis of basic parameters. (author)

  14. Initial Hubble Diagram Results from the Nearby Supernova Factory

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, S. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France); Aldering, G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Antilogus, P. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France); Aragon, C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Baltay, C. [Yale Univ., New Haven, CT (United States); Bongard, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Buton, C [Inst. of Nuclear Physics of Lyon (France); Childress, M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Copin, Y. [Inst. of Nuclear Physics of Lyon (France); Gangler, E. [Inst. of Nuclear Physics of Lyon (France); Loken, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Nugent, P. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Pain, R. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France); Pecontal, E. [Center of Research Astrophysics of Lyon (CRAL) (France); Pereira, R. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France); Perlmutter, S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rabinowitz, D. [Yale Univ., New Haven, CT (United States); Rigaudier, G. [Center of Research Astrophysics of Lyon (CRAL) (France); Ripoche, P. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France); Runge, K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scalzo, R. [Yale Univ., New Haven, CT (United States); Smadja, G. [Inst. of Nuclear Physics of Lyon (France); Tao, C. [Inst. of Nuclear Physics of Lyon (France); Thomas, R. C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, C. [Lab. Nuclear and High-Energy Physics (LPNHE), Paris (France)

    2017-07-06

    The use of Type Ia supernovae as distance indicators led to the discovery of the accelerating expansion of the universe a decade ago. Now that large second generation surveys have significantly increased the size and quality of the high-redshift sample, the cosmological constraints are limited by the currently available sample of ~50 cosmologically useful nearby supernovae. The Nearby Supernova Factory addresses this problem by discovering nearby supernovae and observing their spectrophotometric time development. Our data sample includes over 2400 spectra from spectral timeseries of 185 supernovae. This talk presents results from a portion of this sample including a Hubble diagram (relative distance vs. redshift) and a description of some analyses using this rich dataset.

  15. Hypoxia-ischemia and retinal ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Charanjit Kaur

    2008-08-01

    Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

  16. Temporo-spatial IMRT optimization: concepts, implementation and initial results

    International Nuclear Information System (INIS)

    Trofimov, Alexei; Rietzel, Eike; Lu Hsiaoming; Martin, Benjamin; Jiang, Steve; Chen, George T Y; Bortfeld, Thomas

    2005-01-01

    With the recent availability of 4D-CT, the accuracy of information on internal organ motion during respiration has improved significantly. We investigate the utility of organ motion information in IMRT treatment planning, using an in-house prototype optimization system. Four approaches are compared: (1) planning with optimized margins, based on motion information; (2) the 'motion kernel' approach, in which a more accurate description of the dose deposit from a pencil beam to a moving target is achieved either through time-weighted averaging of influence matrices, calculated for different instances of anatomy (subsets of 4D-CT data, corresponding to various phases of motion) or through convolution of the pencil beam kernel with the probability density function describing the target motion; (3) optimal gating, or tracking with beam intensity maps optimized independently for each instance of anatomy; and (4) optimal tracking with beam intensity maps optimized simultaneously for all instances of anatomy. The optimization is based on a gradient technique and can handle both physical (dose-volume) and equivalent uniform dose constraints. Optimization requires voxel mapping from phase to phase in order to score the dose in individual voxels as they move. The results show that, compared to the other approaches, margin expansion has a significant disadvantage by substantially increasing the integral dose to patient. While gating or tracking result in the best dose conformation to the target, the former elongates treatment time, and the latter significantly complicates the delivery procedure. The 'motion kernel' approach does not provide a dosimetric advantage, compared to optimal tracking or gating, but might lead to more efficient delivery. A combination of gating with the 'motion kernel' or margin expansion approach will increase the duty cycle and may provide one with the most efficient solution, in terms of complexity of the delivery procedure and dose conformality to

  17. Multi-slice CT urography after diuretic injection: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Nolte-Ernsting, C.C.A.; Wildberger, J.E.; Schmitz-Rode, T.; Guenther, R.W. [Technische Univ. Aachen (Germany). Dept. of Diagnostic Radiology; Borchers, H. [Technische Univ. Aachen (Germany). Dept. of Urology

    2001-03-01

    Purpose: To investigate the feasibility of CT urography (CTU) using a multi-slice (MS) scanner and to find out whether a low-dose diuretic injection is advantageous for the opacification of the urinary tract. Methods: MS-CTU was performed in 21 patients with urologic diseases. In 5/21 patients, 250 ml of physiologic saline solution were injected. In 16/21 patients, 10 mg of furosemide were injected 3-5 min before contrast material administration. A 4x2.5 mm collimation with a pitch of 1.25 and a tube curent of 100-150 mA were used. Scan time was 12-16 sec. 3 mm thin axial images with an overlap of 67% were reconstructed. Multiplanar maximum intensity projection (MIP) images were postprocessed to obtain urographic views. Bone structures were eliminated using the volume-of-interest method. Results: Furosemide-enhanced MS-CTU achieved either near complete or complete opacification in 30/32 (94%) ureters and in 32/32 (100%) pelvicaliceal systems up to a serum creatinine of 150 {mu}mol/l. In our series, only one CTU scan per patient was needed to obtain a diagnostic urogram after 10 min of contrast material injection. Ureteral compression was not necessary. When physiologic saline solution was used instead of furosemide, the radiopacity inside the enhanced pelvicalices was 4-5 times higher and more inhomogeneous. Diuretic-enhanced MS-CTU was more accurate in the depiction of pelvicaliceal details. In combination with furosemide, calculi were well identified inside the opacified urine and were safely differentiated from phleboliths. Postprocessing times of up to 20 minutes were problematic as were contrast-enhanced superimposing bowel loops on MIP images. Conclusion: Preliminary results demonstrate a good feasibility of furosemide-enhanced MS-CTU for obtaining detailed visualization of the entire upper urinary tract. (orig.) [German] Ziel: Untersuchung zur Durchfuehrbarkeit der CT Urographie (CTU) mit einem Multidetektor(MD)-Computertomographen und ob eine

  18. A prototype tap test imaging system: Initial field test results

    Science.gov (United States)

    Peters, J. J.; Barnard, D. J.; Hudelson, N. A.; Simpson, T. S.; Hsu, D. K.

    2000-05-01

    This paper describes a simple, field-worthy tap test imaging system that gives quantitative information about the size, shape, and severity of defects and damages. The system consists of an accelerometer, electronic circuits for conditioning the signal and measuring the impact duration, a laptop PC and data acquisition and processing software. The images are generated manually by tapping on a grid printed on a plastic sheet laid over the part's surface. A mechanized scanner is currently under development. The prototype has produced images for a variety of aircraft composite and metal honeycomb structures containing flaws, damages, and repairs. Images of the local contact stiffness, deduced from the impact duration using a spring model, revealed quantitatively the stiffness reduction due to flaws and damages, as well as the stiffness enhancement due to substructures. The system has been field tested on commercial and military aircraft as well as rotor blades and engine decks on helicopters. Field test results will be shown and the operation of the system will be demonstrated.—This material is based upon work supported by the Federal Aviation Administration under Contract #DTFA03-98-D-00008, Delivery Order No. IA016 and performed at Iowa State University's Center for NDE as part of the Center for Aviation Systems Reliability program.

  19. The Young Solar Analogs Project: Initial Photometric Results

    Science.gov (United States)

    Saken, Jon M.; Gray, R. O.; Corbally, C. J.

    2013-06-01

    Since 2007 we have been conducting spectroscopic monitoring of the Ca II H & K lines and G-band for a sample of 31 YSAs in order to better understand their activity cycles and variations, as well as the effects of young stars on their solar systems. The targets cover the spectral range of stars most likely to contain Earth analogs, F8-K2, and a broad enough range of ages, 0.3 Gyr - 1.5 Gyr, to investigate how activity level changes with stellar age. These studies are already showing possible evidence for activity cycles, large variations in starspot activity, and flaring events. In order to obtain a more complete picture of the nature of the stars' activity and examine the correlations between stellar brightness and chromospheric activity, we have started a complimentary campaign of photometric monitoring of these targets in Johnson B, V, and R, Stromgren v and H-alpha, with the use of a small robotic telescope dedicated to this project. This poster will present some results from the first year of photometric monitoring, focusing on the correlations between the photometric bands, and between the photometric and spectroscopic data, as well as an investigation of short-term (1-2 minutes) spectroscopic variations using data obtained earlier this year on the 1.8 m Vatican Advanced Technology Telescope (VATT).

  20. Interventional C-arm tomosynthesis for vascular imaging: initial results

    Science.gov (United States)

    Langan, David A.; Claus, Bernhard E. H.; Al Assad, Omar; Trousset, Yves; Riddell, Cyril; Avignon, Gregoire; Solomon, Stephen B.; Lai, Hao; Wang, Xin

    2015-03-01

    As percutaneous endovascular procedures address more complex and broader disease states, there is an increasing need for intra-procedure 3D vascular imaging. In this paper, we investigate C-Arm 2-axis tomosynthesis ("Tomo") as an alternative to C-Arm Cone Beam Computed Tomography (CBCT) for workflow situations in which the CBCT acquisition may be inconvenient or prohibited. We report on our experience in performing tomosynthesis acquisitions with a digital angiographic imaging system (GE Healthcare Innova 4100 Angiographic Imaging System, Milwaukee, WI). During a tomo acquisition the detector and tube each orbit on a plane above and below the table respectively. The tomo orbit may be circular or elliptical, and the tomographic half-angle in our studies varied from approximately 16 to 28 degrees as a function of orbit period. The trajectory, geometric calibration, and gantry performance are presented. We overview a multi-resolution iterative reconstruction employing compressed sensing techniques to mitigate artifacts associated with incomplete data reconstructions. In this work, we focus on the reconstruction of small high contrast objects such as iodinated vasculature and interventional devices. We evaluate the overall performance of the acquisition and reconstruction through phantom acquisitions and a swine study. Both tomo and comparable CBCT acquisitions were performed during the swine study thereby enabling the use of CBCT as a reference in the evaluation of tomo vascular imaging. We close with a discussion of potential clinical applications for tomo, reflecting on the imaging and workflow results achieved.

  1. Mars Science Laboratory: Mission, Landing Site, and Initial Results

    Science.gov (United States)

    Grotzinger, John; Blake, D.; Crisp, J.; Edgett, K.; Gellert, R.; Gomez-Elvira, J.; Hassler, D.; Mahaffy, P.; Malin, M.; Meyer, M.; Mitrofanov, I.; Vasavada, A.; Wiens, R.

    2012-10-01

    Scheduled to land on August 5, 2012, the Mars Science Laboratory rover, Curiosity, will conduct an investigation of modern and ancient environments. Recent mission results will be discussed. Curiosity has a lifetime of at least one Mars year ( 23 months), and drive capability of at least 20 km. The MSL science payload was specifically assembled to assess habitability and includes a gas chromatograph-mass spectrometer and gas analyzer that will search for organic carbon in rocks, regolith fines, and the atmosphere; an x-ray diffractometer that will determine mineralogical diversity; focusable cameras that can image landscapes and rock/regolith textures in natural color; an alpha-particle x-ray spectrometer for in situ determination of rock and soil chemistry; a laser-induced breakdown spectrometer to remotely sense the chemical composition of rocks and minerals; an active neutron spectrometer designed to search for water in rocks/regolith; a weather station to measure modern-day environmental variables; and a sensor designed for continuous monitoring of background solar and cosmic radiation. The 155-km diameter Gale Crater was chosen as Curiosity’s field site based on several attributes: an interior mound of ancient flat-lying strata extending almost 5 km above the elevation of the landing site; the lower few hundred meters of the mound show a progression with relative age from clay-bearing to sulfate-bearing strata, separated by an unconformity from overlying likely anhydrous strata; the landing ellipse is characterized by a mixture of alluvial fan and high thermal inertia/high albedo stratified deposits; and a number of stratigraphically/geomorphically distinct fluvial features. Gale’s regional context and strong evidence for a progression through multiple potentially habitable environments, represented by a stratigraphic record of extraordinary extent, insure preservation of a rich record of the environmental history of early Mars.

  2. Initial results from the newborn hearing screening programme in Ireland.

    LENUS (Irish Health Repository)

    O'Connor, A

    2013-03-02

    INTRODUCTION: Hearing screening programmes aim to detect hearing loss in the neonate. The Health Service Executive (HSE) South was the first phase of a national roll-out of a neonatal hearing screening programme in Ireland, going live on 28 April 2011. RESULTS: Over 11,738 babies have been screened for permanent childhood hearing impairment (PCHI) during the first 12 months. The percentage of eligible babies offered hearing screening was 99.2 %. Only 0.2 % (n = 25) of those offered screening declined. 493 (4 %) were referred for immediate diagnostic audiological assessment. The average time between screen and diagnostic audiology appointment was 2 weeks. 15 (1.3\\/1,000) babies have been identified with a PCHI over the 12-month period. 946 (4 %) babies screened were admitted to the neonatal intensive care unit (NICU) for >48 h. The prevalance of PCHI is 7.3\\/1,000 in the NICU population compared to 0.6\\/1000 in the well baby population. 214 (1.8 % of total babies screened) had a clear response in the screening programmes, but were deemed to be at risk of an acquired childhood hearing impairment. These babies will be reassessed with a diagnostic audiology appointment at 8-9 months of age. To date, there is one case of acquired hearing impairment through this targeted follow-up screen. Of the 15 cases of PCHI identified, 8 (53 %) of these had one or more risk factors for hearing loss and 7 (37 %) were admitted to the NICU for >48 h. Four babies were referred for assessment at the National Cochlear Implant Centre.

  3. Changes in science classrooms resulting from collaborative action research initiatives

    Science.gov (United States)

    Oh, Phil Seok

    Collaborative action research was undertaken over two years between a Korean science teacher and science education researchers at the University of Iowa. For the purpose of realizing science learning as envisioned by constructivist principles, Group-Investigations were implemented three or five times per project year. In addition, the second year project enacted Peer Assessments among students. Student perceptions of their science classrooms, as measured by the Constructivist Learning Environment Survey (CLES), provided evidence that the collaborative action research was successful in creating constructivist learning environments. Student attitudes toward science lessons, as examined by the Enjoyment of Science Lessons Scale (ESLS), indicated that the action research also contributed to developing more positive attitudes of students about science learning. Discourse analysis was conducted on video-recordings of in-class presentations and discussions. The results indicated that students in science classrooms which were moving toward constructivist learning environments engaged in such discursive practices as: (1) Communicating their inquiries to others, (2) Seeking and providing information through dialogues, and (3) Negotiating conflicts in their knowledge and beliefs. Based on these practices, science learning was viewed as the process of constructing knowledge and understanding of science as well as the process of engaging in scientific inquiry and discourse. The teacher's discursive practices included: (1) Wrapping up student presentations, (2) Addressing misconceptions, (3) Answering student queries, (4) Coaching, (5) Assessing and advising, (6) Guiding students discursively into new knowledge, and (7) Scaffolding. Science teaching was defined as situated acts of the teacher to facilitate the learning process. In particular, when the classrooms became more constructivist, the teacher intervened more frequently and carefully in student activities to fulfill a

  4. [Initial results of the Erfurt Prevention of Prematurity Campaign].

    Science.gov (United States)

    Hoyme, U B; Grosch, A; Roemer, V M; Saling, E

    1998-01-01

    identification of women at risk for prematurity. Earliest possible intervention by the obstetrician appears to result in reducing the rate of prematures and in particular of very early prematures (< 32 + 0 weeks).

  5. Lesion insertion in the projection domain: Methods and initial results

    International Nuclear Information System (INIS)

    Chen, Baiyu; Leng, Shuai; Yu, Lifeng; Yu, Zhicong; Ma, Chi; McCollough, Cynthia

    2015-01-01

    Purpose: To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way of achieving this objective is to create hybrid images that combine patient images with inserted lesions. Because conventional hybrid images generated in the image domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection-domain approach. Methods: Lesions were segmented from patient images and forward projected to acquire lesion projections. The forward-projection geometry was designed according to a commercial CT scanner and accommodated both axial and helical modes with various focal spot movement patterns. The energy employed by the commercial CT scanner for beam hardening correction was measured and used for the forward projection. The lesion projections were inserted into patient projections decoded from commercial CT projection data. The combined projections were formatted to match those of commercial CT raw data, loaded onto a commercial CT scanner, and reconstructed to create the hybrid images. Two validations were performed. First, to validate the accuracy of the forward-projection geometry, images were reconstructed from the forward projections of a virtual ACR phantom and compared to physically acquired ACR phantom images in terms of CT number accuracy and high-contrast resolution. Second, to validate the realism of the lesion in hybrid images, liver lesions were segmented from patient images and inserted back into the same patients, each at a new location specified by a radiologist. The inserted lesions were compared to the original lesions and visually assessed for realism by two experienced radiologists in a blinded fashion. Results: For the validation of the forward-projection geometry, the images reconstructed from the forward projections of the virtual ACR phantom were consistent with the images physically

  6. Lesion insertion in the projection domain: Methods and initial results

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Baiyu; Leng, Shuai; Yu, Lifeng; Yu, Zhicong; Ma, Chi; McCollough, Cynthia, E-mail: mccollough.cynthia@mayo.edu [Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2015-12-15

    Purpose: To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way of achieving this objective is to create hybrid images that combine patient images with inserted lesions. Because conventional hybrid images generated in the image domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection-domain approach. Methods: Lesions were segmented from patient images and forward projected to acquire lesion projections. The forward-projection geometry was designed according to a commercial CT scanner and accommodated both axial and helical modes with various focal spot movement patterns. The energy employed by the commercial CT scanner for beam hardening correction was measured and used for the forward projection. The lesion projections were inserted into patient projections decoded from commercial CT projection data. The combined projections were formatted to match those of commercial CT raw data, loaded onto a commercial CT scanner, and reconstructed to create the hybrid images. Two validations were performed. First, to validate the accuracy of the forward-projection geometry, images were reconstructed from the forward projections of a virtual ACR phantom and compared to physically acquired ACR phantom images in terms of CT number accuracy and high-contrast resolution. Second, to validate the realism of the lesion in hybrid images, liver lesions were segmented from patient images and inserted back into the same patients, each at a new location specified by a radiologist. The inserted lesions were compared to the original lesions and visually assessed for realism by two experienced radiologists in a blinded fashion. Results: For the validation of the forward-projection geometry, the images reconstructed from the forward projections of the virtual ACR phantom were consistent with the images physically

  7. Experimental data suggesting that inflammation mediated rat liver mitochondrial dysfunction results from secondary hypoxia rather than from direct effects of inflammatory mediators

    Directory of Open Access Journals (Sweden)

    Adelheid eWeidinger

    2013-06-01

    Full Text Available Systemic inflammatory response (SIR comprises direct effects of inflammatory mediators (IM and indirect effects, such as secondary circulatory failure which results in tissue hypoxia (HOX. These two key components, SIR and HOX, cause multiple organ failure (MOF. Since HOX and IM occur and interact simultaneously in vivo, it is difficult to clarify their individual pathological impact. To eliminate this interaction, precision cut liver slices (PCLS were used in this study aiming to dissect the effects of HOX and IM on mitochondrial function, integrity of cellular membrane and the expression of genes associated with inflammation. HOX was induced by incubating PCLS or rat liver mitochondria at pO2<1% followed by reoxygenation (HOX/ROX model. Inflammatory injury was stimulated by incubating PCLS with IM (IM model. We found upregulation of inducible nitric oxide synthase (iNOS expression only in the IM model, while heme oxygenase 1 (HO-1 expression was upregulated only in the HOX/ROX model. Elevated expression of interleukin 6 (IL-6 was found in both models reflecting converging pathways regulating the expression of this gene. Both models caused damage to hepatocytes resulting in the release of alanine aminotransferase (ALT. The leakage of aspartate aminotransferase (AST was observed only during the hypoxic phase in the HOX/ROX model. The reoxygenation phase of HOX, but not IM, drastically impaired mitochondrial electron supply via complex I and II. Additional experiments performed with isolated mitochondria showed that free iron, released during HOX, is likely a key prerequisite of mitochondrial dysfunction induced during the reoxygenation phase. Our data suggests that mitochondrial dysfunction, previously observed in in vivo SIR-models is the result of secondary circulatory failure inducing HOX rather than the result of a direct interaction of IM with liver cells.

  8. Induction of erythropoiesis by hypoxia-inducible factor prolyl hydroxylase inhibitors without promotion of tumor initiation, progression, or metastasis in a VEGF-sensitive model of spontaneous breast cancer

    Science.gov (United States)

    Seeley, Todd W; Sternlicht, Mark D; Klaus, Stephen J; Neff, Thomas B; Liu, David Y

    2017-01-01

    The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neundl-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592). In NeuYD mice, HIF-PHI treatments elevated erythropoiesis markers, but no differences were detected in tumor onset or the phenotypes of established tumors. PMID:28331872

  9. Migraine induced by hypoxia

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2016-01-01

    in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three...... and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P ... suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated....

  10. Selective vulnerability in brain hypoxia

    DEFF Research Database (Denmark)

    Cervos-Navarro, J.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis......Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis...

  11. Hepcidin: A Critical Regulator of Iron Metabolism during Hypoxia

    Directory of Open Access Journals (Sweden)

    Korry J. Hintze

    2011-01-01

    Full Text Available Iron status affects cognitive and physical performance in humans. Recent evidence indicates that iron balance is a tightly regulated process affected by a series of factors other than diet, to include hypoxia. Hypoxia has profound effects on iron absorption and results in increased iron acquisition and erythropoiesis when humans move from sea level to altitude. The effects of hypoxia on iron balance have been attributed to hepcidin, a central regulator of iron homeostasis. This paper will focus on the molecular mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF/hypoxia response element (HRE system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may affect hepcidin signaling and organismal iron metabolism.

  12. Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

    Science.gov (United States)

    Stokes, Jennifer A; Arbogast, Tara E; Moya, Esteban A; Fu, Zhenxing; Powell, Frank L

    2017-04-01

    Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, Pi O 2  = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly ( P minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia. NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti-inflammatory properties, also blocks astrocyte activation in respiratory

  13. Body temperature depression and peripheral heat loss accompany the metabolic and ventilatory responses to hypoxia in low and high altitude birds.

    Science.gov (United States)

    Scott, Graham R; Cadena, Viviana; Tattersall, Glenn J; Milsom, William K

    2008-04-01

    The objectives of this study were to compare the thermoregulatory, metabolic and ventilatory responses to hypoxia of the high altitude bar-headed goose with low altitude waterfowl. All birds were found to reduce body temperature (T(b)) during hypoxia, by up to 1-1.5 degrees C in severe hypoxia. During prolonged hypoxia, T(b) stabilized at a new lower temperature. A regulated increase in heat loss contributed to T(b) depression as reflected by increases in bill surface temperatures (up to 5 degrees C) during hypoxia. Bill warming required peripheral chemoreceptor inputs, since vagotomy abolished this response to hypoxia. T(b) depression could still occur without bill warming, however, because vagotomized birds reduced T(b) as much as intact birds. Compared to both greylag geese and pekin ducks, bar-headed geese required more severe hypoxia to initiate T(b) depression and heat loss from the bill. However, when T(b) depression or bill warming were expressed relative to arterial O(2) concentration (rather than inspired O(2)) all species were similar; this suggests that enhanced O(2) loading, rather than differences in thermoregulatory control centres, reduces T(b) depression during hypoxia in bar-headed geese. Correspondingly, bar-headed geese maintained higher rates of metabolism during severe hypoxia (7% inspired O(2)), but this was only partly due to differences in T(b). Time domains of the hypoxic ventilatory response also appeared to differ between bar-headed geese and low altitude species. Overall, our results suggest that birds can adjust peripheral heat dissipation to facilitate T(b) depression during hypoxia, and that bar-headed geese minimize T(b) and metabolic depression as a result of evolutionary adaptations that enhance O(2) transport.

  14. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

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    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

    2013-12-01

    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  15. The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis.

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    Welsh, Sarah J; Bellamy, William T; Briehl, Margaret M; Powis, Garth

    2002-09-01

    Hypoxia-inducible factor 1 (HIF-1), a heterodimer of HIF-1alpha and HIF-1beta subunits, is a transcriptional activator central to the cellular response to low oxygen that includes metabolic adaptation, angiogenesis, metastasis, and inhibited apoptosis. Thioredoxin-1 (Trx-1) is a small redox protein overexpressed in a number of human primary tumors. We have examined the effects of Trx-1 on HIF activity and the activation of downstream genes. Stable transfection of human breast carcinoma MCF-7 cells with human Trx-1 caused a significant increase in HIF-1alpha protein levels under both normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. Trx-1 increased hypoxia-induced HIF-1 transactivation activity measured using a luciferase reporter under the control of the hypoxia response element. Changes in HIF-1alpha mRNA levels did not account for the changes observed at the protein level, and HIF-1beta protein levels did not change. Trx-1 transfection also caused a significant increase in the protein products of hypoxia-responsive genes, including vascular endothelial growth factor (VEGF) and nitric oxide synthase 2 in a number of different cell lines (MCF-7 human breast and HT29 human colon carcinomas and WEHI7.2 mouse lymphoma cells) under both normoxic and hypoxic conditions. The pattern of expression of the different isoforms of VEGF was not changed by Trx-1. Transfection of a redox-inactive Trx-1 (C32S/C35S) markedly decreased levels of HIF-1alpha protein, HIF-1 transactivating activity, and VEGF protein in MCF-7 cells compared with empty vector controls. In vivo studies using WEHI7.2 cells transfected with Trx-1 showed significantly increased tumor VEGF and angiogenesis. The results suggest that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF production and tumor angiogenesis.

  16. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

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    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

    2017-05-01

    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  17. Redox signaling during hypoxia in mammalian cells

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    Kimberly A. Smith

    2017-10-01

    Full Text Available Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS such as hydrogen peroxide (H2O2 occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(PH oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

  18. Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea.

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    El-Chami, Mohamad; Sudan, Sukhesh; Lin, Ho-Sheng; Mateika, Jason H

    2017-10-01

    Our purpose was to determine whether exposure to mild intermittent hypoxia leads to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events. Ten male participants were treated with twelve 2-min episodes of hypoxia ([Formula: see text] ≈50 mmHg) separated by 2-min intervals of normoxia in the presence of [Formula: see text] that was sustained 3 mmHg above baseline. During recovery from the last episode, the positive airway pressure was reduced in a stepwise fashion until flow limitation was evident. The participants also completed a sham protocol under normocapnic conditions, which mimicked the time frame of the intermittent hypoxia protocol. After exposure to intermittent hypoxia, the therapeutic pressure was significantly reduced (i.e., 5 cmH 2 O) without evidence of flow limitation (103.4 ± 6.3% of baseline, P = 0.5) or increases in upper airway resistance (95.6 ± 15.0% of baseline, P = 0.6). In contrast, a similar decrease in pressure was accompanied by flow limitation (77.0 ± 1.8% of baseline, P = 0.001) and an increase in upper airway resistance (167.2 ± 17.5% of baseline, P = 0.01) after the sham protocol. Consistent with the initiation of long-term facilitation of upper airway muscle activity, exposure to intermittent hypoxia reduced the therapeutic pressure required to eliminate apneic events that could improve treatment compliance. This possibility, coupled with the potentially beneficial effects of intermittent hypoxia on comorbidities linked to sleep apnea, suggests that mild intermittent hypoxia may have a multipronged therapeutic effect on sleep apnea. NEW & NOTEWORTHY Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent with previous results, which have shown that long-term facilitation of upper muscle activity can be initiated following exposure to intermittent hypoxia in humans.

  19. Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α and Toll-Like Receptor 4 (TLR4 Overexpression in a Porcine Model.

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    Zhiyong Zhang

    Full Text Available Ischemia/reperfusion (I/R during partial nephrectomy (PN contributes to acute kidney injury (AKI, which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α and toll-like receptor 4 (TLR4, within kidney tissue and peripheral blood leukocytes (PBL in a porcine model of PN.Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0, every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed.Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30-60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation.In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted.

  20. Cycling hypoxia: A key feature of the tumor microenvironment.

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    Michiels, Carine; Tellier, Céline; Feron, Olivier

    2016-08-01

    A compelling body of evidence indicates that most human solid tumors contain hypoxic areas. Hypoxia is the consequence not only of the chaotic proliferation of cancer cells that places them at distance from the nearest capillary but also of the abnormal structure of the new vasculature network resulting in transient blood flow. Hence two types of hypoxia are observed in tumors: chronic and cycling (intermittent) hypoxia. Most of the current work aims at understanding the role of chronic hypoxia in tumor growth, response to treatment and metastasis. Only recently, cycling hypoxia, with spatial and temporal fluctuations in oxygen levels, has emerged as another key feature of the tumor environment that triggers different responses in comparison to chronic hypoxia. Either type of hypoxia is associated with distinct effects not only in cancer cells but also in stromal cells. In particular, cycling hypoxia has been demonstrated to favor, to a higher extent than chronic hypoxia, angiogenesis, resistance to anti-cancer treatments, intratumoral inflammation and tumor metastasis. These review details these effects as well as the signaling pathway it triggers to switch on specific transcriptomic programs. Understanding the signaling pathways through which cycling hypoxia induces these processes that support the development of an aggressive cancer could convey to the emergence of promising new cancer treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism.

    Science.gov (United States)

    Eltzschig, Holger K; Thompson, Linda F; Karhausen, Jorn; Cotta, Richard J; Ibla, Juan C; Robson, Simon C; Colgan, Sean P

    2004-12-15

    Hypoxia is a well-documented inflammatory stimulus and results in tissue polymorphonuclear leukocyte (PMN) accumulation. Likewise, increased tissue adenosine levels are commonly associated with hypoxia, and given the anti-inflammatory properties of adenosine, we hypothesized that adenosine production via adenine nucleotide metabolism at the vascular surface triggers an endogenous anti-inflammatory response during hypoxia. Initial in vitro studies indicated that endogenously generated adenosine, through activation of PMN adenosine A(2A) and A(2B) receptors, functions as an antiadhesive signal for PMN binding to microvascular endothelia. Intravascular nucleotides released by inflammatory cells undergo phosphohydrolysis via hypoxia-induced CD39 ectoapyrase (CD39 converts adenosine triphosphate/adenosine diphosphate [ATP/ADP] to adenosine monophosphate [AMP]) and CD73 ecto-5'-nucleotidase (CD73 converts AMP to adenosine). Extensions of our in vitro findings using cd39- and cd73-null animals revealed that extracellular adenosine produced through adenine nucleotide metabolism during hypoxia is a potent anti-inflammatory signal for PMNs in vivo. These findings identify CD39 and CD73 as critical control points for endogenous adenosine generation and implicate this pathway as an innate mechanism to attenuate excessive tissue PMN accumulation.

  2. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

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    Yoichi Takakusagi

    Full Text Available BACKGROUND: TH-302 is a hypoxia-activated prodrug (HAP of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. METHODOLOGY/RESULTS: The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2, with minimal effect under aerobic conditions (21% O2. Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3. Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3, significantly delayed tumor growth. CONCLUSIONS/SIGNIFICANCE: Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the

  3. Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

    Science.gov (United States)

    Conkin, J.; Wessel, J. H., III

    2011-01-01

    INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

  4. HPV E6 and E7 in hypoxia mediated tumorigenesis in cervical epithelial cells

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell; Graeber, Thomas G.; Peehl, Donna M.; Giaccia, Amato J.

    1996-01-01

    Objective: In our previous work, we found that hypoxia induces apoptosis in oncogenically transformed rodent cells and loss of the p53 tumor suppressor gene significantly reduces hypoxia induced cell death. In this report, we show that transformation of wild-type p53 expressing primary cervical epithelial cells with the E6 and E7 genes from high risk human papillomavirus (HPV) type 16 dramatically enhances their susceptibility to hypoxia induced apoptosis. Materials and Methods: Sub confluent primary normal human cervical epithelial cells and normal human fibroblasts were infected with retroviral vectors containing HPV16 E6 and E7 and the neomycin selectable marker using previously described techniques. Clones were selected and isolated in neomycin containing media. Exponentially growing cells were treated with hypoxia (0.02% O 2 ) using specially designed chambers, irradiated (800 cGy) using a cesium source, or grown under aerobic conditions (20% O 2 ) as a control. After treatment, cells were stained with Hoescht and propidium iodide and viewed with a fluorescent microscope for analysis of apoptotic cells. To determine increase in expression of p53, immuno blots were performed using whole cell extracts. Results: After a 48 hour exposure to hypoxic conditions, 40% of E6 and E7 transformed cervical cells exhibit morphologic features indicative of apoptosis, compared to 5% of untransformed cervical cells. Exposure of HPV E6 and E7 transformed cells to ionizing radiation, however, did not initiate apoptosis. Immunoblot assays show induction of p53 under hypoxic conditions but not by ionizing radiation, indicating that hypoxia is able to induce p53 in the presence of E6 and that hypoxia activates p53 by a pathway which is distinct from that of ionizing radiation. Furthermore, hypoxia did not induce apoptosis in normal human fibroblasts transformed with E6 and E7, suggesting that the cellular response to hypoxia is influenced by the cell type. Conclusion: These results

  5. Analysis of hypoxia and hypoxia-like states through metabolite profiling.

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    Julie E Gleason

    Full Text Available In diverse organisms, adaptation to low oxygen (hypoxia is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress.

  6. Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

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    Pei Wang

    2013-09-01

    Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

  7. Self-initiated actions result in suppressed auditory but amplified visual evoked components in healthy participants.

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    Mifsud, Nathan G; Oestreich, Lena K L; Jack, Bradley N; Ford, Judith M; Roach, Brian J; Mathalon, Daniel H; Whitford, Thomas J

    2016-05-01

    Self-suppression refers to the phenomenon that sensations initiated by our own movements are typically less salient, and elicit an attenuated neural response, compared to sensations resulting from changes in the external world. Evidence for self-suppression is provided by previous ERP studies in the auditory modality, which have found that healthy participants typically exhibit a reduced auditory N1 component when auditory stimuli are self-initiated as opposed to externally initiated. However, the literature investigating self-suppression in the visual modality is sparse, with mixed findings and experimental protocols. An EEG study was conducted to expand our understanding of self-suppression across different sensory modalities. Healthy participants experienced either an auditory (tone) or visual (pattern-reversal) stimulus following a willed button press (self-initiated), a random interval (externally initiated, unpredictable onset), or a visual countdown (externally initiated, predictable onset-to match the intrinsic predictability of self-initiated stimuli), while EEG was continuously recorded. Reduced N1 amplitudes for self- versus externally initiated tones indicated that self-suppression occurred in the auditory domain. In contrast, the visual N145 component was amplified for self- versus externally initiated pattern reversals. Externally initiated conditions did not differ as a function of their predictability. These findings highlight a difference in sensory processing of self-initiated stimuli across modalities, and may have implications for clinical disorders that are ostensibly associated with abnormal self-suppression. © 2016 Society for Psychophysiological Research.

  8. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

    International Nuclear Information System (INIS)

    Vordermark, D.; Brown, J.M.

    2003-01-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1α responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1α overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a benefit from specific hypoxia

  9. Effects of hypoxia and hypercapnia on geniohyoid contractility and endurance.

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    Salmone, R J; Van Lunteren, E

    1991-08-01

    Sleep apnea and other respiratory diseases produce hypoxemia and hypercapnia, factors that adversely affect skeletal muscle performance. To examine the effects of these chemical alterations on force production by an upper airway dilator muscle, the contractile and endurance characteristics of the geniohyoid muscle were examined in situ during severe hypoxia (arterial PO2 less than 40 Torr), mild hypoxia (PO2 45-65 Torr), and hypercapnia (PCO2 55-80 Torr) and compared with hyperoxic-normocapnic conditions in anesthetized cats. Muscles were studied at optimal length, and contractile force was assessed in response to supramaximal electrical stimulation of the hypoglossal nerve (n = 7 cats) or geniohyoid muscle (n = 2 cats). There were no significant changes in the twitch kinetics or force-frequency curve of the geniohyoid muscle during hypoxia or hypercapnia. However, the endurance of the geniohyoid, as reflected in the fatigue index (ratio of force at 2 min to initial force in response to 40-Hz stimulation at a duty cycle 0.33), was significantly reduced by severe hypoxia but not by hypercapnia or mild hypoxia. In addition, the downward shift in the force-frequency curve after the repetitive stimulation protocol was greater during hypoxia than hyperoxia, especially at higher frequencies. In conclusion, the ability of the geniohyoid muscle to maintain force output during high levels of activation is adversely affected by severe hypoxia but not mild hypoxia or hypercapnia. However, none of these chemical perturbations affected muscle contractility acutely.

  10. Fractional Differential Equations in Terms of Comparison Results and Lyapunov Stability with Initial Time Difference

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    Coşkun Yakar

    2010-01-01

    Full Text Available The qualitative behavior of a perturbed fractional-order differential equation with Caputo's derivative that differs in initial position and initial time with respect to the unperturbed fractional-order differential equation with Caputo's derivative has been investigated. We compare the classical notion of stability to the notion of initial time difference stability for fractional-order differential equations in Caputo's sense. We present a comparison result which again gives the null solution a central role in the comparison fractional-order differential equation when establishing initial time difference stability of the perturbed fractional-order differential equation with respect to the unperturbed fractional-order differential equation.

  11. A Community-Level Initiative to Prevent Obesity: Results From Kaiser Permanente's Healthy Eating Active Living Zones Initiative in California.

    Science.gov (United States)

    Cheadle, Allen; Atiedu, Akpene; Rauzon, Suzanne; Schwartz, Pamela M; Keene, Laura; Davoudi, Mehrnaz; Spring, Rebecca; Molina, Michelle; Lee, Lynda; Boyle, Kathryn; Williamson, Dana; Steimberg, Clara; Tinajero, Roberta; Ravel, Jodi; Nudelman, Jean; Azuma, Andrea Misako; Kuo, Elena S; Solomon, Loel

    2018-05-01

    A growing number of health systems are leading health promotion efforts in their wider communities. What impact are these efforts having on health behaviors and ultimately health status? This paper presents evaluation results from the place-based Kaiser Permanente Healthy Eating Active Living Zones obesity prevention initiative, implemented in 2011-2015 in 12 low-income communities in Kaiser Permanente's Northern and Southern California Regions. The Healthy Eating Active Living Zones design targeted places and people through policy, environmental, and programmatic strategies. Each Healthy Eating Active Living Zone is a small, low-income community of 10,000 to 20,000 residents with high obesity rates and other health disparities. Community coalitions planned and implemented strategies in each community. A population-dose approach and pre and post surveys were used to assess impact of policy, program, and environmental change strategies; the analysis was conducted in 2016. Population dose is the product of reach (number of people affected by a strategy divided by target population size) and strength (the effect size or relative change in behavior for each person exposed to the strategy). More than 230 community change strategies were implemented over 3 years, encompassing policy, environmental, and programmatic changes as well as efforts to build community capacity to sustain strategies and make changes in the future. Positive population-level results were seen for higher-dose strategies, particularly those targeting youth physical activity. Higher-dose strategies were more likely to be found in communities with the longest duration of investment. These results demonstrate that strong (high-dose), community-based obesity prevention strategies can lead to improved health behaviors, particularly among youth in school settings. This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is

  12. Hypoxic hypoxia as a means of modifying radiosensibility

    International Nuclear Information System (INIS)

    Neumeister, K.; Niemiec, C.; Bolck, M.; Jahns, J.; Kamprad, F.; Arnold, P.; Johannsen, U.; Koch, F.; Mehlhorn, G.

    1977-01-01

    Following an overview of the various possibilities of creating hypoxia in mammals, the problem of reducing radioresistance of hypoxic tumor cells is treated. Furthermore, the results of irradiation experiments with mice, rats and pigs breathing hypoxic mixtures of O 2 and N 2 are given and discussed with a view to applying hypoxic hypoxia in the radiotherapy of human tumors. (author)

  13. Role of hypoxia and hypoxia inducible factor in physiological and pathological conditions

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    Mozhgan Jahani

    2017-11-01

    Full Text Available Introduction: Organisms are exposed to oxygen deprivation (Hypoxia in various physiological and pathological conditions. There are different conserve evolutionary responses to counterview with this stress that primary transcriptional response to stress related to hypoxia is interceded by hypoxia-inducible factor (HIF-1 in mammals. This factor can regulate different genes that have essential roles in adaptation to this condition. In this review, the role of this factor in physiological and pathological conditions under hypoxic condition has been evaluated after examining structural features and regulation characteristics of HIF-1. Methods: First, articles related to the keywords of hypoxia and HIF-1 (from 1991-2016 were searched from valid databases such as Springer Link, Google Scholar, PubMed and Science direct. Then, the articles correlated with hypoxia, HIF-1 and their roles in physiological and pathological conditions (120 articles were searched and just 64 articles were selected for this study. Result: According to studies, there are different genes in cells and organs that can be regulated by HIF-1. Activation of genes expression by this protein occurs through its linkage to cis-acting of 50 base pair hypoxia response element (HRE region located in their promotor and enhancer. Depending on circumstances, activation of these genes can be beneficial or harmful. Conclusion: Activation of different genes in hypoxia by HIF-1 has different effects on physiological and pathological conditions. Therefore, HIF-1, as a hypoxia-inducible factor in hypoxic conditions, plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen.

  14. Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

    Directory of Open Access Journals (Sweden)

    Adolf M. Sandbichler

    2018-04-01

    of oxidized peroxiredoxins, resulting in a highly oxidized nocturnal cellular environment. Of note, circadian rhythms of cytosolic H2O2 remain unaltered, while the transcriptional clock is already attenuated, as it is known to occur also under chronic hypoxia. Conclusion: We therefor propose that the realignment of metabolic redox oscillations might initiate the observed hypoxia induced attenuation of the transcriptional clock, based on the reduced binding affinity of the CLOCK/BMAL complex to the DNA in an oxidized environment.

  15. Initial results from a charge exchange q-diagnostic on TEXT-U

    International Nuclear Information System (INIS)

    Valanju, P.M.; Duraiappah, L.; Bengtson, R.D.; Karzhavin, Y.; Nikitin, A.

    1994-01-01

    The authors present initial results from a new q-diagnostic for TEXT-Upgrade. This method is based on using a toroidal array of detectors to determine the plane in which beam-injected neutrals are emitted after two charge-exchange collisions. The potential advantages are low cost, full plasma accessibility, and good time resolution. Their initial series of experiments on TEXT-U established the feasibility of this technique

  16. p53 dependent apoptotic cell death induces embryonic malformation in Carassius auratus under chronic hypoxia.

    Directory of Open Access Journals (Sweden)

    Paramita Banerjee Sawant

    Full Text Available Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD, leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the anti-apoptotic Bcl-2 during the initial 12 hours post fertilization (hpf and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD, ultimately resulting in significant (p<0.05 embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos.

  17. Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells.

    Science.gov (United States)

    Sandbichler, Adolf M; Jansen, Bianca; Peer, Bettina A; Paulitsch, Monika; Pelster, Bernd; Egg, Margit

    2018-01-01

    Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly

  18. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    Science.gov (United States)

    Chandel, N. S.; Maltepe, E.; Goldwasser, E.; Mathieu, C. E.; Simon, M. C.; Schumacker, P. T.

    1998-09-01

    Transcriptional activation of erythropoietin, glycolytic enzymes, and vascular endothelial growth factor occurs during hypoxia or in response to cobalt chloride (CoCl2) in Hep3B cells. However, neither the mechanism of cellular O2 sensing nor that of cobalt is fully understood. We tested whether mitochondria act as O2 sensors during hypoxia and whether hypoxia and cobalt activate transcription by increasing generation of reactive oxygen species (ROS). Results show (i) wild-type Hep3B cells increase ROS generation during hypoxia (1.5% O2) or CoCl2 incubation, (ii) Hep3B cells depleted of mitochondrial DNA (ρ 0 cells) fail to respire, fail to activate mRNA for erythropoietin, glycolytic enzymes, or vascular endothelial growth factor during hypoxia, and fail to increase ROS generation during hypoxia; (iii) ρ 0 cells increase ROS generation in response to CoCl2 and retain the ability to induce expression of these genes; and (iv) the antioxidants pyrrolidine dithiocarbamate and ebselen abolish transcriptional activation of these genes during hypoxia or CoCl2 in wild-type cells, and abolish the response to CoCl2 in ρ 0 cells. Thus, hypoxia activates transcription via a mitochondria-dependent signaling process involving increased ROS, whereas CoCl2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism.

  19. Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and tumor biology

    International Nuclear Information System (INIS)

    Varia, Mahesh A.; Kennedy, Andrew S.; Calkins-Adams, Dennise P.; Rinker, Lillian; Novotny, Debra; Fowler, Wesley C.; Raleigh, James A.

    1997-01-01

    Purpose/Objectives: Tumor hypoxia appears to be associated with treatment resistance and with gene expression that may lead to hypoxia-mediated selection of tumor cells as a source for cell growth and metastases. The objective of this study was to develop complementary techniques of hypoxia detection with molecular markers of cell proliferation and metastases in order to investigate the role of tumor hypoxia in tumor biology. Materials and Methods: Pimonidazole is a 2-nitroimidazole which is reductively-activated and becomes covalently bound to thiol-containing proteins only in hypoxic cells. These adducts can be detected using immunohistochemistry, enzyme linked immunosorbent assay or flow cytometry as a measure of hypoxia in tumors. Quantitative immunohistochemical analysis has been completed for five patients with squamous cell carcinoma of the cervix who were given pimonidazole hydrochloride (0.5 g/m 2 intravenously) followed by cervical biopsies 24 hours later. Informed consent was obtained according to a protocol approved by the Institutional Review Board. A minimum of 3 random biopsies were obtained from the tumors and at least four sections examined from each biopsy site. Formalin fixed, paraffin embedded tissue sections were immunostained for pimonidazole binding using a mouse monoclonal antibody. Commercially available monoclonal antibodies were used to detect cell proliferation markers MIB-1 (Ki-67) and to detect vascular endothelial growth factor (VEGF) in tumor cells in contiguous sections. The extent of immunostaining was expressed as the percent of immunostained to total tumor cells as determined by Chalkley point counting. Results: No clinical toxicities were associated with pimonidazole infusion. Immunostaining with pimonidazole antibody was observed in all patients indicating the presence of tumor hypoxia. Qualitatively there is little or no overlap between the areas of hypoxia and proliferation. Quantitative data tabulated below show the

  20. A Large-Scale Initiative Inviting Patients to Share Personal Fitness Tracker Data with Their Providers: Initial Results.

    Directory of Open Access Journals (Sweden)

    Joshua M Pevnick

    Full Text Available Personal fitness trackers (PFT have substantial potential to improve healthcare.To quantify and characterize early adopters who shared their PFT data with providers.We used bivariate statistics and logistic regression to compare patients who shared any PFT data vs. patients who did not.A patient portal was used to invite 79,953 registered portal users to share their data. Of 66,105 users included in our analysis, 499 (0.8% uploaded data during an initial 37-day study period. Bivariate and regression analysis showed that early adopters were more likely than non-adopters to be younger, male, white, health system employees, and to have higher BMIs. Neither comorbidities nor utilization predicted adoption.Our results demonstrate that patients had little intrinsic desire to share PFT data with their providers, and suggest that patients most at risk for poor health outcomes are least likely to share PFT data. Marketing, incentives, and/or cultural change may be needed to induce such data-sharing.

  1. Quality initiatives: improving patient flow for a bone densitometry practice: results from a Mayo Clinic radiology quality initiative.

    Science.gov (United States)

    Aakre, Kenneth T; Valley, Timothy B; O'Connor, Michael K

    2010-03-01

    Lean Six Sigma process improvement methodologies have been used in manufacturing for some time. However, Lean Six Sigma process improvement methodologies also are applicable to radiology as a way to identify opportunities for improvement in patient care delivery settings. A multidisciplinary team of physicians and staff conducted a 100-day quality improvement project with the guidance of a quality advisor. By using the framework of DMAIC (define, measure, analyze, improve, and control), time studies were performed for all aspects of patient and technologist involvement. From these studies, value stream maps for the current state and for the future were developed, and tests of change were implemented. Comprehensive value stream maps showed that before implementation of process changes, an average time of 20.95 minutes was required for completion of a bone densitometry study. Two process changes (ie, tests of change) were undertaken. First, the location for completion of a patient assessment form was moved from inside the imaging room to the waiting area, enabling patients to complete the form while waiting for the technologist. Second, the patient was instructed to sit in a waiting area immediately outside the imaging rooms, rather than in the main reception area, which is far removed from the imaging area. Realignment of these process steps, with reduced technologist travel distances, resulted in a 3-minute average decrease in the patient cycle time. This represented a 15% reduction in the initial patient cycle time with no change in staff or costs. Radiology process improvement projects can yield positive results despite small incremental changes.

  2. Mechanisms Causing Hypoxia in the Baltic Sea at Different Spatial and Temporal Scales

    Science.gov (United States)

    Conley, D. J.; Carstensen, J.; Gustafsson, B.; Slomp, C. P.

    2016-02-01

    A number of synthesis efforts have documented the world-wide increase in hypoxia, which is primarily driven by nutrient inputs with consequent organic matter enrichment. Physical factors including freshwater or saltwater inputs, stratification and temperature also play an important role in causing and sustaining hypoxia. The Baltic Sea provides an interesting case study to examine changes in oxygen dynamics over time because of the diversity of the types of hypoxia that occur, which ranges from episodic to seasonal hypoxia to perennial hypoxia. Hypoxia varies spatially across the basin with differences between open water bottoms and coastal systems. In addition, the extent and intensity of hypoxia has also varied greatly over the history of the basin, e.g. the last 8000 years. We will examine the mechanisms causing hypoxia at different spatial and temporal scales. The hydrodynamical setting is an important governing factor controlling possible time scales of hypoxia, but enhanced nutrient fluxes and global warming amplify oxygen depletion when oxygen supply by physical processes cannot meet oxygen demands from respiration. Our results indicate that climate change is counteracting management efforts to reduce hypoxia. We will address how hypoxia in the Baltic Sea is terminated at different scales. More importantly, we will explore the prospects of getting rid of hypoxia with the nutrient reductions that have been agreed upon by the countries in the Baltic Sea basin and discuss the time scales of improvement in bottom water oxygen conditions.

  3. The Effects of Portulaca oleracea on Hypoxia-Induced Pulmonary Edema in Mice.

    Science.gov (United States)

    Yue, Tan; Xiaosa, Wen; Ruirui, Qi; Wencai, Shi; Hailiang, Xin; Min, Li

    2015-03-01

    Portulaca oleracea L. (PO) is known as "a vegetable for long life" due to its antioxidant, anti-inflammatory, and other pharmacological activities. However, the protective activity of the ethanol extract of PO (EEPO) against hypoxia-induced pulmonary edema has not been fully investigated. In this study, we exposed mice to a simulated altitude of 7000 meters for 0, 3, 6, 9, and 12 h to observe changes in the water content and transvascular leakage of the mouse lung. It was found that transvascular leakage increased to the maximum in the mouse lung after 6 h exposure to hypobaric hypoxia. Prophylactic administration of EEPO before hypoxic exposure markedly reduced the transvascular leakage and oxidative stress, and inhibited the upregulation of NF-kB in the mouse lung, as compared with the control group. In addition, EEPO significantly reduced the levels of proinflammatory cytokines and cell adhesion molecules in the lungs of mice, as compared with the hypoxia group. Our results show that EEPO can reduce initial transvascular leakage and pulmonary edema under hypobaric hypoxia conditions.

  4. Investigating the complexity of respiratory patterns during recovery from severe hypoxia

    Science.gov (United States)

    Akay, Metin; Sekine, Noriko

    2004-03-01

    Progressive hypoxemia in anesthetized, peripherally chemodenervated piglets results in initial depression of the phrenic neurogram (PN) culminating in phrenic silence and, eventually, gasping. These changes reverse after the 30 min reoxygenation (recovery) period. To determine if changes in the PN patterns correspond to changes in temporal patterning, we have used the approximate entropy (ApEn) method to examine the effects of maturation on the complexity of breathing patterns in chemodenervated, vagotomized and decerebrated piglets during severe hypoxia and reoxygenation. The phrenic neurogram in piglets was recorded during eupnea (normal breathing), severe hypoxia (gasping) and recovery from severe hypoxia in 31 piglets (2 35 days). Nonlinear dynamical analysis of the phrenic neurogram was performed using the ApEn method. The mean ApEn values for a recording of five consecutive breaths during eupnea, a few phrenic neurogram signals during gasping, the beginning of the recovery period, and five consecutive breaths at every 5 min interval for the 30 min recovery period were calculated. Our data suggest that gasping resulted in reduced duration of the phrenic neurogram, and the gasp-like patterns exist at the beginning of the recovery. But, the durations of phrenic neurograms during recovery were increased after 10 min postreoxygenation, but were restored 30 min post recovery. The ApEn (complexity) values of the phrenic neurogram during eupnea were higher than those of gasping and the early (the onset of) recovery from severe hypoxia (p < 0.01), but were not statistically different than 5 min post recovery regardless of the maturation stages. These results suggest that hypoxia results in a reversible reconfiguration of the central respiratory pattern generator.

  5. Inhibition of calcium uptake during hypoxia in developing zebrafish is mediated by hypoxia-inducible factor.

    Science.gov (United States)

    Kwong, Raymond W M; Kumai, Yusuke; Tzaneva, Velislava; Azzi, Estelle; Hochhold, Nina; Robertson, Cayleih; Pelster, Bernd; Perry, Steve F

    2016-12-15

    The present study investigated the potential role of hypoxia-inducible factor (HIF) in calcium homeostasis in developing zebrafish (Danio rerio). It was demonstrated that zebrafish raised in hypoxic water (30 mmHg; control, 155 mmHg P O 2 ) until 4 days post-fertilization exhibited a substantial reduction in whole-body Ca 2+ levels and Ca 2+ uptake. Ca 2+ uptake in hypoxia-treated fish did not return to pre-hypoxia (control) levels within 2 h of transfer back to normoxic water. Results from real-time PCR showed that hypoxia decreased the whole-body mRNA expression levels of the epithelial Ca 2+ channel (ecac), but not plasma membrane Ca 2+ -ATPase (pmca2) or Na + /Ca 2+ -exchanger (ncx1b). Whole-mount in situ hybridization revealed that the number of ecac-expressing ionocytes was reduced in fish raised in hypoxic water. These findings suggested that hypoxic treatment suppressed the expression of ecac, thereby reducing Ca 2+ influx. To further evaluate the potential mechanisms for the effects of hypoxia on Ca 2+ regulation, a functional gene knockdown approach was employed to prevent the expression of HIF-1αb during hypoxic treatment. Consistent with a role for HIF-1αb in regulating Ca 2+ balance during hypoxia, the results demonstrated that the reduction of Ca 2+ uptake associated with hypoxic exposure was not observed in fish experiencing HIF-1αb knockdown. Additionally, the effects of hypoxia on reducing the number of ecac-expressing ionocytes was less pronounced in HIF-1αb-deficient fish. Overall, the current study revealed that hypoxic exposure inhibited Ca 2+ uptake in developing zebrafish, probably owing to HIF-1αb-mediated suppression of ecac expression. © 2016. Published by The Company of Biologists Ltd.

  6. General Atomic reprocessing pilot plant: description and results of initial testing

    International Nuclear Information System (INIS)

    1977-12-01

    In June 1976 General Atomic completed the construction of a reprocessing head-end cold pilot plant. In the year since then, each system within the head end has been used for experiments which have qualified the designs. This report describes the equipment in the plant and summarizes the results of the initial phase of reprocessing testing

  7. Gravitational Waves from Known Pulsars: Results from the Initial Detector Era

    NARCIS (Netherlands)

    Aasi, J.; et al., [Unknown; Hessels, J.W.T.

    2014-01-01

    We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and

  8. Initial Laboratory-Scale Melter Test Results for Combined Fission Product Waste

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Brian J.; Crum, Jarrod V.; Buchmiller, William C.; Rieck, Bennett T.; Schweiger, Michael J.; Vienna, John D.

    2009-10-01

    This report describes the methods and results used to vitrify a baseline glass, CSLNTM-C-2.5 in support of the AFCI (Advanced Fuel Cycle Initiative) using a Quartz Crucible Scale Melter at the Pacific Northwest National Laboratory. Document number AFCI-WAST-PMO-MI-DV-2009-000184.

  9. Novel Field test design and initial result for AC and DC characterization for PV-panels

    DEFF Research Database (Denmark)

    Thorsteinsson, Sune; Riedel, Nicholas; Santamaria Lancia, Adrian Alejo

    This work describes the design and initial test results of a field test for PV modules, where the PV modules the majority of the time operates to produce power at their maximum power point. Sequentially the individual modules are switched into a measurement circuitry for IV curves and impedance s...

  10. The impact of hypoxia on oncolytic virotherapy

    Directory of Open Access Journals (Sweden)

    Guo ZS

    2011-11-01

    Full Text Available Z Sheng GuoUniversity of Pittsburgh Cancer Institute and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: The hypoxic tumor microenvironment plays significant roles in tumor cell metabolism and survival, tumor growth, and progression. Hypoxia modulates target genes in target cells mainly through an oxygen-sensing signaling pathway mediated by hypoxia-inducible factor of transcription factors. As a result, hypoxic tumor cells are resistant to conventional therapeutics such as radiation and chemotherapy. Oncolytic virotherapy may be a promising novel therapeutic for hypoxic cancer. Some oncolytic viruses are better adapted than others to the hypoxic tumor environment. Replication of adenoviruses from both groups B and C is inhibited, yet replication of herpes simplex virus is enhanced. Hypoxia seems to exert little or no effect on the replication of other oncolytic viruses. Vaccinia virus displayed increased cytotoxicity in some hypoxic cancer cells even though viral protein synthesis and transgene expression were not affected. Vesicular stomatitis virus replicated to similar levels in both hypoxic and normoxic conditions, and is effective for killing hypoxic cancer cells. However, vesicular stomatitis virus and reovirus, but not encephalomyocarditis virus, are sensitive to elevated levels of hypoxia-inducible factor-1α in renal cancer cells with the loss of von Hippel–Lindau tumor suppressor protein, because elevated hypoxia-inducible factor activity confers dramatically enhanced resistance to cytotoxicity mediated by vesicular stomatitis virus or reovirus. A variety of hypoxia-selective and tumor-type-specific oncolytic adenoviruses, generated by incorporating hypoxia-responsive elements into synthetic promoters to control essential genes for viral replication or therapeutic genes, have been shown to be safe and efficacious. Hypoxic tumor-homing macrophages can function effectively as carrier

  11. Reciprocating magnetic refrigerator for 2--4 K operation: Initial results

    International Nuclear Information System (INIS)

    Barclay, J.A.; Moze, O.; Paterson, L.

    1979-01-01

    The basic theory and design of a reciprocating magnetic refrigerator to pump heat from 2.2 to 4.2 K is presented. The results of initial experiments are shown. These results include conduction losses, eddy current losses, frictional losses, and mixing losses. Two cooling cycles were attempted and a net cooling power of 52 mW was observed at 1/60 Hz. The key problems in this design are identified and discussed

  12. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

    2014-02-26

    The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

  13. Acute physical exercise under hypoxia improves sleep, mood and reaction time.

    Science.gov (United States)

    de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

    2016-02-01

    This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time.

  14. Initial results from beam commissioning of the LHC beam dump system

    CERN Document Server

    Goddard, B; Carlier, E; Ducimetière, L; Gallet, E; Gyr, M; Jensen, L; Jones, R; Kain, V; Kramer, T; Lamont, M; Meddahi, M; Mertens, V; Risselada, Thys; Uythoven, J; Wenninger, J; Weterings, W

    2010-01-01

    Initial commissioning of the LHC beam dump system with beam took place in August and September 2008. The preparation, setting-up and the tests performed are described together with results of the extractions of beam into the dump lines. Analysis of the first detailed aperture measurements of the extraction channels and kicker performance derived from dilution sweep shapes are presented. The performance of the other equipment subsystems is summarised, in particular that of the dedicated dump system beam instrumentation.

  15. Initial results from NuSTAR observations of the Norma arm

    DEFF Research Database (Denmark)

    Bodaghee, Arash; Tomsick, John A.; Krivonos, Roman

    2014-01-01

    Results are presented for an initial survey of the Norma Arm gathered with the focusing hard X-ray telescope NuSTAR. The survey covers 0.2 deg2 of sky area in the 3-79 keV range with a minimum and maximum raw depth of 15 ks and 135 ks, respectively. Besides a bright black-hole X-ray binary...

  16. Initial results for electrochemical dissolution of spent EBR-II fuel

    International Nuclear Information System (INIS)

    Li, S. X.

    1998-01-01

    Initial results are reported for the anode behavior of spent metallic nuclear fuel in an electrorefining process. The anode behavior has been characterized in terms of the initial spent fuel composition and the final composition of the residual cladding hulls. A variety of results have been obtained depending on the experimental conditions. Some of the process variables considered are average and maximum cell voltage, average and maximum anode voltage, amount of electrical charge passed (coulombs or amp-hours) during the experiment, and cell resistance. The main goal of the experiments has been the nearly complete dissolution of uranium with the retention of zirconium and noble metal fission products in the cladding hulls. Analysis has shown that the most indicative parameters for determining an endpoint to the process, recognizing the stated goal, are the maximum anode voltage and the amount of electrical charge passed. For the initial experiments reported here, the best result obtained is greater than 98% uranium dissolution with approximately 50% zirconium retention. Noble metal fission product retention appears to be correlated with zirconium retention

  17. The amphibious fish Kryptolebias marmoratus uses different strategies to maintain oxygen delivery during aquatic hypoxia and air exposure.

    Science.gov (United States)

    Turko, Andy J; Robertson, Cayleih E; Bianchini, Kristin; Freeman, Megan; Wright, Patricia A

    2014-11-15

    Despite the abundance of oxygen in atmospheric air relative to water, the initial loss of respiratory surface area and accumulation of carbon dioxide in the blood of amphibious fishes during emersion may result in hypoxemia. Given that the ability to respond to low oxygen conditions predates the vertebrate invasion of land, we hypothesized that amphibious fishes maintain O2 uptake and transport while emersed by mounting a co-opted hypoxia response. We acclimated the amphibious fish Kryptolebias marmoratus, which are able to remain active for weeks in both air and water, for 7 days to normoxic brackish water (15‰, ~21kPa O2; control), aquatic hypoxia (~3.6kPa), normoxic air (~21 kPa) or aerial hypoxia (~13.6kPa). Angiogenesis in the skin and bucco-opercular chamber was pronounced in air- versus water-acclimated fish, but not in response to hypoxia. Aquatic hypoxia increased the O2-carrying capacity of blood via a large (40%) increase in red blood cell density and a small increase in the affinity of hemoglobin for O2 (P50 decreased 11%). In contrast, air exposure increased the hemoglobin O2 affinity (decreased P50) by 25% without affecting the number of red blood cells. Acclimation to aerial hypoxia both increased the O2-carrying capacity and decreased the hemoglobin O2 affinity. These results suggest that O2 transport is regulated both by O2 availability and also, independently, by air exposure. The ability of the hematological system to respond to air exposure independent of O2 availability may allow extant amphibious fishes, and may also have allowed primitive tetrapods to cope with the complex challenges of aerial respiration during the invasion of land. © 2014. Published by The Company of Biologists Ltd.

  18. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

    Directory of Open Access Journals (Sweden)

    Junie P Warrington

    Full Text Available Whole brain radiation therapy (WBRT is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia or 21% oxygen (normoxia for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

  19. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  20. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  1. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  2. Intermittent hypoxia increases insulin resistance in genetically obese mice.

    Science.gov (United States)

    Polotsky, Vsevolod Y; Li, Jianguo; Punjabi, Naresh M; Rubin, Arnon E; Smith, Philip L; Schwartz, Alan R; O'Donnell, Christopher P

    2003-10-01

    Obstructive sleep apnoea, a syndrome that leads to recurrent intermittent hypoxia, is associated with insulin resistance in obese individuals, but the mechanisms underlying this association remain unknown. We utilized a mouse model to examine the effects of intermittent hypoxia on insulin resistance in lean C57BL/6J mice and leptin-deficient obese (C57BL/6J-Lepob) mice. In lean mice, exposure to intermittent hypoxia for 5 days (short term) resulted in a decrease in fasting blood glucose levels (from 173 +/- 11 mg dl-1 on day 0 to 138 +/- 10 mg dl-1 on day 5, P obese mice, short-term intermittent hypoxia led to a decrease in blood glucose levels accompanied by a 607 +/- 136 % (P intermittent hypoxia was completely abolished by prior leptin infusion. Obese mice exposed to intermittent hypoxia for 12 weeks (long term) developed a time-dependent increase in fasting serum insulin levels (from 3.6 +/- 1.1 ng ml-1 at baseline to 9.8 +/- 1.8 ng ml-1 at week 12, P intermittent hypoxia is dependent on the disruption of leptin pathways.

  3. The expanding universe of hypoxia.

    Science.gov (United States)

    Zhang, Huafeng; Semenza, Gregg L

    2008-07-01

    Reduced oxygen availability (hypoxia) is sensed and transduced into changes in the activity or expression of cellular macromolecules. These responses impact on virtually all areas of biology and medicine. In this meeting report, we summarize major developments in the field that were presented at the 2008 Keystone Symposium on Cellular, Physiological, and Pathogenic Responses to Hypoxia.

  4. An Initiating-Event Analysis for PSA of Hanul Units 3 and 4: Results and Insights

    International Nuclear Information System (INIS)

    Kim, Dong-San; Park, Jin Hee

    2015-01-01

    As a part of the PSA, an initiating-event (IE) analysis was newly performed by considering the current state of knowledge and the requirements of the ASME/ANS probabilistic risk assessment (PRA) standard related to IE analysis. This paper describes the methods of, results and some insights from the IE analysis for the PSA of the Hanul units 3 and 4. In this study, as a part of the PSA for the Hanul units 3 and 4, an initiating-event (IE) analysis was newly performed by considering the current state of knowledge and the requirements of the ASME/ANS probabilistic risk assessment (PRA) standard. In comparison with the previous IE analysis, this study performed a more systematic and detailed analysis to identify potential initiating events, and calculated the IE frequencies by using the state-of-the-art methods and the latest data. As a result, not a few IE frequencies are quite different from the previous frequencies, which can change the major accident sequences obtained from the quantification of the PSA model

  5. Virtual enterprise architecture and methodology - Initial results from the Globeman21 project

    DEFF Research Database (Denmark)

    Vesterager, Johan; Larsen, Lars Bjørn; Gobbi, Chiara

    1999-01-01

    This paper will focus on presenting the initial results from the IMS project Globeman21 regarding generic models for Extended Enterprise Management (EEM). In particular the paper outlines a proposed architecture for the creation of virtual enterprises, industrial requirements regarding the generic...... models, terminology for describing extended enterprises, and initial considerations regarding a methodology for EEM. Globeman21 see the extended enterprise as a concept covering the totality of different concepts dealing with the expansion or extension of enterprise activities. One way of realising...... the concept of extended enterprise is through the creation of virtual enterprise, based on a more or less formalised network. This approach is the basis for the development of the generic EEM model within Globeman21....

  6. Leveraging finances for public health system improvement: results from the Turning Point initiative.

    Science.gov (United States)

    Bekemeier, Betty; Riley, Catharine M; Berkowitz, Bobbie

    2007-01-01

    Reforming the public health infrastructure requires substantial system changes at the state level; state health agencies, however, often lack the resources and support for strategic planning and systemwide improvement. The Turning Point Initiative provided support for states to focus on large-scale system changes that resulted in increased funding for public health capacity and infrastructure development. Turning Point provides a test case for obtaining financial and institutional resources focused on systems change and infrastructure development-areas for which it has been historically difficult to obtain long-term support. The purpose of this exploratory, descriptive survey research was to enumerate the actual resources leveraged toward public health system improvement through the partnerships, planning, and implementation activities funded by the Robert Wood Johnson Foundation as a part of the Turning Point Initiative.

  7. Hypoxia as a biomarker for radioresistant cancer stem cells.

    Science.gov (United States)

    Peitzsch, Claudia; Perrin, Rosalind; Hill, Richard P; Dubrovska, Anna; Kurth, Ina

    2014-08-01

    Tumor initiation, growth and relapse after therapy are thought to be driven by a population of cells with stem cell characteristics, named cancer stem cells (CSC). The regulation of their radiation resistance and their maintenance is poorly understood. CSC are believed to reside preferentially in special microenvironmental niches located within tumor tissues. The features of these niches are of crucial importance for CSC self-renewal, metastatic potential and therapy resistance. One of the characteristics of solid tumors is occurrence of less oxygenated (hypoxic regions), which are believed to serve as so-called hypoxic niches for CSC. The purpose of this review was the critical discussion of the supportive role of hypoxia and hypoxia-related pathways during cancer progression and radiotherapy resistance and the relevance for therapeutic implications in the clinic. It is generally known since decades that hypoxia inside solid tumors impedes chemo- and radiotherapy. However, there is limited evidence to date that targeting hypoxic regions during conventional therapy is effective. Nonetheless improved hypoxia-imaging technologies and image guided individualized hypoxia targeted therapy in conjunction with the development of novel molecular targets may be able to challenge the protective effect on the tumor provided by hypoxia.

  8. Salinity-induced stratification and the onset of hypoxia during the Holocene Thermal Maximum and the Medieval Climate Anomaly

    Science.gov (United States)

    Papadomanolaki, Nina; Dijkstra, Nikki; van Helmond, Niels; Sangiorgi, Francesca; Hagens, Mathilde; Kotthoff, Ulrich; Slomp, Caroline

    2016-04-01

    During the past ~8000 years the Baltic Sea has experienced three distinct intervals of hypoxia, of which the last one is still ongoing. These intervals are characterized by enhanced sedimentary organic matter burial and enrichment of redox-sensitive metals, such as molybdenum and iron. The first two of these intervals occurred during the Holocene Thermal Maximum (HTM) and the Medieval Climate Anomaly (MCA), two phases with high temperatures and changed precipitation patterns. Studies focussing on the Holocene sedimentary record of the Baltic Sea aim at clarifying the causes of the initiation, evolution and termination of these hypoxic intervals, as well as their consequences. This information could help to potentially aid in finding solutions for the mitigation of present-day hypoxia in the Baltic Sea. The factors contributing to hypoxia development during the HTM and MCA are still debated. Here we present data from a core retrieved during Integrated Ocean Drilling Program (IODP) Expedition 347 in the Landsort Deep basin, the deepest basin of the Baltic Sea at 463m water depth. Sediments were analysed at a high resolution using inorganic geochemical and (mainly marine) palynological proxies. Dinoflagellate cyst (dinocyst) assemblages and total elemental compositions provide clues on the role of salinity in enhancing stratification, ultimately causing hypoxia. During the onset of the HTM changes in salinity, as indicated by the palynology, closely follow changes in sedimentary organic carbon burial and trace metal concentrations. This suggests that stratification was an important cause of hypoxia during the HTM. In contrast, the palynology suggests that reduced stratification did not contribute to re-oxygenation during the termination of the HTM. We did not observe major changes in the palynology throughout the hypoxic interval of the MCA. Our results thus suggest that changes in salinity did not cause the onset and termination of hypoxia during the MCA.

  9. Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Mahendran Botlagunta

    2011-03-01

    Full Text Available DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region.

  10. The radiation response of cells recovering after chronic hypoxia

    International Nuclear Information System (INIS)

    Kwok, T.T.; Sutherland, R.M.

    1989-01-01

    Experiments were performed to study the influence of hypoxic pretreatment on the radiation response of A431 human squamous carcinoma cells. Reaeration for 10 min after chronic hypoxia (greater than 2 h) was found to enhance the radiosensitivity of A431 cells, and the maximal effect was seen for those cells reaerated after 12 h of hypoxia. The radiosensitivity enhancement for reaerated cells after 12 h of hypoxia was maximized by 5 min after the return to aerobic conditions and reached the control level by 12 h of reaeration. This enhanced radiosensitive state was characterized by a reduced shoulder region and increased slope of the radiation dose-response curve for cells in both the exponential and plateau phases of growth. There was a slight increase in the number of G1 and decrease in the number of S and G2 + M cells for both exponential- and plateau-phase cultures following 12 h hypoxic treatment. Although growth inhibition induced by 12 h of hypoxia was seen for cells in the exponential phase, there was no cell number change in the plateau-phase culture after hypoxia. Plating efficiency (PE) of cells in both growth phases was reduced by 30% after hypoxia. Furthermore, in the exponential-phase culture, the extent of reduction in PE after hypoxia was similar among cells in different phases of the cell cycle. Although S-phase cells in exponentially growing cultures were relatively more resistant to radiation than G1 and G2 + M cells, the cell age-response pattern was the same whether the cells had been aerobic or hypoxic before reaeration and irradiation. Furthermore, the enhancement ratio associated with reaeration after 12 h of hypoxia for these three subpopulations of cells was 1.3. Our results indicate that the increase in radiosensitivity due to reaeration after chronic hypoxia is unlikely to be related to the changes of cell cycle stage and growth phase during hypoxic treatment

  11. Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results.

    Science.gov (United States)

    Richardson, R R; Siqueira, E B; Cerullo, L J

    1979-09-01

    Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.

  12. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

    Directory of Open Access Journals (Sweden)

    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  13. Initial Results from the Lost Alpha Diagnostics on Joint European Torus

    Energy Technology Data Exchange (ETDEWEB)

    Darrow, Doug; Cecil, Ed; Ellis, Bob; Fullard, Keith; Hill, Ken; Horton, Alan; Kiptily, Vasily; Pedrick, Les; Reich, Matthias

    2007-07-25

    Two devices have been installed in the Joint European Torus (JET) vacuum vessel near the plasma boundary to investigate the loss of energetic ions and fusion products in general and alpha particles in particular during the upcoming JET experiments. These devices are (i) a set of multichannel thin foil Faraday collectors, and (ii) a well collimated scintillator which is optically connected to a charge-coupled device. Initial results, including the radial energy and poloidal dependence of lost ions from hydrogen and deuterium plasmas during the 2005–06 JET restart campaign, will be presented.

  14. Neonatal screening for four lysosomal storage diseases with a digital microfluidics platform: Initial results in Brazil

    Directory of Open Access Journals (Sweden)

    Eurico Camargo Neto

    2018-06-01

    Full Text Available Abstract We describe the initial results of a neonatal screening program for four lysosomal storage diseases (MPS I, Pompe, Gaucher and Fabry using the digital microfluidics methodology. The method successfully identified patients previously diagnosed with these diseases and was used to test dried blood spot samples obtained from 10,527 newborns aged 2 to 14 days. The digital microfluidic technology shows potential for a simple, rapid and high-throughput screening for these four diseases in a standard neonatal screening laboratory.

  15. Initial Results from the Lost Alpha Diagnostics on Joint European Torus

    International Nuclear Information System (INIS)

    Darrow, Doug; Baeumel, Stefan; Cecil, Ed; Ellis, Bob; Fullard, Keith; Hill, Ken; Horton, Alan; Kiptily, Vasily; Pedrick, Les; Reich, Matthias; Werner, Andreas

    2007-01-01

    Two devices have been installed in the Joint European Torus (JET) vacuum vessel near the plasma boundary to investigate the loss of energetic ions and fusion products in general and alpha particles in particular during the upcoming JET experiments. These devices are (i) a set of multichannel thin foil Faraday collectors, and (ii) a well collimated scintillator which is optically connected to a charge-coupled device. Initial results, including the radial energy and poloidal dependence of lost ions from hydrogen and deuterium plasmas during the 2005-06 JET restart campaign, will be presented.

  16. Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression.

    Science.gov (United States)

    Hassan, Atiq; Arnold, Breanna M; Caine, Sally; Toosi, Behzad M; Verge, Valerie M K; Muir, Gillian D

    2018-01-01

    One of the most promising approaches to improve recovery after spinal cord injury (SCI) is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH, brief exposures to reduced O2 levels alternating with normal O2 levels) initiates plasticity in respiratory systems and has been shown to improve recovery in respiratory and non-respiratory spinal systems after SCI in experimental animals and humans. Although the mechanism by which AIH elicits its effects after SCI are not well understood, AIH is known to alter protein expression in spinal neurons in uninjured animals. Here, we examine hypoxia- and plasticity-related protein expression using immunofluorescence in spinal neurons in SCI rats that were treated with AIH combined with motor training, a protocol which has been demonstrated to improve recovery of forelimb function in this lesion model. Specifically, we assessed protein expression in spinal neurons from animals with incomplete cervical SCI which were exposed to AIH treatment + motor training either for 1 or 7 days. AIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 weeks post-SCI. Both 1 or 7 days of AIH treatment + motor training resulted in significantly increased expression of the transcription factor hypoxia-inducible factor-1α (HIF-1α) relative to normoxia-treated controls, in neurons both proximal (cervical) and remote (lumbar) to the SCI. All other markers examined were significantly elevated in the 7 day AIH + motor training group only, at both cervical and lumbar levels. These markers included vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and phosphorylated and nonphosphorylated forms of the BDNF receptor tropomyosin-related kinase B (TrkB). In summary, AIH induces plasticity at the cellular level after SCI by altering the expression of major plasticity- and hypoxia-related proteins at spinal regions

  17. [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bekaert, Lien [CHU de Caen, Department of Neurology, Caen (France); Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); CHU de Caen, Department of Neurosurgery, Caen (France); CHU de Caen, Service de Neurochirurgie, Caen (France); Valable, Samuel; Collet, Solene; Bordji, Karim; Petit, Edwige; Bernaudin, Myriam [Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); Lechapt-Zalcman, Emmanuele [Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); CHU de Caen, Department of Pathology, Caen (France); Ponte, Keven [CHU de Caen, Department of Neurosurgery, Caen (France); Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); Constans, Jean-Marc [Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); CHU de Caen, Department of Neuroradiology, Caen (France); Levallet, Guenaelle [CHU de Caen, Department of Pathology, Caen (France); Branger, Pierre [CHU de Caen, Department of Neurology, Caen (France); Emery, Evelyne [CHU de Caen, Department of Neurosurgery, Caen (France); Manrique, Alain [CHU de Caen, Department of Nuclear Medicine, Caen (France); Barre, Louisa [Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/LDM-TEP group, Caen (France); Guillamo, Jean-Sebastien [CHU de Caen, Department of Neurology, Caen (France); Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen (France); CHU de Nimes, Department of Neurology, Nimes (France)

    2017-08-15

    Hypoxia in gliomas is associated with tumor resistance to radio- and chemotherapy. However, positron emission tomography (PET) imaging of hypoxia remains challenging, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival. In this prospective single center clinical study, 33 glioma patients (grade IV: n = 24, III: n = 3, and II: n = 6) underwent [18F]-FMISO PET and MRI including relative cerebral blood volume (rCBV) maps before surgery. Maximum standardized uptake values (SUVmax) and hypoxic volume were calculated, defining two groups of patients based on the presence or absence of [18F]-FMISO uptake. After surgery, molecular quantification of CAIX, VEGF, Ang2 (rt-qPCR), and HIF-1α (immunohistochemistry) were performed on tumor specimens. [18F]-FMISO PET uptake was closely linked to tumor grade, with high uptake in glioblastomas (GB, grade IV). Expression of biomarkers of hypoxia (CAIX, HIF-1α), and angiogenesis markers (VEGF, Ang2, rCBV) were significantly higher in the [18F]-FMISO uptake group. We found correlations between the degree of hypoxia (hypoxic volume and SUVmax) and expression of HIF-1α, CAIX, VEGF, Ang2, and rCBV (p < 0.01). Patients without [18F]-FMISO uptake had a longer survival time than uptake positive patients (log-rank, p < 0.005). Tumor hypoxia as evaluated by [18F]-FMISO PET is associated with the expression of hypoxia markers on a molecular level and is related to angiogenesis. [18F]-FMISO uptake is a mark of an aggressive tumor, almost always a glioblastoma. Our results underline that [18F]-FMISO PET could be useful to guide glioma treatment, and in particular radiotherapy, since hypoxia is a well-known factor of resistance. (orig.)

  18. Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

    Energy Technology Data Exchange (ETDEWEB)

    Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

    2003-12-01

    Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

  19. Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor.

    Science.gov (United States)

    Tarhonskaya, Hanna; Hardy, Adam P; Howe, Emily A; Loik, Nikita D; Kramer, Holger B; McCullagh, James S O; Schofield, Christopher J; Flashman, Emily

    2015-08-07

    The hypoxia-inducible factor (HIF) hydroxylases regulate hypoxia sensing in animals. In humans, they comprise three prolyl hydroxylases (PHD1-3 or EGLN1-3) and factor inhibiting HIF (FIH). FIH is an asparaginyl hydroxylase catalyzing post-translational modification of HIF-α, resulting in reduction of HIF-mediated transcription. Like the PHDs, FIH is proposed to have a hypoxia-sensing role in cells, enabling responses to changes in cellular O2 availability. PHD2, the most important human PHD isoform, is proposed to be biochemically/kinetically suited as a hypoxia sensor due to its relatively high sensitivity to changes in O2 concentration and slow reaction with O2. To ascertain whether these parameters are conserved among the HIF hydroxylases, we compared the reactions of FIH and PHD2 with O2. Consistent with previous reports, we found lower Km(app)(O2) values for FIH than for PHD2 with all HIF-derived substrates. Under pre-steady-state conditions, the O2-initiated FIH reaction is significantly faster than that of PHD2. We then investigated the kinetics with respect to O2 of the FIH reaction with ankyrin repeat domain (ARD) substrates. FIH has lower Km(app)(O2) values for the tested ARDs than HIF-α substrates, and pre-steady-state O2-initiated reactions were faster with ARDs than with HIF-α substrates. The results correlate with cellular studies showing that FIH is active at lower O2 concentrations than the PHDs and suggest that competition between HIF-α and ARDs for FIH is likely to be biologically relevant, particularly in hypoxic conditions. The overall results are consistent with the proposal that the kinetic properties of individual oxygenases reflect their biological capacity to act as hypoxia sensors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Hypoxia determines survival outcomes of bacterial infection through HIF-1α-dependent reprogramming of leukocyte metabolism

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J.P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Coelho, P.D.S.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N.M.

    2017-01-01

    Hypoxia and bacterial infection frequently coexist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both Staphylococcus aureus and Streptococcus pneumoniae infections rapidly induced progressive neutrophil-mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning ...

  1. Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

    NARCIS (Netherlands)

    Stegeman, H.; Span, P.N.; Peeters, W.J.M.; Verheijen, M.M.; Grenman, R.; Meijer, T.W.H.; Kaanders, J.H.A.M.; Bussink, J.

    2016-01-01

    BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by

  2. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    Science.gov (United States)

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

  3. Compact Multipurpose Mobile Laser Scanning System — Initial Tests and Results

    Directory of Open Access Journals (Sweden)

    Craig Glennie

    2013-01-01

    Full Text Available We describe a prototype compact mobile laser scanning system that may be operated from a backpack or unmanned aerial vehicle. The system is small, self-contained, relatively inexpensive, and easy to deploy. A description of system components is presented, along with the initial calibration of the multi-sensor platform. The first field tests of the system, both in backpack mode and mounted on a helium balloon for real-world applications are presented. For both field tests, the acquired kinematic LiDAR data are compared with highly accurate static terrestrial laser scanning point clouds. These initial results show that the vertical accuracy of the point cloud for the prototype system is approximately 4 cm (1σ in balloon mode, and 3 cm (1σ in backpack mode while horizontal accuracy was approximately 17 cm (1σ for the balloon tests. Results from selected study areas on the Sacramento River Delta and San Andreas Fault in California demonstrate system performance, deployment agility and flexibility, and potential for operational production of high density and highly accurate point cloud data. Cost and production rate trade-offs place this system in the niche between existing airborne and tripod mounted LiDAR systems.

  4. Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype

    Directory of Open Access Journals (Sweden)

    Robinson Claire M

    2012-08-01

    Full Text Available Abstract Background Pulmonary fibrosis is a debilitating and lethal disease with no effective treatment options. Understanding the pathological processes at play will direct the application of novel therapeutic avenues. Hypoxia has been implicated in the pathogenesis of pulmonary fibrosis yet the precise mechanism by which it contributes to disease progression remains to be fully elucidated. It has been shown that chronic hypoxia can alter DNA methylation patterns in tumour-derived cell lines. This epigenetic alteration can induce changes in cellular phenotype with promoter methylation being associated with gene silencing. Of particular relevance to idiopathic pulmonary fibrosis (IPF is the observation that Thy-1 promoter methylation is associated with a myofibroblast phenotype where loss of Thy-1 occurs alongside increased alpha smooth muscle actin (α-SMA expression. The initial aim of this study was to determine whether hypoxia regulates DNA methylation in normal human lung fibroblasts (CCD19Lu. As it has been reported that hypoxia suppresses Thy-1 expression during lung development we also studied the effect of hypoxia on Thy-1 promoter methylation and gene expression. Methods CCD19Lu were grown for up to 8 days in hypoxia and assessed for global changes in DNA methylation using flow cytometry. Real-time PCR was used to quantify expression of Thy-1, α-SMA, collagen I and III. Genomic DNA was bisulphite treated and methylation specific PCR (MSPCR was used to examine the methylation status of the Thy-1 promoter. Results Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2′-deoxycytidine. MSPCR revealed that Thy-1 became methylated following fibroblast exposure to 1% O2. Conclusion These data suggest that global and

  5. A preclinical model for noninvasive imaging of hypoxia-induced gene expression; comparison with an exogenous marker of tumor hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Wen Bixiu; Burgman, Paul; Zanzonico, Pat; O' Donoghue, Joseph; Li, Gloria C.; Ling, C. Clifton [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York (United States); Cai Shangde; Finn, Ron [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York (United States); Serganova, Inna [Memorial Sloan-Kettering Cancer Center, Department of Neurology, New York (United States); Blasberg, Ronald; Gelovani, Juri [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York (United States); Memorial Sloan-Kettering Cancer Center, Department of Neurology, New York (United States)

    2004-11-01

    Hypoxia is associated with tumor aggressiveness and is an important cause of resistance to radiation therapy and chemotherapy. Assays of tumor hypoxia could provide selection tools for hypoxia-modifying treatments. The purpose of this study was to develop and characterize a rodent tumor model with a reporter gene construct that would be transactivated by the hypoxia-inducible molecular switch, i.e., the upregulation of HIF-1. The reporter gene construct is the herpes simplex virus 1-thymidine kinase (HSV1-tk) fused with the enhanced green fluorescent protein (eGFP) under the regulation of an artificial hypoxia-responsive enhancer/promoter. In this model, tumor hypoxia would up-regulate HIF-1, and through the hypoxia-responsive promoter transactivate the HSV1-tkeGFPfusion gene. The expression of this reporter gene can be assessed with the {sup 124}I-labeled reporter substrate 2'-fluoro-2'-deoxy-1-{beta}-d-arabinofuranosyl-5-iodouracil ({sup 124}I-FIAU), which is phosphorylated by the HSV1-tk enzyme and trapped in the hypoxic cells. Animal positron emission tomography (microPET) and phosphor plate imaging (PPI) were used in this study to visualize the trapped {sup 124}I-FIAU, providing a distribution of the hypoxia-induced molecular events. The distribution of {sup 124}I-FIAU was also compared with that of an exogenous hypoxic cell marker, {sup 18}F-fluoromisonidazole (FMISO). Our results showed that {sup 124}I-FIAU microPET imaging of the hypoxia-induced reporter gene expression is feasible, and that the intratumoral distributions of {sup 124}I-FIAU and {sup 18}F-FMISO are similar. In tumor sections, detailed radioactivity distributions were obtained with PPI which also showed similarity between {sup 124}I-FIAU and {sup 18}F-FMISO. This reporter system is sufficiently sensitive to detect hypoxia-induced transcriptional activation by noninvasive imaging and might provide a valuable tool in studying tumor hypoxia and in validating existing and future

  6. Turbulence modeling with fractional derivatives: Derivation from first principles and initial results

    Science.gov (United States)

    Epps, Brenden; Cushman-Roisin, Benoit

    2017-11-01

    Fluid turbulence is an outstanding unsolved problem in classical physics, despite 120+ years of sustained effort. Given this history, we assert that a new mathematical framework is needed to make a transformative breakthrough. This talk offers one such framework, based upon kinetic theory tied to the statistics of turbulent transport. Starting from the Boltzmann equation and ``Lévy α-stable distributions'', we derive a turbulence model that expresses the turbulent stresses in the form of a fractional derivative, where the fractional order is tied to the transport behavior of the flow. Initial results are presented herein, for the cases of Couette-Poiseuille flow and 2D boundary layers. Among other results, our model is able to reproduce the logarithmic Law of the Wall in shear turbulence.

  7. Results of the initial test program for the Sandia Pulsed Reactor III (SPR III)

    International Nuclear Information System (INIS)

    Estes, B.F.; Reuscher, J.A.

    1976-08-01

    This document presents a detailed discussion of the reactor including the mechanical and nuclear design characteristics. Also presented are the complete results of the Initial Approach to Critical and the Zero-and-Low Power testing programs. Reactivity worth measurements are given for such parameters as control element integral worth, Safety Block integral worth, and various materials (polyethylene, copper, lead, etc) as a function of position relative to the core. Subcritical reactivity measurements made during the approach to critical generally proved to be in reasonably good agreement with design values due to the good source-fuel-detector geometry possible with a reactor of this type. Subsequent dynamic measurements for reactivity worths are shown to be in good agreement with calculated results

  8. Results of initial analyses of the salt (macro) batch 11 Tank 21H qualification samples

    Energy Technology Data Exchange (ETDEWEB)

    Peters, T. B. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-10-23

    Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Interim Salt Disposition Project (ISDP) Salt (Macro) Batch 11 for processing through the Actinide Removal Process (ARP) and the Modular Caustic-Side Solvent Extraction Unit (MCU). This document reports the initial results of the analyses of samples of Tank 21H. Analysis of the Tank 21H Salt (Macro) Batch 11 composite sample indicates that the material does not display any unusual characteristics or observations, such as floating solids, the presence of large amounts of solids, or unusual colors. Further sample results will be reported in a future document. This memo satisfies part of Deliverable 3 of the Technical Task Request (TTR).

  9. Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

    Directory of Open Access Journals (Sweden)

    Joseph C Sanchez

    2017-10-01

    Full Text Available A form of dwarfism known as Meier-Gorlin syndrome (MGS is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5. These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45. The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C. We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

  10. Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

    Science.gov (United States)

    Sanchez, Joseph C; Kwan, Elizabeth X; Pohl, Thomas J; Amemiya, Haley M; Raghuraman, M K; Brewer, Bonita J

    2017-10-01

    A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

  11. Hypoxia positron emission tomography imaging: combining information on perfusion and tracer retention to improve hypoxia specificity

    DEFF Research Database (Denmark)

    Busk, Morten; Munk, Ole L; Jakobsen, Steen S

    2017-01-01

    BACKGROUND: Static positron emission tomography (PET) allows mapping of tumor hypoxia, but low resolution and slow tracer retention/clearance results in poor image contrast and the risk of missing areas where hypoxic cells and necrosis are intermixed. Fully dynamic PET may improve accuracy but scan...

  12. Implementation of STUD Pulses at the Trident Laser and Initial Results

    Science.gov (United States)

    Johnson, R. P.; Shimada, T.; Montgomery, D. S.; Afeyan, B.; Hüller, S.

    2012-10-01

    Controlling and mitigating laser-plasma instabilities such as stimulated Brillouin scattering, stimulated Raman scattering, and crossed-beam energy transfer is important to achieve high-gain inertial fusion using laser drivers. Recent theory and simulations show that these instabilities can be largely controlled using laser pulses consisting of spike trains of uneven duration and delay (STUD) by modulating the laser on a picosecond time scale [1,2]. We have designed and implemented a STUD pulse generator at the LANL Trident Laser Facility using Fourier synthesis to produce a 0.5-ns envelope of psec-duration STUD pulses using a spatial light modulator. Initial results from laser propagation tests and measurements as well as initial laser-plasma characterization experiments will be presented.[4pt] [1] B. Afeyan and S. H"uller, ``Optimal Control of Laser Plasma Instabilities using STUD pulses,'' IFSA 2011, P.Mo.1, to appear in Euro. Phys. J. Web of Conf. (2012).[2] S. H"uller and B. Afeyan, ``Simulations of drastically reduced SBS with STUD pulses,'' IFSA 2011, O.Tu8-1, to appear in Euro. Phys. J. Web of Conf. (2012).

  13. Results from the Data & Democracy initiative to enhance community-based organization data and research capacity.

    Science.gov (United States)

    Carroll-Scott, Amy; Toy, Peggy; Wyn, Roberta; Zane, Jazmin I; Wallace, Steven P

    2012-07-01

    In an era of community-based participatory research and increased expectations for evidence-based practice, we evaluated an initiative designed to increase community-based organizations' data and research capacity through a 3-day train-the-trainer course on community health assessments. We employed a mixed method pre-post course evaluation design. Various data sources collected from 171 participants captured individual and organizational characteristics and pre-post course self-efficacy on 19 core skills, as well as behavior change 1 year later among a subsample of participants. Before the course, participants reported limited previous experience with data and low self-efficacy in basic research skills. Immediately after the course, participants demonstrated statistically significant increases in data and research self-efficacy. The subsample reported application of community assessment skills to their work and increased use of data 1 year later. Results suggest that an intensive, short-term training program can achieve large immediate gains in data and research self-efficacy in community-based organization staff. In addition, they demonstrate initial evidence of longer-term behavior change related to use of data and research skills to support their community work.

  14. Initial clinical results of linac-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Shrieve, Dennis C.; Alexander, Eben; Kaiser, Ursula B.; Richardson, Gary E.; Black, Peter McL.; Loeffler, Jay S.

    1998-01-01

    Purpose: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment. Subjects and Methods: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm 3 for SRS and 5.7 cm 3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses. Results: Disease control--The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects--The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly

  15. Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Dai Yao; Bae, Kyungmi; Siemann, Dietmar W.

    2011-01-01

    Purpose: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. Methods and Materials: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. 'Wound-healing' and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. Results: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. Conclusions: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.

  16. Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia.

    Science.gov (United States)

    Santos, S A; Silva, E T; Caris, A V; Lira, F S; Tufik, S; Dos Santos, R V T

    2016-08-01

    Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P exercise (P exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P exercise in hypoxia without supplementation (P exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise. © 2016 The British Dietetic Association Ltd.

  17. Initial test results of an ionization chamber shower detector for a LHC luminosity monitor

    International Nuclear Information System (INIS)

    Datte, P.; Beche, J.-F.; Haguenauer, M.; Manfredi, P.F.; Manghisoni, M.; Millaud, J.; Placidi, M.; Ratti, L.; Riot, V.; Schmickler, H.; Speziali, V.; Turner, W.

    2002-01-01

    A novel, segmented, multi-gap, pressurized gas ionization chamber is being developed for optimization of the luminosity of the LHC. The ionization chambers are to be installed in the front quadrupole and zero degree neutral particle absorbers in the high luminosity IRs and sample the energy deposited near the maxima of the hadronic/electromagnetic showers in these absorbers. The ionization chambers are instrumented with low noise, fast, pulse shaping electronics to be capable of resolving individual bunch crossings at 40 MHz. In this paper we report the initial results of our second test of this instrumentation in an SPS external proton beam. Single 300 GeV protons are used to simulate the hadronic/electromagnetic shower produced by the forward collision products from the interaction regions of the LHC. The capability of instrumentations to measure the luminosity of individual bunches in a 40 MHz bunch train is demonstrated

  18. Initial results from the ISEE-1 and -2 plasma wave investigation

    International Nuclear Information System (INIS)

    Gurnett, D.A.; Anderson, R.R.; Smith, E.J.

    1979-01-01

    In this paper the authors present an initial survey of results from the plasma wave experiments on the ISEE-1 and -2 spacecraft which are in nearly identical orbits passing through the Earth's magneotsphere at radial distances out to about 22.5 Rsub(e). Essentially every crossing of the Earth's bow shock can be associated with an intense burst of electrostatic and whistler-mode turbulence at the shock, with substanial wave intensities in both the upstream and downstream regions. In the magnetosphere high resolution spectrograms of the electric field show an extremely complex distribution of plasma and radio emission, with numerous resonance and cutoff effects. High resolution spectrograms of kilometric radio emissions are also presented which show an extremely complex frequency-time structure with many closely spaced narrow-band emissions. (Auth.)

  19. Initial cathode processing experiences and results for the treatment of spent fuel

    International Nuclear Information System (INIS)

    Westphal, B.R.; Laug, D.V.; Brunsvold, A.R.; Roach, P.D.

    1996-01-01

    As part of the spent fuel treatment demonstration at Argonne National Laboratory, a vacuum distillation process is being employed for the recovery of uranium following an electrorefining process. Distillation of a salt electrolyte, primarily consisting of a eutectic mixture of lithium and potassium chlorides, from uranium is achieved by a batch operation termed ''cathode processing.'' Cathode processing is performed in a retort furnace which enables the production of a stable uranium product that can be isotopically diluted and stored. To date, experiments have been performed with two distillation units; one for prototypical testing and the other for actual spent fuel treatment operations. The results and experiences from these initial experiments with both units will be discussed as well as problems encountered and their resolution

  20. Initial results from an agressive roentgenological and surgical approach to acute mesenteric ischemia.

    Science.gov (United States)

    Boley, S J; Sprayregan, S; Siegelman, S S; Veith, F J

    1977-12-01

    The 70% to 80% mortality rate of patients with acute mesenteric ischemia (AMI) has remained unchanged over the past 40 years. We report here the initial results using an aggressive approach to this problem. This included the earlier and more liberal use of angiography in patients at risk and the intra-arterial infusion of papaverine for the relief of superior mesenteric artery (SMA) vasoconstriction in both nonocclusive and occlusive forms of AMI. Of the first 50 patients managed by this approach, 35 (70%) had AMI demonstrated by SMA angiography, Nineteen (54%) of these 35 patients survived, including nine of 15 patients with nonocclusive mesenteric ischemia, seven of 16 with SMA embolus, two of three patients with SMA thrombosis, and the one patient with mesenteric venous thrombosis. Seventeen of the 19 survivors lost no bowel or had excision of less than 3 feet of small intestine.

  1. Initial results of the high resolution edge Thomson scattering upgrade at DIII-D.

    Science.gov (United States)

    Eldon, D; Bray, B D; Deterly, T M; Liu, C; Watkins, M; Groebner, R J; Leonard, A W; Osborne, T H; Snyder, P B; Boivin, R L; Tynan, G R

    2012-10-01

    Validation of models of pedestal structure is an important part of predicting pedestal height and performance in future tokamaks. The Thomson scattering diagnostic at DIII-D has been upgraded in support of validating these models. Spatial and temporal resolution, as well as signal to noise ratio, have all been specifically enhanced in the pedestal region. This region is now diagnosed by 20 view-chords with a spacing of 6 mm and a scattering length of just under 5 mm sampled at a nominal rate of 250 Hz. When mapped to the outboard midplane, this corresponds to ~3 mm spacing. These measurements are being used to test critical gradient models, in which pedestal gradients increase in time until a threshold is reached. This paper will describe the specifications of the upgrade and present initial results of the system.

  2. Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment

    International Nuclear Information System (INIS)

    Álvarez, V; Cárcel, S; Cervera, A; Díaz, J; Ferrario, P; Gil, A; Borges, F I G; Conde, C A N; Dias, T H V T; Fernandes, L M P; Freitas, E D C; Castel, J; Cebrián, S; Dafni, T; Egorov, M; Gehman, V M; Goldschmidt, A; Esteve, R; Evtoukhovitch, P; Ferreira, A L

    2013-01-01

    NEXT-DEMO is a large-scale prototype of the NEXT-100 detector, an electroluminescent time projection chamber that will search for the neutrinoless double beta decay of XE using 100–150 kg of enriched xenon gas. NEXT-DEMO was built to prove the expected performance of NEXT-100, namely, energy resolution better than 1% FWHM at 2.5 MeV and event topological reconstruction. In this paper we describe the prototype and its initial results. A resolution of 1.75% FWHM at 511 keV (which extrapolates to 0.8% FWHM at 2.5 MeV) was obtained at 10 bar pressure using a gamma-ray calibration source. Also, a basic study of the event topology along the longitudinal coordinate is presented, proving that it is possible to identify the distinct dE/dx of electron tracks in high-pressure xenon using an electroluminescence TPC.

  3. Initial tank calibration at NUCEF critical facility. 1. Measurement procedure and its result

    International Nuclear Information System (INIS)

    Yanagisawa, Hiroshi; Mineo, Hideaki; Tonoike, Kotaro; Takeshita, Isao; Hoshi, Katsuya; Hagiwara, Hiroyuki.

    1994-07-01

    Initial tank calibrations were carried out prior to hot operation of critical facilities in NUCEF: Nuclear Fuel Cycle Safety Engineering Research Facility, for the purpose of the nuclear material accountancy and control for the facility. Raw calibration data were collected from single run per one tank by measuring differential pressure with dip-tube systems, weight of calibration liquid (demineralized water) poured into the tank, temperature in the tank and so on, without operation of tank ventilation system. Volume and level data were obtained by applying density and buoyancy corrections to the raw data. As a result, the evaluated measurement errors of volume and level were small enough, e.g. within 0.2 lit. and 1.0 mm, respectively, for Pu accountancy tanks. This paper summarizes the above-mentioned measurement procedures, collected data, data correction procedures and evaluated measurement errors. (author)

  4. Sensitivity Analysis of FEAST-Metal Fuel Performance Code: Initial Results

    International Nuclear Information System (INIS)

    Edelmann, Paul Guy; Williams, Brian J.; Unal, Cetin; Yacout, Abdellatif

    2012-01-01

    This memo documents the completion of the LANL milestone, M3FT-12LA0202041, describing methodologies and initial results using FEAST-Metal. The FEAST-Metal code calculations for this work are being conducted at LANL in support of on-going activities related to sensitivity analysis of fuel performance codes. The objective is to identify important macroscopic parameters of interest to modeling and simulation of metallic fuel performance. This report summarizes our preliminary results for the sensitivity analysis using 6 calibration datasets for metallic fuel developed at ANL for EBR-II experiments. Sensitivity ranking methodology was deployed to narrow down the selected parameters for the current study. There are approximately 84 calibration parameters in the FEAST-Metal code, of which 32 were ultimately used in Phase II of this study. Preliminary results of this sensitivity analysis led to the following ranking of FEAST models for future calibration and improvements: fuel conductivity, fission gas transport/release, fuel creep, and precipitation kinetics. More validation data is needed to validate calibrated parameter distributions for future uncertainty quantification studies with FEAST-Metal. Results of this study also served to point out some code deficiencies and possible errors, and these are being investigated in order to determine root causes and to improve upon the existing code models.

  5. Initial results from a multiple monoenergetic gamma radiography system for nuclear security

    Science.gov (United States)

    O'Day, Buckley E.; Hartwig, Zachary S.; Lanza, Richard C.; Danagoulian, Areg

    2016-10-01

    The detection of assembled nuclear devices and concealed special nuclear materials (SNM) such as plutonium or uranium in commercial cargo traffic is a major challenge in mitigating the threat of nuclear terrorism. Currently available radiographic and active interrogation systems use ∼1-10 MeV bremsstrahlung photon beams. Although simple to build and operate, bremsstrahlung-based systems deliver high radiation doses to the cargo and to potential stowaways. To eliminate problematic issues of high dose, we are developing a novel technique known as multiple monoenergetic gamma radiography (MMGR). MMGR uses ion-induced nuclear reactions to produce two monoenergetic gammas for dual-energy radiography. This allows us to image the areal density and effective atomic number (Zeff) of scanned cargo. We present initial results from the proof-of-concept experiment, which was conducted at the MIT Bates Research and Engineering Center. The purpose of the experiment was to assess the capabilities of MMGR to measure areal density and Zeff of container cargo mockups. The experiment used a 3.0 MeV radiofrequency quadrupole accelerator to create sources of 4.44 MeV and 15.11 MeV gammas from the 11B(d,nγ)12C reaction in a thick natural boron target; the gammas are detected by an array of NaI(Tl) detectors after transmission through cargo mockups . The measured fluxes of transmitted 4.44 MeV and 15.11 MeV gammas were used to assess the areal density and Zeff. Initial results show that MMGR is capable of discriminating the presence of high-Z materials concealed in up to 30 cm of iron shielding from low- and mid-Z materials present in the cargo mockup.

  6. What do Patients Want From Their Radiation Oncologist? Initial Results From a Prospective Trial

    International Nuclear Information System (INIS)

    Bhatnagar, Ajay K.; Land, Stephanie R.; Shogan, Alyson; Rodgers, Edwin E.; Heron, Dwight E.; Flickinger, John C.

    2007-01-01

    Purpose: To assess patients' initial physician preferences using a newly developed instrument. Methods and Materials: A total of 182 patients with a primary diagnosis of prostate, breast, or lung cancer referred for consultation to University of Pittsburgh Cancer Institute Department of Radiation Oncology enrolled in our institutional review board-approved protocol. All patients completed patient preference instrument surveys before meeting their radiation oncologist. Survey responses to 10 statements were categorized into three groups (agree, neutral, or disagree), and the association of survey responses by cancer site was tested with chi-squared tests. Results: Ninety-nine percent of all patients preferred to be addressed by their first name in encounters with their radiation oncologist. There were significant associations of Item 3 (hand holding) with gender (p = 0.039) and education (p = 0.028). The responses to Item 5, a statement that patients would feel uncomfortable if the radiation oncologist offered to hug them at the end of treatment, was significantly associated with disease site (p < 0.0001). Further analysis was performed for Item 5 and revealed that the male lung cancer patients had a much higher rate of disagreement with Item 5 compared with prostate cancer patients (37% vs. 18%). Conclusions: Results of this study may afford greater insight and foster better understanding of what patients want from their radiation oncologist. For breast, lung, and prostate cancer patients, initial preferences for their radiation oncologist are generally similar, according to this tool. However, there are important difference among cancer sites (and gender) regarding physical contact at the end of treatment

  7. Chronic Intermittent Hypoxia Induces Atherosclerosis

    OpenAIRE

    Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

    2007-01-01

    Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

  8. Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Stephan Niebler

    2015-01-01

    Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

  9. Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

    Directory of Open Access Journals (Sweden)

    Peter Vaupel

    2014-03-01

    Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

  10. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

    Directory of Open Access Journals (Sweden)

    Dirksen Uta

    2010-07-01

    Full Text Available Abstract Background Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor. Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. Methods HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. Results 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Conclusions Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

  11. 42 CFR 476.93 - Opportunity to discuss proposed initial denial determination and changes as a result of a DRG...

    Science.gov (United States)

    2010-10-01

    ... determination and changes as a result of a DRG validation. 476.93 Section 476.93 Public Health CENTERS FOR... initial denial determination and changes as a result of a DRG validation. Before a QIO reaches an initial denial determination or makes a change as a result of a DRG validation, it must— (a) Promptly notify the...

  12. 42 CFR 476.96 - Review period and reopening of initial denial determinations and changes as a result of DRG...

    Science.gov (United States)

    2010-10-01

    ... determinations and changes as a result of DRG validations. 476.96 Section 476.96 Public Health CENTERS FOR... initial denial determinations and changes as a result of DRG validations. (a) General timeframe. A QIO or... initial denial determination or a change as a result of a DRG validation. (b) Extended timeframes. (1) An...

  13. Hypoxia, Oxidative Stress and Fat

    Directory of Open Access Journals (Sweden)

    Nikolaus Netzer

    2015-06-01

    Full Text Available Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.

  14. Psychomotor skills learning under chronic hypoxia.

    Science.gov (United States)

    Bouquet, C A; Gardette, B; Gortan, C; Abraini, J H

    1999-09-29

    Psychomotor deficits are a prominent feature in subjects exposed to hypoxia. Eight subjects exposed to chronic hypoxia during a simulated climb to 8848 m (Everest-Comex 97) were investigated using both a simple psychomotor task (Purdue pegboard) and two complex psychomotor tasks including a recognition task of either a color stimulus (high semantic level) or an abstract sign (low semantic level). Exposure to hypoxic stress mainly produced psychomotor skills learning deficits compared to control study, with greater deficits in the complex psychomotor task. The pattern of results suggests disruptions of motor strategic process. Our data further suggest that the relative strength of implicit or automatic memory processes associated with semantic information processing may increase when disturbances occur in brain functions.

  15. Hypoxia tolerance in coral-reef triggerfishes (Balistidae)

    Science.gov (United States)

    Wong, Corrie C.; Drazen, Jeffrey C.; Callan, Chatham K.; Korsmeyer, Keith E.

    2018-03-01

    Despite high rates of photosynthetic oxygen production during the day, the warm waters of coral reefs are susceptible to hypoxia at night due to elevated respiration rates at higher temperatures that also reduce the solubility of oxygen. Hypoxia may be a challenge for coral-reef fish that hide in the reef to avoid predators at night. Triggerfishes (Balistidae) are found in a variety of reef habitats, but they also are known to find refuge in reef crevices and holes at night, which may expose them to hypoxic conditions. The critical oxygen tension ( P crit) was determined as the point below which oxygen uptake could not be maintained to support standard metabolic rate (SMR) for five species of triggerfish. The triggerfishes exhibited similar levels of hypoxia tolerance as other coral-reef and coastal marine fishes that encounter low oxygen levels in their environment. Two species, Rhinecanthus rectangulus and R. aculeatus, had the lowest P crit ( 3.0 kPa O2), comparable to the most hypoxia-tolerant obligate coral-dwelling gobies, while Odonus niger and Sufflamen bursa were moderately tolerant to hypoxia ( P crit 4.5 kPa), and Xanthichthys auromarginatus was intermediate ( P crit 3.7 kPa). These differences in P crit were not due to differences in oxygen demand, as all the species had a similar SMR once mass differences were taken into account. The results suggest that triggerfish species are adapted for different levels of hypoxia exposure during nocturnal sheltering within the reef.

  16. Hypoxia inhibits colonic ion transport via activation of AMP kinase.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    BACKGROUND AND AIMS: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport. METHODS: The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport. RESULTS: This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion. CONCLUSION: We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

  17. Radiation-induced hypoxia may perpetuate late normal tissue injury

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Anscher, Mitchell S.; Feng, Q.-F.; Rabbani, Zahid N.; Amin, Khalid; Samulski, Thaddeus S.; Dewhirst, Mark W.; Haroon, Zishan A.

    2001-01-01

    Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

  18. Intermittent Hypoxia in Childhood: The Harmful Consequences Versus Potential Benefits of Therapeutic Uses

    OpenAIRE

    Serebrovskaya, Tatiana V.; Xi, Lei

    2015-01-01

    Intermittent hypoxia often occurs in early infancy in both preterm and term infants and especially at 36 to 44 weeks postmenstrual age. These episodes of intermittent hypoxia could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of intermittent hypoxia on development, behavior, academic achievement and cognition in children with sleep apnea syndrome. It remains uncertain the exact causa...

  19. Initial results from the high resolution powder diffractometer HRPD at ISIS

    International Nuclear Information System (INIS)

    David, W.I.F.; Harrison, W.T.A.; Johnson, M.W.

    1986-07-01

    The paper reviews the initial commissioning of the high resolution time-of-flight neutron powder diffractometer, HRPD, on the Spallation Neutron Source, ISIS, at the Rutherford Appleton Laboratory. Preliminary results have confirmed both intensity and resolution predictions indicating that (Δd/d) lies between 0.04% and 0.08% for all d-spacings between 0.2 and 5A. The scientific potential of this increased resolution over existing time-of-flight diffractometers has been demonstrated in the successful ab initio structure determination of an unknown inorganic material, FeAsO 4 , and the detailed study of subtle symmetry changes in NiO. The true instrumental resolution, however, has been observed in only a small number of experiments: sample broadening is often seen to play a dominant role in the determination of the peak shape, particularly at longer d-spacings. This leads to additional useful information about macroscopic properties, such as anisotropic crystallite size, strain distribution and sample homogeneity, but also results in a significant increase in complexity of peak-shape description and data-analysis strategy. (author)

  20. Evaluation of wireless sensor networks (WSNs) for remote wetland monitoring: design and initial results.

    Science.gov (United States)

    Watras, Carl J; Morrow, Michael; Morrison, Ken; Scannell, Sean; Yaziciaglu, Steve; Read, Jordan S; Hu, Yu-Hen; Hanson, Paul C; Kratz, Tim

    2014-02-01

    Here, we describe and evaluate two low-power wireless sensor networks (WSNs) designed to remotely monitor wetland hydrochemical dynamics over time scales ranging from minutes to decades. Each WSN (one student-built and one commercial) has multiple nodes to monitor water level, precipitation, evapotranspiration, temperature, and major solutes at user-defined time intervals. Both WSNs can be configured to report data in near real time via the internet. Based on deployments in two isolated wetlands, we report highly resolved water budgets, transient reversals of flow path, rates of transpiration from peatlands and the dynamics of chromophoric-dissolved organic matter and bulk ionic solutes (specific conductivity)-all on daily or subdaily time scales. Initial results indicate that direct precipitation and evapotranspiration dominate the hydrologic budget of both study wetlands, despite their relatively flat geomorphology and proximity to elevated uplands. Rates of transpiration from peatland sites were typically greater than evaporation from open waters but were more challenging to integrate spatially. Due to the high specific yield of peat, the hydrologic gradient between peatland and open water varied with precipitation events and intervening periods of dry out. The resultant flow path reversals implied that the flux of solutes across the riparian boundary varied over daily time scales. We conclude that WSNs can be deployed in remote wetland-dominated ecosystems at relatively low cost to assess the hydrochemical impacts of weather, climate, and other perturbations.

  1. Initial results of tests of depth markers as a surface diagnostic for fusion devices

    Directory of Open Access Journals (Sweden)

    L.A. Kesler

    2017-08-01

    Full Text Available The Accelerator-Based In Situ Materials Surveillance (AIMS diagnostic was developed to perform in situ ion beam analysis (IBA on Alcator C-Mod in August 2012 to study divertor surfaces between shots. These results were limited to studying low-Z surface properties, because the Coulomb barrier precludes nuclear reactions between high-Z elements and the ∼1 MeV AIMS deuteron beam. In order to measure the high-Z erosion, a technique using deuteron-induced gamma emission and a low-Z depth marker is being developed. To determine the depth of the marker while eliminating some uncertainty due to beam and detector parameters, the energy dependence of the ratio of two gamma yields produced from the same depth marker will be used to determine the ion beam energy loss in the surface, and thus the thickness of the high-Z surface. This paper presents the results of initial trials of using an implanted depth marker layer with a deuteron beam and the method of ratios. First tests of a lithium depth marker proved unsuccessful due to the production of conflicting gamma peaks, among other issues. However, successful trials with a boron depth marker show that it is possible to measure the depth of the marker layer with the method of gamma yield ratios.

  2. [Implementation of a regional system for the emergency care of acute ischemic stroke: Initial results].

    Science.gov (United States)

    Soares-Oliveira, Miguel; Araújo, Fernando

    2014-06-01

    Implementing integrated systems for emergency care of patients with acute ischemic stroke helps reduce morbidity and mortality. We describe the process of organizing and implementing a regional system to cover around 3.7 million people and its main initial results. We performed a descriptive analysis of the implementation process and a retrospective analysis of the following parameters: number of patients prenotified by the pre-hospital system; number of times thrombolysis was performed; door-to-needle time; and functional assessment three months after stroke. The implementation process started in November 2005 and ended in December 2009, and included 11 health centers. There were 3574 prenotifications from the prehospital system. Thrombolysis was performed in 1142 patients. The percentage of patients receiving thrombolysis rose during the study period, with a maximum of 16%. Median door-to-needle time was 62 min in 2009. Functional recovery three months after stroke was total or near total in 50% of patients. The regional system implemented for emergency care of patients with acute ischemic stroke has led to health gains, with progressive improvements in patients' access to thrombolysis, and to greater equity in the health care system, thus helping to reduce mortality from cerebrovascular disease in Portugal. Our results, which are comparable with those of international studies, support the strategy adopted for implementation of this system. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  3. Epistemology and expectations survey about experimental physics: Development and initial results

    Directory of Open Access Journals (Sweden)

    Benjamin M. Zwickl

    2014-06-01

    Full Text Available In response to national calls to better align physics laboratory courses with the way physicists engage in research, we have developed an epistemology and expectations survey to assess how students perceive the nature of physics experiments in the contexts of laboratory courses and the professional research laboratory. The Colorado Learning Attitudes about Science Survey for Experimental Physics (E-CLASS evaluates students’ epistemology at the beginning and end of a semester. Students respond to paired questions about how they personally perceive doing experiments in laboratory courses and how they perceive an experimental physicist might respond regarding their research. Also, at the end of the semester, the E-CLASS assesses a third dimension of laboratory instruction, students’ reflections on their course’s expectations for earning a good grade. By basing survey statements on widely embraced learning goals and common critiques of teaching labs, the E-CLASS serves as an assessment tool for lab courses across the undergraduate curriculum and as a tool for physics education research. We present the development, evidence of validation, and initial formative assessment results from a sample that includes 45 classes at 20 institutions. We also discuss feedback from instructors and reflect on the challenges of large-scale online administration and distribution of results.

  4. Dual-energy contrast-enhanced digital mammography: initial clinical results

    International Nuclear Information System (INIS)

    Dromain, Clarisse; Thibault, Fabienne; Tardivon, Anne; Muller, Serge; Rimareix, Francoise; Delaloge, Suzette; Balleyguier, Corinne

    2011-01-01

    To assess the diagnostic accuracy of Dual-Energy Contrast-Enhanced Digital Mammography (CEDM) as an adjunct to mammography (MX) versus MX alone and versus mammography plus ultrasound (US). 120 women with 142 suspect findings on MX and/or US underwent CEDM. A pair of low- and high-energy images was acquired using a modified full-field digital mammography system. Exposures were taken in MLO at 2 min and in CC at 4 min after the injection of 1.5 ml/kg of an iodinated contrast agent. One reader evaluated MX, US and CEDM images during 2 sessions 1 month apart. Sensitivity, specificity, and area under the ROC curve were estimated. The results from pathology and follow-up identified 62 benign and 80 malignant lesions. Areas under the ROC curves were significantly superior for MX+CEDM than it was for MX alone and for MX+US using BI-RADS. Sensitivity was higher for MX+CEDM than it was for MX (93% vs. 78%; p < 0.001) with no loss in specificity. The lesion size was closer to the histological size for CEDM. All 23 multifocal lesions were correctly detected by MX+CEDM vs. 16 and 15 lesions by MX and US respectively. Initial clinical results show that CEDM has better diagnostic accuracy than mammography alone and mammography+ultrasound. (orig.)

  5. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor

    International Nuclear Information System (INIS)

    Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

    2010-01-01

    Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1α and HIF-2α immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1α-positive, 15 HIF-2α-positive and 10 positive for HIF-1α and HIF-2α. Expression of HIF-1α and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1α and HIF-2α in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2α in Ewing's. Downstream transcription was HIF-1α-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by ≥ 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1α and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas

  6. Hypoxia and hypoglycaemia in Ewing's sarcoma and osteosarcoma: regulation and phenotypic effects of Hypoxia-Inducible Factor.

    Science.gov (United States)

    Knowles, Helen J; Schaefer, Karl-Ludwig; Dirksen, Uta; Athanasou, Nicholas A

    2010-07-16

    Hypoxia regulates gene expression via the transcription factor HIF (Hypoxia-Inducible Factor). Little is known regarding HIF expression and function in primary bone sarcomas. We describe HIF expression and phenotypic effects of hypoxia, hypoglycaemia and HIF in Ewing's sarcoma and osteosarcoma. HIF-1alpha and HIF-2alpha immunohistochemistry was performed on a Ewing's tumour tissue array. Ewing's sarcoma and osteosarcoma cell lines were assessed for HIF pathway induction by Western blot, luciferase assay and ELISA. Effects of hypoxia, hypoglycaemia and isoform-specific HIF siRNA were assessed on proliferation, apoptosis and migration. 17/56 Ewing's tumours were HIF-1alpha-positive, 15 HIF-2alpha-positive and 10 positive for HIF-1alpha and HIF-2alpha. Expression of HIF-1alpha and cleaved caspase 3 localised to necrotic areas. Hypoxia induced HIF-1alpha and HIF-2alpha in Ewing's and osteosarcoma cell lines while hypoglycaemia specifically induced HIF-2alpha in Ewing's. Downstream transcription was HIF-1alpha-dependent in Ewing's sarcoma, but regulated by both isoforms in osteosarcoma. In both cell types hypoglycaemia reduced cellular proliferation by >or= 45%, hypoxia increased apoptosis and HIF siRNA modulated hypoxic proliferation and migration. Co-localisation of HIF-1alpha and necrosis in Ewing's sarcoma suggests a role for hypoxia and/or hypoglycaemia in in vivo induction of HIF. In vitro data implicates hypoxia as the primary HIF stimulus in both Ewing's and osteosarcoma, driving effects on proliferation and apoptosis. These results provide a foundation from which to advance understanding of HIF function in the pathobiology of primary bone sarcomas.

  7. Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

    LENUS (Irish Health Repository)

    McEvoy, Lynda M

    2015-01-01

    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.

  8. Factors to Consider in Selecting an Organisational Improvement Initiative: Survey Results

    Directory of Open Access Journals (Sweden)

    Mohammad Musli

    2017-01-01

    Full Text Available Organisations should select the appropriate improvement initiative that will fit with the context of organisation and provide value to the organisation. This paper presents 18 factors to be considered when selecting an organisational improvement initiative. Organisational improvement initiatives are approaches, management systems, tools and/or techniques that can be used for managing and improving organisations, such as Lean, ISO9001, Six Sigma and Improvement Team. A survey was conducted to identify the level of importance of these 18 factors as criteria for selecting an improvement initiative. Purposive sampling was used for this survey involving practitioners, managers, engineers, executives, consultants and/or academicians, who have been involved in the selection and/or implementation of organisational improvement initiatives in Malaysia. Two factors were rated as ‘very high importance’, which involve: (1 The ability to gain top management commitment and support to introduce and implement the initiative successfully, and (2 The initiative is aligned to the vision, mission and/or purpose of the organisation. All these factors can be adopted by the organisations as decision criteria to assist in the selection of the most appropriate improvement initiative based on rational decision making.

  9. Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications.

    Science.gov (United States)

    Vaupel, Peter; Mayer, Arnulf

    2014-01-01

    Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.

  10. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

    Directory of Open Access Journals (Sweden)

    Joffrey ePelletier

    2012-02-01

    Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

  11. Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia

    Directory of Open Access Journals (Sweden)

    C.B. Sacramento

    2010-08-01

    Full Text Available The main objective of the present study was to find suitable DNA-targeting sequences (DTS for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS and hypoxia-responsive element (HRE sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF. The rate of plasmid nuclear transport and consequent gene expression under normoxia (20% O2 and hypoxia (less than 5% O2 were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50% lower under hypoxia, while the HRE plasmid was about 50% higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.

  12. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

    Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

  13. Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Joffrey; Bellot, Grégory [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France); Gounon, Pierre; Lacas-Gervais, Sandra [Centre Commun de Microscopie Appliquée, University of Nice-Sophia Antipolis, Nice (France); Pouysségur, Jacques; Mazure, Nathalie M., E-mail: mazure@unice.fr [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France)

    2012-02-28

    The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO{sub 2} acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

  14. Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

    International Nuclear Information System (INIS)

    Pelletier, Joffrey; Bellot, Grégory; Gounon, Pierre; Lacas-Gervais, Sandra; Pouysségur, Jacques; Mazure, Nathalie M.

    2012-01-01

    The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO 2 acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

  15. Research Initiatives and Preliminary Results In Automation Design In Airspace Management in Free Flight

    Science.gov (United States)

    Corker, Kevin; Lebacqz, J. Victor (Technical Monitor)

    1997-01-01

    The NASA and the FAA have entered into a joint venture to explore, define, design and implement a new airspace management operating concept. The fundamental premise of that concept is that technologies and procedures need to be developed for flight deck and ground operations to improve the efficiency, the predictability, the flexibility and the safety of airspace management and operations. To that end NASA Ames has undertaken an initial development and exploration of "key concepts" in the free flight airspace management technology development. Human Factors issues in automation aiding design, coupled aiding systems between air and ground, communication protocols in distributed decision making, and analytic techniques for definition of concepts of airspace density and operator cognitive load have been undertaken. This paper reports the progress of these efforts, which are not intended to definitively solve the many evolving issues of design for future ATM systems, but to provide preliminary results to chart the parameters of performance and the topology of the analytic effort required. The preliminary research in provision of cockpit display of traffic information, dynamic density definition, distributed decision making, situation awareness models and human performance models is discussed as they focus on the theme of "design requirements".

  16. Cosmic noise absorption and ionospheric currents at the South Pole and Frobisher Bay: Initial results

    International Nuclear Information System (INIS)

    Rosenberg, T.J.; Wolfe, A.; Lanzerotti, L.J.

    1987-01-01

    Studies of the conjugacy of auroral and ionospheric phenomena at very high latitudes are an important aspect of magnetospheric physics research. The extent to which auroral phenomena in opposite hemispheres are similar in occurrence and in the details of their temporal, spatial, and spectral characteristics can be used to infer the commonality of the source(s) of the disturbances. At one extreme in this consideration is the questions of whether sources lie on open or closed magnetic field lines. The University of Maryland and AT ampersand T Bell Laboratories have operated riometers and fluxgate magnetometers, respectively, at South Pole since 1982. Corresponding measurements at Frobisher Bay were begun in mid-1985. Riometers record the absorption of cosmic radio noise in the ionosphere produced by the enhances precipitation of energetic charged particles. The studies of the riometer data relate mainly to the effects of the influx of magnetospheric electrons, which give rise to auroral absorption of the cosmic signals. Intense currents (electrojets) that often flow in the ionosphere in association with auroral absorption events produce magnetic field changes that can be recorded on the ground by appropriately sited magnetometers. This report presents some initial results of the comparison of the two data sets

  17. Exploration of Compact Stellarators as Power Plants: Initial Results from ARIES-CS Study

    International Nuclear Information System (INIS)

    Najmabadi, Farrokh

    2005-01-01

    A detailed and integrated study of compact stellarators as power plants, ARIES-CS, was initiated recently to advance our understanding of attractive compact stellarator configurations and to define key R and D areas. We have completed phase 1 of ARIES-CS study - our results are described in this paper. We have identified several promising stellarator configurations. High α particle loss of these configurations is a critical issue. It appears that devices with an overall size similar to those envisioned for tokamak power plants are possible. A novel approach was developed in ARIES-CS in which the blanket at the critical areas of minimum stand-off is replaced by a highly efficient WC-based shield. In this manner, we have been able to reduce the minimum stand-off by ∼20%-30% compared to a uniform radial build which was assumed in previous studies. Our examination of engineering options indicates that overall assembly and maintenance procedure plays a critical role in identifying acceptable engineering design and has a major impact on the optimization of a plasma/coil configuration

  18. Initial results from the rebuilt EXTRAP T2R RFP device

    Science.gov (United States)

    Brunsell, P. R.; Bergsåker, H.; Cecconello, M.; Drake, J. R.; Gravestijn, R. M.; Hedqvist\\ad{2 }, A.; Malmberg, J.-A.

    2001-11-01

    The EXTRAP T2R thin shell reversed-field pinch (RFP) device has recently resumed operation after a major rebuild including the replacement of the graphite armour with molybdenum limiters, a fourfold increase of the shell time constant, and the replacement of the helical coil used for the toroidal field with a conventional solenoid-type coil. Wall-conditioning using hydrogen glow discharge cleaning was instrumental for successful RFP operation. Carbon was permanently removed from the walls during the first week of operation. The initial results from RFP operation with relatively low plasma currents in the range Ip = 70-100 kA are reported. RFP discharges are sustained for more than three shell times. Significant improvements in plasma parameters are observed, compared to operation before the rebuild. There is a substantial reduction in the carbon impurity level. The electron density behaviour is more shot-to-shot reproducible. The typical density is ne = 0.5-1×1019 m-3. Monitors of Hα line radiation indicate that the plasma wall interaction is more toroidally symmetric and that there is less transient gas release from the wall. The minimum loop voltage is in the range Vt = 28-35 V, corresponding to a reduction by a factor of two to three compared to the value before the rebuild.

  19. Susceptibility weighted imaging (SWI) of the kidney at 3 T. Initial results

    International Nuclear Information System (INIS)

    Mie, Moritz B.; Zoellner, Frank G.; Heilmann, Melanie; Schad, Lothar R.; Nissen, Johanna C.; Schoenberg, Stefan O.; Michaely, Henrik J.

    2010-01-01

    Susceptibility weighted imaging provides diagnostic information in strokes, hemorrhages, and cerebral tumors and has proven to be a valuable tool in imaging venous vessels in the cerebrum. The SWI principle is based on the weighting of T 2 * weighted magnitude images with a phase mask, therewith improving image contrast of veins or neighbouring structures of different susceptibility, in general. T 2 * weighted MRI is already used for assessment of kidney function. In this paper, the feasibility of SWI on kidneys was investigated. Translation of SWI from the brain to the kidneys comes along with two main challenges: (i) organ motion due to breathing and (ii) a higher oxygenation level of renal veins compared to the brain. To handle these problems, the acquisition time has been cut down to allow for breath-hold examinations, and different post-processing methods including a new phase mask were investigated to visualize renal veins. Results showed that by a new post-processing strategy SWI contrast was enhanced on average by a factor of 1.33 compared to the standard phase mask. In summary, initial experiences of SWI on the kidneys demonstrated the feasibility. However, further technical developments have to be performed to make this technology applicable in clinical abdominal MRI. (orig.)

  20. Initial results of local grid control using wind farms with grid support

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, Poul; Hansen, Anca D.; Iov, F.; Blaabjerg, F.

    2005-09-01

    This report describes initial results with simulation of local grid control using wind farms with grid support. The focus is on simulation of the behaviour of the wind farms when they are isolated from the main grid and establish a local grid together with a few other grid components. The isolated subsystems used in the work presented in this report do not intend to simulate a specific subsystem, but they are extremely simplified single bus bar systems using only a few more components than the wind farm. This approach has been applied to make it easier to understand the dynamics of the subsystem. The main observation is that the fast dynamics of the wind turbines seem to be able to contribute significantly to the grid control, which can be useful where the wind farm is isolated with a subsystem from the main grid with surplus of generation. Thus, the fast down regulation of the wind farm using automatic frequency control can keep the subsystem in operation and thereby improve the reliability of the grid. (LN)

  1. Initial Results of the SSPX Transient Internal Probe System for Measuring Toroidal Field Profiles

    Science.gov (United States)

    Holcomb, C. T.; Jarboe, T. R.; Mattick, A. T.; Hill, D. N.; McLean, H. S.; Wood, R. D.; Cellamare, V.

    2000-10-01

    Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. The Sustained Spheromak Physics Experiment (SSPX) is using a field profile diagnostic called the Transient Internal Probe (TIP). TIP consists of a verdet-glass bullet that is used to measure the magnetic field by Faraday rotation. This probe is shot through the spheromak by a light gas gun at speeds near 2 km/s. An argon laser is aligned along the path of the probe. The light passes through the probe and is retro-reflected to an ellipsometer that measures the change in polarization angle. The measurement is spatially resolved down to the probes’ 1 cm length to within 15 Gauss. Initial testing results are given. This and future data will be used to determine the field profile for equilibrium reconstruction. TIP can also be used in conjunction with wall probes to map out toroidal mode amplitudes and phases internally. This work was performed under the auspices of US DOE by the University of California Lawrence Livermore National Laboratory under Contract No. W-7405-ENG-48.

  2. Project CONVERGE: Initial Results From the Mapping of Surface Currents in Palmer Deep

    Science.gov (United States)

    Statscewich, H.; Kohut, J. T.; Winsor, P.; Oliver, M. J.; Bernard, K. S.; Cimino, M. A.; Fraser, W.

    2016-02-01

    The Palmer Deep submarine canyon on the Western Antarctic Peninsula provides a conduit for upwelling of relatively warm, nutrient rich waters which enhance local primary production and support a food web productive enough to sustain a large top predator biomass. In an analysis of ten years of satellite-tagged penguins, Oliver et al. (2013) showed that circulation features associated with tidal flows may be a key driver of nearshore predator distributions. During diurnal tides, the penguins feed close to their breeding colonies and during semi-diurnal tides, the penguins make foraging trips to the more distant regions of Palmer Deep. It is hypothesized that convergent features act to concentrate primary producers and aggregate schools of krill that influence the behavior of predator species. The initial results from a six month deployment of a High Frequency Radar network in Palmer Deep are presented in an attempt to characterize and quantify convergent features. During a three month period from January through March 2015, we conducted in situ sampling consisting of multiple underwater glider deployments, small boat acoustic surveys of Antarctic krill, and penguin ARGOS-linked satellite telemetry and time-depth recorders (TDRs). The combination of real-time surface current maps with adaptive in situ sampling introduces High Frequency Radar to the Antarctic in a way that allows us to rigorously and efficiently test the influence of local tidal processes on top predator foraging ecology.

  3. Energetic neutral atom imaging with the Polar CEPPAD/IPS instrument: Initial forward modeling results

    International Nuclear Information System (INIS)

    Henderson, M.G.; Reeves, G.D.; Moore, K.R.; Spence, H.E.; Jorgensen, A.M.; Roelof, E.C.

    1997-01-01

    Although the primary function of the CEP-PAD/IPS instrument on Polar is the measurement of energetic ions in-situ, it has also proven to be a very capable Energetic neutral Atom (ENA) imager. Raw ENA images are currently being constructed on a routine basis with a temporal resolution of minutes during both active and quiet times. However, while analyses of these images by themselves provide much information on the spatial distribution and dynamics of the energetic ion population in the ring current, detailed modeling is required to extract the actual ion distributions. In this paper, the authors present the initial results of forward modeling an IPS ENA image obtained during a small geo-magnetic storm on June 9, 1997. The equatorial ion distribution inferred with this technique reproduces the expected large noon/midnight and dawn/dusk asymmetries. The limitations of the model are discussed and a number of modifications to the basic forward modeling technique are proposed which should significantly improve its performance in future studies

  4. Underground storage at Saint-Illiers-la-Ville. Initial results of filling. Reservoir control problems

    Energy Technology Data Exchange (ETDEWEB)

    Vernet, D

    1968-01-01

    The underground storage at Saint-Illiers-la-Ville (Yvelines in the Paris area) was discussed by Toche at the time when it was filled with gas in 1965. Now, 2-1/2 yr after the initial input, the volume of storage has reached 500 million cu m, and the first industrial withdrawals took place during the winter of 1967-1968. The results obtained in the operation of this underground storage are extremely satisfactory. In spite of differences in the composition of the sand layer, the gas bubble developed in a very regular way, horizontally and vertically, and the full penetration well equipment made a high output rate easy to obtain. Reservoir control was handled efficiently and the movements of the bubble contour were shown for every fluctuation of the injection and withdrawal volumes. Tests for production capacity showed the low extent to which the wells were affected by the phenomenon of water- coning and indicated measures to be taken to prevent the formation of hydrates. The measures effected and the conclusions which can be derived are discussed.

  5. Initial Results of Optical Vortex Laser Absorption Spectroscopy in the HYPER-I Device

    Science.gov (United States)

    Yoshimura, Shinji; Asai, Shoma; Aramaki, Mitsutoshi; Terasaka, Kenichiro; Ozawa, Naoya; Tanaka, Masayoshi; Morisaki, Tomohiro

    2015-11-01

    Optical vortex beams have a potential to make a new Doppler measurement, because not only parallel but perpendicular movement of atoms against the beam axis causes the Doppler shift of their resonant absorption frequency. As the first step of a proof-of-principle experiment, we have performed the optical vortex laser absorption spectroscopy for metastable argon neutrals in an ECR plasma produced in the HYPER-I device at the National Institute for Fusion Science, Japan. An external cavity diode laser (TOPTICA, DL100) of which center wavelength was 696.735 nm in vacuum was used for the light source. The Hermite-Gaussian (HG) beam was converted into the Laguerre-Gaussian (LG) beam (optical vortex) by a computer-generated hologram displayed on the spatial light modulator (Hamamatsu, LCOS-SLM X10468-07). In order to make fast neutral flow across the LG beam, a high speed solenoid valve system was installed on the HYPER-I device. Initial results including the comparison of absorption spectra for HG and LG beams will be presented. This study was supported by NINS young scientists collaboration program for cross-disciplinary study, NIFS collaboration research program (NIFS13KOAP026), and JSPS KAKENHI grant number 15K05365.

  6. Communications with Mars During Periods of Solar Conjunction: Initial Study Results

    Science.gov (United States)

    Morabito, D.; Hastrup, R.

    2001-07-01

    During the initial phase of the human exploration of Mars, a reliable communications link to and from Earth will be required. The direct link can easily be maintained during most of the 780-day Earth-Mars synodic period. However, during periods in which the direct Earth-Mars link encounters increased intervening charged particles during superior solar conjunctions of Mars, the resultant effects are expected to corrupt the data signals to varying degrees. The purpose of this article is to explore possible strategies, provide recommendations, and identify options for communicating over this link during periods of solar conjunctions. A significant improvement in telemetry data return can be realized by using the higher frequency 32 GHz (Ka-band), which is less susceptible to solar effects. During the era of the onset of probable human exploration of Mars, six superior conjunctions were identified from 2015 to 2026. For five of these six conjunctions, where the signal source is not occulted by the disk of the Sun, continuous communications with Mars should be achievable. Only during the superior conjunction of 2023 is the signal source at Mars expected to lie behind the disk of the Sun for about one day and within two solar radii (0. 5 deg) for about three days.

  7. Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

    Science.gov (United States)

    Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

    2017-06-01

    Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.

  8. 42 CFR 476.94 - Notice of QIO initial denial determination and changes as a result of a DRG validation.

    Science.gov (United States)

    2010-10-01

    ... changes as a result of a DRG validation. 476.94 Section 476.94 Public Health CENTERS FOR MEDICARE... changes as a result of a DRG validation. (a) Notice of initial denial determination—(1) Parties to be... retrospective review, (excluding DRG validation and post procedure review), within 3 working days of the initial...

  9. The Satellite based Monitoring Initiative for Regional Air quality (SAMIRA): Project summary and first results

    Science.gov (United States)

    Schneider, Philipp; Stebel, Kerstin; Ajtai, Nicolae; Diamandi, Andrei; Horalek, Jan; Nemuc, Anca; Stachlewska, Iwona; Zehner, Claus

    2017-04-01

    We present a summary and some first results of a new ESA-funded project entitled Satellite based Monitoring Initiative for Regional Air quality (SAMIRA), which aims at improving regional and local air quality monitoring through synergetic use of data from present and upcoming satellite instruments, traditionally used in situ air quality monitoring networks and output from chemical transport models. Through collaborative efforts in four countries, namely Romania, Poland, the Czech Republic and Norway, all with existing air quality problems, SAMIRA intends to support the involved institutions and associated users in their national monitoring and reporting mandates as well as to generate novel research in this area. The primary goal of SAMIRA is to demonstrate the usefulness of existing and future satellite products of air quality for improving monitoring and mapping of air pollution at the regional scale. A total of six core activities are being carried out in order to achieve this goal: Firstly, the project is developing and optimizing algorithms for the retrieval of hourly aerosol optical depth (AOD) maps from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) onboard of Meteosat Second Generation. As a second activity, SAMIRA aims to derive particulate matter (PM2.5) estimates from AOD data by developing robust algorithms for AOD-to-PM conversion with the support from model- and Lidar data. In a third activity, we evaluate the added value of satellite products of atmospheric composition for operational European-scale air quality mapping using geostatistics and auxiliary datasets. The additional benefit of satellite-based monitoring over existing monitoring techniques (in situ, models) is tested by combining these datasets using geostatistical methods and demonstrated for nitrogen dioxide (NO2), sulphur dioxide (SO2), and aerosol optical depth/particulate matter. As a fourth activity, the project is developing novel algorithms for downscaling coarse

  10. Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression.

    Science.gov (United States)

    Serebrovska, Tetiana V; Portnychenko, Alla G; Drevytska, Tetiana I; Portnichenko, Vladimir I; Xi, Lei; Egorov, Egor; Gavalko, Anna V; Naskalova, Svitlana; Chizhova, Valentina; Shatylo, Valeriy B

    2017-09-01

    The present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1α (HIF-1α) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1α mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1α target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1α was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes. Impact statement The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1α mRNA expressions as well as its target genes, which were positively correlated with higher tolerance

  11. Hypoxia in the changing marine environment

    International Nuclear Information System (INIS)

    Zhang, J; Cowie, G; Naqvi, S W A

    2013-01-01

    The predicted future of the global marine environment, as a combined result of forcing due to climate change (e.g. warming and acidification) and other anthropogenic perturbation (e.g. eutrophication), presents a challenge to the sustainability of ecosystems from tropics to high latitudes. Among the various associated phenomena of ecosystem deterioration, hypoxia can cause serious problems in coastal areas as well as oxygen minimum zones in the open ocean (Diaz and Rosenberg 2008 Science 321 926–9, Stramma et al 2008 Science 320 655–8). The negative impacts of hypoxia include changes in populations of marine organisms, such as large-scale mortality and behavioral responses, as well as variations of species distributions, biodiversity, physiological stress, and other sub-lethal effects (e.g. growth and reproduction). Social and economic activities that are related to services provided by the marine ecosystems, such as tourism and fisheries, can be negatively affected by the aesthetic outcomes as well as perceived or real impacts on seafood quality (STAP 2011 (Washington, DC: Global Environment Facility) p 88). Moreover, low oxygen concentration in marine waters can have considerable feedbacks to other compartments of the Earth system, like the emission of greenhouse gases to the atmosphere, and can affect the global biogeochemical cycles of nutrients and trace elements. It is of critical importance to prediction and adaptation strategies that the key processes of hypoxia in marine environments be precisely determined and understood (cf Zhang et al 2010 Biogeosciences 7 1–24). (synthesis and review)

  12. Hypoxia in the changing marine environment

    Science.gov (United States)

    Zhang, J.; Cowie, G.; Naqvi, S. W. A.

    2013-03-01

    The predicted future of the global marine environment, as a combined result of forcing due to climate change (e.g. warming and acidification) and other anthropogenic perturbation (e.g. eutrophication), presents a challenge to the sustainability of ecosystems from tropics to high latitudes. Among the various associated phenomena of ecosystem deterioration, hypoxia can cause serious problems in coastal areas as well as oxygen minimum zones in the open ocean (Diaz and Rosenberg 2008 Science 321 926-9, Stramma et al 2008 Science 320 655-8). The negative impacts of hypoxia include changes in populations of marine organisms, such as large-scale mortality and behavioral responses, as well as variations of species distributions, biodiversity, physiological stress, and other sub-lethal effects (e.g. growth and reproduction). Social and economic activities that are related to services provided by the marine ecosystems, such as tourism and fisheries, can be negatively affected by the aesthetic outcomes as well as perceived or real impacts on seafood quality (STAP 2011 (Washington, DC: Global Environment Facility) p 88). Moreover, low oxygen concentration in marine waters can have considerable feedbacks to other compartments of the Earth system, like the emission of greenhouse gases to the atmosphere, and can affect the global biogeochemical cycles of nutrients and trace elements. It is of critical importance to prediction and adaptation strategies that the key processes of hypoxia in marine environments be precisely determined and understood (cf Zhang et al 2010 Biogeosciences 7 1-24).

  13. Intrauterine hypoxia: clinical consequences and therapeutic perspectives

    Directory of Open Access Journals (Sweden)

    Thompson LP

    2015-09-01

    Full Text Available Loren P Thompson,1 Sarah Crimmins,1 Bhanu P Telugu,2 Shifa Turan1 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; 2Department of Animal Sciences, University of Maryland, College Park, MD, USA Abstract: Intrauterine hypoxia is a significant clinical challenge in obstetrics that affects both the pregnant mother and fetus. Intrauterine hypoxia can occur in pregnant women living at high altitude and/or with cardiovascular disease. In addition, placental hypoxia can be generated by altered placental development and spiral artery remodeling leading to placental insufficiency and dysfunction. Both conditions can impact normal maternal cardiovascular homeostasis leading to preeclampsia and/or impair transfer of O2/nutrient supply resulting in fetal growth restriction. This review discusses the mechanisms underlying altered placental vessel remodeling, maternal and fetal consequences, patient management, and potential future therapies for improving these conditions. Keywords: fetal growth restriction, oxidative stress, extravillous trophoblast invasion, Doppler ultrasound, pulsatility index, preeclampsia 

  14. Design of and initial results from a Highly Instrumented Reactor for Atmospheric Chemistry (HIRAC

    Directory of Open Access Journals (Sweden)

    D. R. Glowacki

    2007-10-01

    Full Text Available The design of a Highly Instrumented Reactor for Atmospheric Chemistry (HIRAC is described and initial results obtained from HIRAC are presented. The ability of HIRAC to perform in-situ laser-induced fluorescence detection of OH and HO2 radicals with the Fluorescence Assay by Gas Expansion (FAGE technique establishes it as internationally unique for a chamber of its size and pressure/temperature variable capabilities. In addition to the FAGE technique, HIRAC features a suite of analytical instrumentation, including: a multipass FTIR system; a conventional gas chromatography (GC instrument and a GC instrument for formaldehyde detection; NO/NO2, CO, O3, and H2O vapour analysers. Ray tracing simulations and NO2 actinometry have been utilized to develop a detailed model of the radiation field within HIRAC. Comparisons between the analysers and the FTIR coupled to HIRAC have been performed, and HIRAC has also been used to investigate pressure dependent kinetics of the chlorine atom reaction with ethene and the reaction of O3 and t-2-butene. The results obtained are in good agreement with literature recommendations and Master Chemical Mechanism predictions. HIRAC thereby offers a highly instrumented platform with the potential for: (1 high precision kinetics investigations over a range of atmospheric conditions; (2 detailed mechanism development, significantly enhanced according to its capability for measuring radicals; and (3 field instrument intercomparison, calibration, development, and investigations of instrument response at a range of atmospheric conditions.

  15. Initial Surgical Experience with Aortic Valve Repair: Clinical and Echocardiographic Results

    Directory of Open Access Journals (Sweden)

    Francisco Diniz Affonso da Costa

    Full Text Available Abstract Introduction: Due to late complications associated with the use of conventional prosthetic heart valves, several centers have advocated aortic valve repair and/or valve sparing aortic root replacement for patients with aortic valve insufficiency, in order to enhance late survival and minimize adverse postoperative events. Methods: From March/2012 thru March 2015, 37 patients consecutively underwent conservative operations of the aortic valve and/or aortic root. Mean age was 48±16 years and 81% were males. The aortic valve was bicuspid in 54% and tricuspid in the remaining. All were operated with the aid of intraoperative transesophageal echocardiography. Surgical techniques consisted of replacing the aortic root with a Dacron graft whenever it was dilated or aneurysmatic, using either the remodeling or the reimplantation technique, besides correcting leaflet prolapse when present. Patients were sequentially evaluated with clinical and echocardiographic studies and mean follow-up time was 16±5 months. Results: Thirty-day mortality was 2.7%. In addition there were two late deaths, with late survival being 85% (CI 95% - 68%-95% at two years. Two patients were reoperated due to primary structural valve failure. Freedom from reoperation or from primary structural valve failure was 90% (CI 95% - 66%-97% and 91% (CI 95% - 69%-97% at 2 years, respectively. During clinical follow-up up to 3 years, there were no cases of thromboembolism, hemorrhage or endocarditis. Conclusions: Although this represents an initial series, these data demonstrates that aortic valve repair and/or valve sparing aortic root surgery can be performed with satisfactory immediate and short-term results.

  16. Initial Results from the STEM Student Experiences Aboard Ships (STEMSEAS) Program

    Science.gov (United States)

    Lewis, J. C.; Cooper, S. K.; Thomson, K.; Rabin, B.; Alberts, J.

    2016-12-01

    The Science Technology Engineering and Math Student Experiences Aboard Ships (STEMSEAS) program was created as a response to NSF's call (through GEOPATHS) for improving undergraduate STEM education and enhancing diversity in the geosciences. It takes advantage of unused berths on UNOLS ships during transits between expeditions. During its 2016 pilot year - which consisted of three transits on three different research vessels in different parts of the country, each with a slightly different focus - the program has gained significant insights into how best to create and structure these opportunities and create impact on individual students. A call for applications resulted in nearly 900 applicants for 30 available spots. Of these applicants, 32% are from minority groups underrepresented in the geosciences (Black, Hispanic, or American Indian) and 20% attend community colleges. The program was able to sail socioeconomically diverse cohorts and include women, veterans, and students with disabilities and from two- and four-year colleges. Twenty-three are underrepresented minorities, 6 attend community colleges, 5 attend an HBCU or tribal college, and many are at HSIs or other MSIs. While longer term impact assessment will have to wait, initial results and 6-month tracking for the first cohort indicate that these kinds of relatively short but intense experiences can indeed achieve significant impacts on students' perception of the geosciences, in their understanding of STEM career opportunities, their desire to work in a geoscience lab setting, and to incorporate geosciences into non-STEM careers. Insights were also gained into the successful makeup of mentor/leader groups, factors to consider in student selection, necessary pre- and post-cruise logistics management, follow-up activities, structure of activities during daily life at sea, increasing student networks and access to mentorships, and leveraging of pre-existing resources and ship-based opportunities

  17. Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study1234

    Science.gov (United States)

    Orchard, Tonya S; Larson, Joseph C; Alghothani, Nora; Bout-Tabaku, Sharon; Cauley, Jane A; Chen, Zhao; LaCroix, Andrea Z; Wactawski-Wende, Jean; Jackson, Rebecca D

    2014-01-01

    Background: Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear. Objective: We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD). Design: This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants. Results: Baseline hip BMD was 3% higher (P 422.5 compared with magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:24500155

  18. The IGAC activity for the development of global emissions inventories: Description and initial results

    International Nuclear Information System (INIS)

    Benkovitz, C.M.; Graedel, T.E.

    1992-02-01

    Modeling assessments of the atmospheric chemistry, air quality and climatic conditions of the past, present and future require as input inventories of emissions of the appropriate chemical species constructed on appropriate spatial and temporal scales. The task of the Global Emissions Inventories Activity (GEIA) of the International Global Atmospheric Chemistry Project (IGAC) is the production of global inventories suitable for a range of research applications. Current GEIA programs are generally based on addressing emissions by species; these include CO 2 , NH 3 /N 2 O, SO 2 /NO x , CFC, volatile organic compounds and radioisotopes. In addition a separate program to inventory emissions from biomass burning is also being structured, plus an additional program to address data management issues for all the developing inventories. Program priorities are based on current knowledge and tasks needed to produce the desired inventories. This paper will discuss the different types of global inventories to be developed by the GEIA programs, their key characteristics, and areas to be addressed in the compilation of such inventories. Results of the first GEIA task, a survey of existing inventories and auxiliary data, will be presented. The survey included status assessments for the available inventory information for nineteen different atmospheric species or groups of species on global and regional scales and over time. Of this entire body of information, the only inventory regarded as satisfactory was that for the global emissions of CFCs. An implication of the results of these assessments is that properly gridded emissions inventories are badly needed to support atmospheric modeling calculations on a variety of spatial and temporal scales. Initial studies in the development of global inventories of sulfur dioxide, currently the most advanced GEIA program, will be presented and discussed

  19. Nitroimidazoles and imaging hypoxia

    International Nuclear Information System (INIS)

    Nunn, A.; Linder, K.; Strauss, H.W.

    1995-01-01

    A class of compounds known to undergo different intracellular metabolism depending on the availability of oxygen in tissue, the nitroimidazoles, have been advocated for imaging hypoxic tissue. In the presence of normal oxygen levels the molecule is immediately reoxidized. In hypoxic tissue the low oxygen concentration is not able to effectively compete to reoxidize the molecule and further reduction appears to take place. The association is not irreversible. Nitroimidazoles for in vivo imaging using radiohalogenated derivatives of misonidazole have recently been employed in patients. Two major problems with fluoromisonidazole are its relatively low concentration within the lesion and the need to wait several hours to permit clearance of the agent from the normoxic background tissue. Even with high-resolution positron emission tomographic imaging, this combination of circumstances makes successful evaluation of hypoxic lesions a challenge. Single-photon agents, with their longer half-lives and comparable biological properties, offer a greater opportunity for successful imaging. In 1992 technetium-99m labeled nitroimidazoles were described that seem to have at least comparable in vivo characteristics. Laboratory studies have demonstrated preferential binding of these agents to hypoxic tissue in the myocardium, in the brain, and in tumors. These investigations indicate that imaging can provide direct evidence of tissue with low oxygen levels that is viable. Even from this early vantage point the utility of measuring tissue oxygen levels with external imaging suggests that hypoxia imaging could play a major role in clinical decision making. (orig./MG)

  20. Morphological state of aorta in the fetuses and newborns suffered from chronic intrauterine hypoxia (experimental research

    Directory of Open Access Journals (Sweden)

    O. V. Kaluzhina

    2015-04-01

    Full Text Available The cardiovascular system in newborns with chronic hypoxia is affected in 40–70%. Aim. To investigate morphological state of aorta in the fetuses and newborns suffered from chronic intrauterine hypoxia. Methods and results. Aortic wall was investigated with modern morphological methods in 34 laboratory animals in order to identify the morphological features of the fetuses and newborns’ vessel affected by this pathogenic factor. It was established that chronic hypoxia leads to endothelial trophics deterioration, its flattening, dystrophic processes with following cells desquamation, density reduction of smooth muscle cells, thickening of the intima-media. Conclusion. It shows alterative-sclerotic changes in aorta in cases with chronic hypoxia influence.

  1. Initial clinical results of linac stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for pituitary adenomas

    International Nuclear Information System (INIS)

    Mitsumori, Michihide; Shrieve, Dennis C.; Alexander, Eben; Kaiser, Ursula B.; Richardson, Gary E.; McL Black, Peter; Loeffler, Jay S.

    1997-01-01

    Purpose: To evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor control and toxicity of the treatment, thus evaluate the feasibility of these technique for the treatment of pituitary adenomas. Subjects and Methods: 48 patients with either inoperable, recurrent or residual pituitary adenoma who underwent either SRS or SRT at the Brigham and Women's Hospital between 9/89 and 9/95 were analyzed. Of these, 18 received treatment with SRS, and 30 received SRT. SRS was contraindicated for the patients in whom the minimal distance of the target and optic chiasm or optic nerve was less than 5 mm. Patient characteristics were similar in the two groups, with the exception of tumor volume and previous irradiation. Median tumor volumes were 1.8 cm 3 and 7.7 cm 3 for SRS and SRT, respectively. Three of the SRS and none of the SRT patients had a history of previous external radiation therapy. Both SRS and SRT were performed by the use of dedicated stereotactic 6-MV linear accelerator with a treatment plan designed using a dedicated software. Doses were prescribed to the isodose distribution that covered the identified target. Dose and normalization used for SRS varied from 1000 cGy at 85 % isodose line to 1800 cGy at 80 % isodose line. For SRT patients, total dose of 4500 cGy was normalized at 90 or 95 % isodose line and this was delivered in 25 fractions of 180 cGy daily dose. Results: Local control: There was 1 case of local failure in each of SRS and SRT series (median follow up 42.5 months and 22 month, respectively). CNS adverse effects: There were 3 SRS cases in whom a ring enhancement in the temporal lobe was observed in follow-up MRI. (median follow up 32 months). Of these, one resolved spontaneously, whereas the other 2 lesion persisted and considered to be radiation necrosis. None of them required surgical intervention to date. These were observed in the

  2. Transanal minimally-invasive surgery (TAMIS: Technique and results from an initial experience

    Directory of Open Access Journals (Sweden)

    Carlos Ramon Silveira Mendes

    2013-10-01

    Full Text Available Transanal endoscopic microsurgery is a minimally-invasive approach for rectal lesions. Superior exposure and access to the entire rectum result in lesser risk of compromised margins and lower recurrence rates, when compared to conventional transanal excision. The aim of this study was to describe a single institution's initial experience with transanal minimally invasive surgery (TAMIS. This was a prospective review of our database. Elev- en procedures from January 2012 to June 2013 were analyzed. Results: eleven operations were completed. Five men were evaluated. Mean age was 62.9 (40-86. Mean follow-up was 9.3 (2-17 months. Average tumor size was 3.8 (1.8-8 cm. Mean distance from anal verge was 6.3 (3-12 cm. Mean operating time was 53.73 (28-118 min. Postoperative complica- tion rate was 9.1%. There were no readmissions. Mortality was null. Operative pathology disclosed the presence of adenoma in four patients, invasive adenocarcinoma in two, neu- roendocrine carcinoma in three, and no residual lesion in one case. TAMIS is a minimally- invasive procedure with low postoperative morbidity at the initial experience. TAMIS is a curative procedure for benign lesions and for selected early cancers. It is useful after neoadjuvant therapy for strictly selected cancers, pending the results of multi-institutional trials. Resumo: Microcirurgia endoscópica transanal é uma abordagem minimamente invasiva para lesões retais. Apresenta menor risco de margem comprometida e menores taxas de recorrência em comparação com excisão transanal convencional. Objetivou-se descrever a experiência inicial, de uma única instituição, com cirurgia minimamente invasiva transanal (TAMIS. Avaliação prospectiva de nosso banco de dados. Onze procedimentos de janeiro de 2012 a junho de 2013, foram analisados. Resultados: onze operações foram concluídas. Havia cinco homens. A média de idade foi de 62,9 (40-86. O acompanhamento médio foi de ww9,3 (2-17 meses. O

  3. Initial reconstruction results from a simulated adaptive small animal C shaped PET/MR insert

    Energy Technology Data Exchange (ETDEWEB)

    Efthimiou, Nikos [Technological Educational Institute of Athens (Greece); Kostou, Theodora; Papadimitroulas, Panagiotis [Technological Educational Institute of Athens (Greece); Department of Medical Physics, School of Medicine, University of Patras (Greece); Charalampos, Tsoumpas [Division of Biomedical Imaging, University of Leeds, Leeds (United Kingdom); Loudos, George [Technological Educational Institute of Athens (Greece)

    2015-05-18

    Traditionally, most clinical and preclinical PET scanners, rely on full cylindrical geometry for whole body as well as dedicated organ scans, which is not optimized with regards to sensitivity and resolution. Several groups proposed the construction of dedicated PET inserts for MR scanners, rather than the construction of new integrated PET/MR scanners. The space inside an MR scanner is a limiting factor which can be reduced further with the use of extra coils, and render the use of non-flexible cylindrical PET scanners difficult if not impossible. The incorporation of small SiPM arrays, can provide the means to design adaptive PET scanners to fit in tight locations, which, makes imaging possible and improve the sensitivity, due to the closer approximation to the organ of interest. In order to assess the performance of such a device we simulated the geometry of a C shaped PET, using GATE. The design of the C-PET was based on a realistic SiPM-BGO scenario. In order reconstruct the simulated data, with STIR, we had to calculate system probability matrix which corresponds to this non standard geometry. For this purpose we developed an efficient multi threaded ray tracing technique to calculate the line integral paths in voxel arrays. One of the major features is the ability to automatically adjust the size of FOV according to the geometry of the detectors. The initial results showed that the sensitivity improved as the angle between the detector arrays increases, thus better angular sampling the scanner's field of view (FOV). The more complete angular coverage helped in improving the shape of the source in the reconstructed images, as well. Furthermore, by adapting the FOV to the closer to the size of the source, the sensitivity per voxel is improved.

  4. The Far Ultraviolet M-dwarf Evolution Survey (FUMES): Overview and Initial Results

    Science.gov (United States)

    Pineda, J. Sebastian; France, Kevin; Youngblood, Allison

    2018-01-01

    M-dwarf stars are prime targets for exoplanet searches because of their close proximity and favorable properties for both planet detection and characterization, with current searches around these targets having already discovered several Earth-sized planets within their star’s habitable zones. However, the atmospheric characterization and potential habitability of these exoplanetary systems depends critically on the high-energy stellar radiation environment from X-rays to NUV. Strong radiation at these energies can lead to atmospheric mass loss and is a strong driver of photochemistry in planetary atmospheres. Recently, the MUSCLES Treasury Survey provided the first comprehensive assessment of the high-energy radiation field around old, planet hosting M-dwarfs. However, the habitability and potential for such exoplanetary atmospheres to develop life also depends on the evolution of the atmosphere and hence the evolution of the incident radiation field. The strong high-energy spectrum of young M-dwarfs can have devastating consequences for the potential habitability of a given system. We, thus, introduce the Far Ultraviolet M-dwarf Evolution Survey (FUMES), a new HST-STIS observing campaign targeting 10 early-mid M dwarfs with known rotation periods, including 6 targets with known ages, to assess the evolution of the FUV radiation, including Lyα, of M-dwarf stars with stellar rotation period. We present the initial results of our survey characterizing the FUV emission features of our targets and the implications of our measurements for the evolution of the entire high-energy radiation environment around M-dwarfs from youth to old age.

  5. The SAGES Legacy Unifying Globulars and Galaxies survey (SLUGGS): sample definition, methods, and initial results

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, Jean P.; Romanowsky, Aaron J.; Jennings, Zachary G.; Pota, Vincenzo; Kader, Justin; Roediger, Joel C.; Villaume, Alexa; Arnold, Jacob A.; Woodley, Kristin A. [University of California Observatories, 1156 High Street, Santa Cruz, CA 95064 (United States); Strader, Jay [Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Forbes, Duncan A.; Pastorello, Nicola; Usher, Christopher; Blom, Christina; Kartha, Sreeja S. [Centre for Astrophysics and Supercomputing, Swinburne University, Hawthorn, VIC 3122 (Australia); Foster, Caroline; Spitler, Lee R., E-mail: jbrodie@ucsc.edu [Australian Astronomical Observatory, P.O. Box 915, North Ryde, NSW 1670 (Australia)

    2014-11-20

    We introduce and provide the scientific motivation for a wide-field photometric and spectroscopic chemodynamical survey of nearby early-type galaxies (ETGs) and their globular cluster (GC) systems. The SAGES Legacy Unifying Globulars and GalaxieS (SLUGGS) survey is being carried out primarily with Subaru/Suprime-Cam and Keck/DEIMOS. The former provides deep gri imaging over a 900 arcmin{sup 2} field-of-view to characterize GC and host galaxy colors and spatial distributions, and to identify spectroscopic targets. The NIR Ca II triplet provides GC line-of-sight velocities and metallicities out to typically ∼8 R {sub e}, and to ∼15 R {sub e} in some cases. New techniques to extract integrated stellar kinematics and metallicities to large radii (∼2-3 R {sub e}) are used in concert with GC data to create two-dimensional (2D) velocity and metallicity maps for comparison with simulations of galaxy formation. The advantages of SLUGGS compared with other, complementary, 2D-chemodynamical surveys are its superior velocity resolution, radial extent, and multiple halo tracers. We describe the sample of 25 nearby ETGs, the selection criteria for galaxies and GCs, the observing strategies, the data reduction techniques, and modeling methods. The survey observations are nearly complete and more than 30 papers have so far been published using SLUGGS data. Here we summarize some initial results, including signatures of two-phase galaxy assembly, evidence for GC metallicity bimodality, and a novel framework for the formation of extended star clusters and ultracompact dwarfs. An integrated overview of current chemodynamical constraints on GC systems points to separate, in situ formation modes at high redshifts for metal-poor and metal-rich GCs.

  6. Tangible Results and Progress in Flood Risks Management with the PACTES Initiative

    Science.gov (United States)

    Costes, Murielle; Abadie, Jean-Paul; Ducuing, Jean-Louis; Denier, Jean-Paul; Stéphane

    The PACTES project (Prévention et Anticipation des Crues au moyen des Techniques Spatiales), initiated by CNES and the French Ministry of Research, aims at improving flood risk management, over the following three main phases : - Prevention : support and facilitate the analysis of flood risks and socio-economic impacts (risk - Forecasting and alert : improve the capability to predict and anticipate the flooding event - Crisis management : allow better situation awareness, communication and sharing of In order to achieve its ambitious objectives, PACTES: - integrates state-of-the-art techniques and systems (integration of the overall processing chains, - takes advantage of integrating recent model developments in wheather forecasting, rainfall, In this approach, space technology is thus used in three main ways : - radar and optical earth observation data are used to produce Digital Elevation Maps, land use - earth observation data are also an input to wheather forecasting, together with ground sensors; - satellite-based telecommunication and mobile positioning. Started in December 2000, the approach taken in PACTES is to work closely with users such as civil security and civil protection organisms, fire fighter brigades and city councils for requirements gathering and during the validation phase. It has lead to the development and experimentation of an integrated pre-operational demonstrator, delivered to different types of operational users. Experimentation has taken place in three watersheds representative of different types of floods (flash and plain floods). After a breaf reminder of what the PACTES project organization and aims are, the PACTES integrated pre-operational demonstrator is presented. The main scientific inputs to flood risk management are summarized. Validation studies for the three watersheds covered by PACTES (Moselle, Hérault and Thoré) are detailed. Feedback on the PACTES tangible results on flood risk management from an user point of view

  7. Initial results from the StratoClim aircraft campaign in the Asian Monsoon in summer 2017

    Science.gov (United States)

    Rex, M.

    2017-12-01

    The Asian Monsoon System is one of the Earth's largest and most energetic weather systems. Monsoon rainfall is critical to feeding over a billion people in Asia and the monsoon circulation affects weather patterns over the entire northern hemisphere. The Monsoon also acts like an enormous elevator, pumping vast amounts of air and pollutants from the surface up to the tropopause region at levels above 16km altitude, from where air can ascend into the stratosphere, where it spreads globally. Thus the monsoon affects the chemical composition of the global tropopause region and the stratosphere, and hence plays a key role for the composition of the UTS. Dynamically the monsoon circulation leads to the formation of a large anticyclone at tropopause levels above South Asia - the Asian Monsoon Anticyclone (AMA). Satellite images show a large cloud of aerosols directly above the monsoon, the Asian Tropopause Aerosol Layer (ATAL). In July to August 2017 the international research project StratoClim carried out the first in-situ aircraft measurements in the AMA and the ATAL with the high altitude research aircraft M55-Geophysica. Around 8 scientific flights took place in the airspaces of Nepal, India and Bangladesh and have horizontally and vertically probed the AMA and have well characterized the ATAL along flight patterns that have been carefully designed by a theory, modelling and satellite data analysing team in the field. The aircraft campaign has been complemented by launches of research balloons from ground stations in Nepal, Bangladesh, China and Palau. The presentation will give an overview of the StratoClim project, the aircraft and balloon activities and initial results from the StratoClim Asian Monsoon campaign in summer 2017.

  8. Initial Results from CASSIOPE/ePOP Satellite Overpasses above HAARP in 2014

    Science.gov (United States)

    Siefring, C. L.; Bernhardt, P. A.; Briczinski, S. J., Jr.; James, H. G.; Yau, A. W.; Knudsen, D. J.

    2015-12-01

    The High Frequency Active Auroral Research Program (HAARP) facility was operated in conjunction with overpasses of the enhanced Polar Outflow Probe (ePOP) instruments on the Canadian CASSIOPE satellite. During these overpasses HAARP was operated in several different heating modes and regimes as diagnosed by the characteristics of Stimulated Electromagnetic Emissions (SEE) using ground-based receivers while simultaneously ePOP monitored in-situ HF and VLF signals, looked for ion and electron heating, and provided VHF and UHF signals for propagation effects studies. The e-POP suite of instruments and particularly the ePOP Radio Receiver Instrument (RRI) offer a unique combination diagnostics appropriate for studying the non-linear plasma effects generated high-power HF waves in the ionosphere. In this presentation, the initial results from ePOP observations from two separate 2014 measurement campaigns at HAARP (April 16 to April 29 and May 25 to June 9) will be discussed. Several innovative experiments were performed during the campaign. Experiments explored a wide range of ionospheric effects. These include: 1) Penetration of HF pump waves into the ionosphere via large and small scale irregularities, 2) effects of gyro-harmonic heating and artificial ionization layers, 3) effects of HAARP beam shape with O- and X-mode transmissions, 4) coupling of Lower Hybrid modes into Whistler waves, 5) D/E-region VLF generation in the ionosphere using VLF modulation of the HF pump 6) scattering of VHF and UHF signals and 7) scattering and non-linear modulation of a 9.5 MHz probe wave propagating through the region of the ionosphere modified by HAARP. This work supported by the Naval Research Laboratory Base Program.

  9. Initial 2-year results of CardioCel® patch implantation in children.

    Science.gov (United States)

    Pavy, Carine; Michielon, Guido; Robertus, Jan Lukas; Lacour-Gayet, François; Ghez, Olivier

    2018-03-01

    We present the initial 2-year results of CardioCel® patch (Admedus Regen Pty Ltd, Perth, WA, Australia) implantation in paediatric patients with congenital heart diseases. This was a single-centre retrospective study with prospectively collected data of all patients aged 18 years and under operated for congenital heart disease. The patch was introduced in 2014, with clinical practice committee approval and a special consent in case of an Ozaki procedure. Standard follow-up was performed with systematic clinical exams and echocardiograms. In case of reoperation or graft failure, the patch was removed and sent for a histological examination. Between March 2014 and April 2016, 101 patients had surgical repair using a CardioCel patch. The mean age was 22 (±36.3) months, and the mean weight was 9.7 (±10.3) kg. No infections and no intraoperative implantation difficulties were associated with the patch. The median follow-up period was 212 (range 4-726) days. The overall 30-day postoperative mortality was 3.8% (n = 4), none of which were related to graft failure. Five children were reoperated because of graft failure, 4 of whom had the patch implanted for aortic and were aged less than 10 days. The indications for patch implantation in the aortic position were aortopulmonary window, truncus arteriosus, coarctation and aortic arch hypoplasia repair. The median time between the first and the second operation for graft failure was 245 (range 5-480) days. Our experience shows that the patch is well tolerated in the septal, valvar and pulmonary artery positions. However, we experienced graft failures in infants in the aortic position. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  10. Initial reconstruction results from a simulated adaptive small animal C shaped PET/MR insert

    International Nuclear Information System (INIS)

    Efthimiou, Nikos; Kostou, Theodora; Papadimitroulas, Panagiotis; Charalampos, Tsoumpas; Loudos, George

    2015-01-01

    Traditionally, most clinical and preclinical PET scanners, rely on full cylindrical geometry for whole body as well as dedicated organ scans, which is not optimized with regards to sensitivity and resolution. Several groups proposed the construction of dedicated PET inserts for MR scanners, rather than the construction of new integrated PET/MR scanners. The space inside an MR scanner is a limiting factor which can be reduced further with the use of extra coils, and render the use of non-flexible cylindrical PET scanners difficult if not impossible. The incorporation of small SiPM arrays, can provide the means to design adaptive PET scanners to fit in tight locations, which, makes imaging possible and improve the sensitivity, due to the closer approximation to the organ of interest. In order to assess the performance of such a device we simulated the geometry of a C shaped PET, using GATE. The design of the C-PET was based on a realistic SiPM-BGO scenario. In order reconstruct the simulated data, with STIR, we had to calculate system probability matrix which corresponds to this non standard geometry. For this purpose we developed an efficient multi threaded ray tracing technique to calculate the line integral paths in voxel arrays. One of the major features is the ability to automatically adjust the size of FOV according to the geometry of the detectors. The initial results showed that the sensitivity improved as the angle between the detector arrays increases, thus better angular sampling the scanner's field of view (FOV). The more complete angular coverage helped in improving the shape of the source in the reconstructed images, as well. Furthermore, by adapting the FOV to the closer to the size of the source, the sensitivity per voxel is improved.

  11. Initial results of the oesophageal and gastric cancer registry from the Comunidad Valenciana.

    Science.gov (United States)

    Escrig, Javier; Mingol, Fernando; Martí, Roberto; Puche, José; Trullenque, Ramón; Barreras, José Antonio; Asencio, Francisco; Aguiló, Javier; Navarro, José Manuel; Alberich, Carmen; Salas, Dolores; Lacueva, Francisco Javier

    2017-10-01

    To evaluate the initial results of the oesophagogastric cancer registry developed for the Sociedad Valenciana de Cirugía and the Health Department of the Comunidad Valenciana (Spain). Fourteen of the 24 public hospitals belonging to the Comunidad Valenciana participated. All patients with diagnosis of oesophageal or gastric carcinomas operated from January 2013 to December 2014 were evaluated. Demographic, clinical and pathological data were analysed. Four hundred and thirty-four patients (120 oesophageal carcinomas and 314 gastric carcinomas) were included. Only two hospitals operated more than 10 patients with oesophageal cancer per year. Transthoracic oesophaguectomy was the most frequent approach (84.2%) in tumours localized within the oesophagus. A total gastrectomy was performed in 50.9% patients with gastroesophageal junction (GOJ) carcinomas. Postoperative 30-day and 90-day mortality were 8% and 11.6% in oesophageal carcinoma and 5.9 and 8.6% in gastric carcinoma. Before surgery, middle oesophagus carcinomas were treated mostly (76,5%) with chemoradiotherapy. On the contrary, lower oesophagus and GOJ carcinomas were treated preferably with chemotherapy alone (45.5 and 53.4%). Any neoadjuvant treatment was administered to 73.6% of gastric cancer patients. Half patients with oesophageal carcinoma or gastric carcinoma received no adjuvant treatment. This registry revealed that half patients with oesophageal cancer were operated in hospitals with less than 10 cases per year at the Comunidad Valenciana. Also, it detected capacity improvement for some clinical outcomes of oesophageal and gastric carcinomas. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

    Science.gov (United States)

    Viollet, Coralie; Davis, David A.; Tekeste, Shewit S.; Reczko, Martin; Pezzella, Francesco; Ragoussis, Jiannis

    2017-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases. PMID:28046107

  13. [Effects of exogenous spermidine on Cucumis sativus L. seedlings photosynthesis under root zone hypoxia stress].

    Science.gov (United States)

    Wang, Tian; Wang, Suping; Guo, Shirong; Sun, Yanjun

    2006-09-01

    With water culture, this paper studied the effects of exogenous spermidine (Spd) on the net photosynthetic rate (Pn), intercellular CO2 concentrations (Ci), stomatal conductance (Gs), transpiration rate (Tr), apparent quantum yield (phi c), and carboxylation efficiency (CE) of cucumber seedlings tinder hypoxia stress. The results showed that the Pn decreased gradually under hypoxia stress, and reached the minimum 10 days after by 63. 33% of the control. Compared with that of hypoxia-stressed plants, the Pn after 10 days application of exogenous Spd increased 1.25 times. A negative correlation (R2 = 0.4730 - 0.7118) was found between Pn and Ci. Gs and Tr changed in wider ranges, which decreased under hypoxia-stress, but increased under hypoxia-stress plus exogenous Spd application. There was a significant positive correlation between Gs and Tr (R2 = 0.7821 - 0.9458), but these two parameters had no significant correlation with Pn; Hypoxia stress induced a decrease of phi c and CE by 63.01% and 72.33%, respectively, while hypoxia stress plus exogenous Spd application made phi c and CE increase by 23% and 14%, respectively. The photo-inhibition of cucumber seedlings under hypoxia stress was mainly caused by non-stomatal limitation, while exogenous Spd alleviated the hypoxia stress by repairing photosynthesis system.

  14. Low-cost autonomous orbit control about Mars: Initial simulation results

    Science.gov (United States)

    Dawson, S. D.; Early, L. W.; Potterveld, C. W.; Königsmann, H. J.

    1999-11-01

    Interest in studying the possibility of extraterrestrial life has led to the re-emergence of the Red Planet as a major target of planetary exploration. Currently proposed missions in the post-2000 period are routinely calling for rendezvous with ascent craft, long-term orbiting of, and sample-return from Mars. Such missions would benefit greatly from autonomous orbit control as a means to reduce operations costs and enable contact with Mars ground stations out of view of the Earth. This paper present results from initial simulations of autonomously controlled orbits around Mars, and points out possible uses of the technology and areas of routine Mars operations where such cost-conscious and robust autonomy could prove most effective. These simulations have validated the approach and control philosophies used in the development of this autonomous orbit controller. Future work will refine the controller, accounting for systematic and random errors in the navigation of the spacecraft from the sensor suite, and will produce prototype flight code for inclusion on future missions. A modified version of Microcosm's commercially available High Precision Orbit Propagator (HPOP) was used in the preparation of these results due to its high accuracy and speed of operation. Control laws were developed to allow an autonomously controlled spacecraft to continuously control to a pre-defined orbit about Mars with near-optimal propellant usage. The control laws were implemented as an adjunct to HPOP. The GSFC-produced 50 × 50 field model of the Martian gravitational potential was used in all simulations. The Martian atmospheric drag was modeled using an exponentially decaying atmosphere based on data from the Mars-GRAM NASA Ames model. It is hoped that the simple atmosphere model that was implemented can be significantly improved in the future so as to approach the fidelity of the Mars-GRAM model in its predictions of atmospheric density at orbital altitudes. Such additional work

  15. Initial Results from the Micro-pulse Lidar Network (MPL-Net)

    Science.gov (United States)

    Welton, Ellsworth J.; Campbell, James R.; Berkoff, Timothy A.; Spinhirne, James D.; Ginoux, Paul; Starr, David OC. (Technical Monitor)

    2001-01-01

    The micro-pulse lidar system (MPL) was developed in the early 1990s and was the first small, eye-safe, and autonomous lidar built for full time monitoring of cloud and aerosol vertical distributions. In 2000, a new project using MPL systems was started at NASA Goddard Space Flight Center. This new project, the Micro-pulse Lidar Network or MPL-Net, was created to provide long-term observations of aerosol and cloud vertical profiles at key sites around the world. This is accomplished using both NASA operated sites and partnerships with other organizations owning MPL systems. The MPL-Net sites are co-located with NASA AERONET sunphotometers to provide aerosol optical depth data needed for calibration of the MPL. In addition to the long-term sites, MPL-Net provides lidar support for a limited number of field experiments and ocean cruises each year. We will present an overview of the MPL-Net project and show initial results from the first two MPL-Net sites at the South Pole and at Goddard Space Flight Center. Observations of dust layers transported from the Gobi desert, across the Pacific Ocean, to the east coast of the United States will also be shown. MPL-Net affiliated instruments were in place at the desert source region in China, on a research vessel in the Sea of Japan, at ARM sites in Alaska and Oklahoma, and finally at our home site in Maryland (GSFC) during the massive dust storms that occurred in April 2001. The MPL observations of dust layers at each location are shown in comparison to dust layers predicted using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport model (GOCART). Finally, the MPL-Net project is the primary ground-validation program for the Geo-Science Laser Altimeter System (GLAS) satellite lidar project (launch date 2002). We will present an overview demonstrating how MPL-Net results are used to help prepare the GLAS data processing algorithms and assist in the calibration/validation of the GLAS data products.

  16. Exploratory X-ray monitoring of luminous radio-quiet quasars at high redshift: Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Shemmer, Ohad; Stein, Matthew S. [Department of Physics, University of North Texas, Denton, TX 76203 (United States); Brandt, W. N.; Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Paolillo, Maurizio [Dipartimento di Scienze Fisiche, Università Federico II di Napoli, via Cinthia 6, I-80126 Napoli (Italy); Kaspi, Shai [School of Physics and Astronomy and the Wise Observatory, Tel Aviv University, Tel Aviv 69978 (Israel); Vignali, Cristian [Dipartimento di Astronomia, Università degli studi di Bologna, via Ranzani 1, I-40127 Bologna (Italy); Lira, Paulina [Departamento de Astronomia, Universidad de Chile, Camino del Observatorio 1515, Santiago (Chile); Gibson, Robert R., E-mail: ohad@unt.edu [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States)

    2014-03-10

    We present initial results from an exploratory X-ray monitoring project of two groups of comparably luminous radio-quiet quasars (RQQs). The first consists of four sources at 4.10 ≤ z ≤ 4.35, monitored by Chandra, and the second is a comparison sample of three sources at 1.33 ≤ z ≤ 2.74, monitored by Swift. Together with archival X-ray data, the total rest-frame temporal baseline spans ∼2-4 yr and ∼5-13 yr for the first and second group, respectively. Six of these sources show significant X-ray variability over rest-frame timescales of ∼10{sup 2}-10{sup 3} days; three of these also show significant X-ray variability on rest-frame timescales of ∼1-10 days. The X-ray variability properties of our variable sources are similar to those exhibited by nearby and far less luminous active galactic nuclei (AGNs). While we do not directly detect a trend of increasing X-ray variability with redshift, we do confirm previous reports of luminous AGNs exhibiting X-ray variability above that expected from their luminosities, based on simplistic extrapolation from lower luminosity sources. This result may be attributed to luminous sources at the highest redshifts having relatively high accretion rates. Complementary UV-optical monitoring of our sources shows that variations in their optical-X-ray spectral energy distribution are dominated by the X-ray variations. We confirm previous reports of X-ray spectral variations in one of our sources, HS 1700+6416, but do not detect such variations in any of our other sources in spite of X-ray flux variations of up to a factor of ∼4. This project is designed to provide a basic assessment of the X-ray variability properties of RQQs at the highest accessible redshifts that will serve as a benchmark for more systematic monitoring of such sources with future X-ray missions.

  17. [Evaluation of initial results of treatment of lead poisoning with EDTA].

    Science.gov (United States)

    Petkova, V; Adjarov, D; Pavlova, S; Naydenova, E; Kerimova, M; Kuneva, T

    1994-01-01

    The results of EDTA therapy were studied in 37 workers of a battery factory consisting of males with varying degrees of occupational lead poisoning (low exposure: 10 subjects, blood lead levels (PbB) lower than 400 micrograms/l with slight alterations in heme biosynthesis; beyond limit of effect: 5 subjects, PbB > 400 micrograms/l; slight intoxication: 19 subjects, with marked alterations in heme synthesis and preclinical signs of intoxication; average degree of intoxication: 3 subjects with clinical signs of intoxication. Clinical symptoms and the following parameters were investigated: blood lead (PbB), delta-aminolevulinic acid dehydratase in erythrocytes (ALA-D), zinc protoporphyrin (PP) in erythrocytes and delta-aminolevulinic acid (ALA) in 24-hour urine before and after EDTA chelating therapy. Simultaneous measurement of ALA-D and PP showed high diagnostic sensitivity in detecting lead poisoning in occupationally exposed subjects. In view of the high interindividual variability of the results, these indices did not, however, permit a useful differentiation to be made of the different degrees of intoxication at individual level, even though a good correlation was observed between PbB and porphyrin metabolism indices. From the alterations observed in ALA-D and PP values it was not possible to establish an association between degree of alteration and types of clinical symptoms in the different intoxication studies. At the end of EDTA treatment, a clinical improvement was observed in all cases studied but only in 5 cases was a reduction in PbB observed, to levels below 1.20 mol/l, which is accepted as a permissible limit for the general population; in 17 cases PbB remained at levels above the critical value for occupational lead poisoning (400 micrograms/l), although there was a decrease after treatment. The improvement observed in the indices of porphyrin metabolism at the end of treatment was only slight: significant variations were measured only for PbB. After

  18. Initial Results From The Micro-pulse Lidar Network (MPL-Net)

    Science.gov (United States)

    Welton, E. J.; Campbell, J. R.; Berkoff, T. A.; Spinhirne, J. D.; Ginoux, P.

    2001-12-01

    The micro-pulse lidar system (MPL) was developed in the early 1990s and was the first small, eye-safe, and autonomous lidar built for fulltime monitoring of cloud and aerosol vertical distributions. In 2000, a new project using MPL systems was started at NASA Goddard Space Flight Center. This new project, the Micro-pulse Lidar Network or MPL-Net, was created to provide long-term observations of aerosol and cloud vertical profiles at key sites around the world. This is accomplished using both NASA operated sites and partnerships with other organizations owning MPL systems. The MPL-Net sites are co-located with NASA AERONET sunphotometers to provide aerosol optical depth data needed for calibration of the MPL. In addition to the long-term sites, MPL-Net provides lidar support for a limited number of field experiments and ocean cruises each year. We will present an overview of the MPL-Net project and show initial results from the first two MPL-Net sites at the South Pole and at Goddard Space Flight Center. Observations of dust layers transported from the desert regions of China, across the Pacific Ocean, to the east coast of the United States will also be shown. MPL-Net affiliated instruments were in place at the desert source region in China, on a research vessel in the Sea of Japan, at ARM sites in Alaska and Oklahoma, and finally at our home site in Maryland (GSFC) during the massive dust storms that occurred in April 2001. The MPL observations of dust layers at each location are shown in comparison to dust layers predicted using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport model (GOCART). Finally, the MPL-Net project is the primary ground-validation program for the Geo-Science Laser Altimeter System (GLAS) satellite lidar project (launch date 2002). We will present an overview demonstrating how MPL-Net results are used to help prepare the GLAS data processing algorithms and assist in the calibration/validation of the GLAS data

  19. Physiological determinants of human acute hypoxia tolerance.

    Science.gov (United States)

    2013-11-01

    AbstractIntroduction. We investigated possible physiological determinants of variability in hypoxia tolerance in subjects given a 5-minute normobaric exposure to 25,000 ft equivalent. Physiological tolerance to hypoxia was defined as the magnitude of...

  20. Tumor hypoxia, p53, and prognosis in cervical cancers

    International Nuclear Information System (INIS)

    Haensgen, Gabriele; Krause, Ulf; Becker, Axel; Stadler, Peter; Lautenschlaeger, Christine; Wohlrab, Wolfgang; Rath, Friedrich W.; Molls, Michael; Dunst, Juergen

    2001-01-01

    Background: The p53 protein is involved in the regulation of initiation of apoptosis. In vitro, p53-deficient cells do not respond to hypoxia with apoptosis as do p53-normal cells, and this may lead to a relative growth advantage of cells without a functioning p53 under hypoxia. On the basis of this hypothesis, a selection of cells with a functionally inactive p53 may occur in hypoxic tumors. The development of uterine cervical carcinomas is closely associated with infections of human papilloma viruses, which may cause a degradation of the tumor suppressor gene p53, resulting in a restriction of apoptosis. Thus, cervical cancers have often a functionally inactive p53. The purpose of our clinical study was therefore to investigate the association between p53, hypoxia, and prognosis in cervical cancers in which the oxygenation status can be determined by clinical methods. Material and Methods: Seventy patients with locally advanced squamous cell cervical cancer Stages IIB (n=14), IIIB (n=49), and IVA (n=7) were investigated in the period from 1996 through 1999. All were treated with definitive radiotherapy with curative intent by a combination of external radiotherapy plus high-dose-rate afterloading. Before therapy, tumor oxygenation was measured with a needle probe polarographically using the Eppendorf histograph. Hypoxic tumors were defined as those with pO 2 measurements below 5 mm Hg (HF5). Pretreatment biopsies were taken and analyzed immunohistologically for p53 protein expression with the DO-7 antibody. The DNA index was measured by flow cytometry. The statistical data analysis was done with SPSS 9.0 for Windows. Results: The 3-year overall survival was 55% for the whole group of patients. Clinical prognostic factors in a multivariate analysis were pretreatment hemoglobin level (3-year survival 62% for patients with a pretreatment hemoglobin ≥11 g/dl vs. 27% for hemoglobin <11 g/dl, p=0.006) and FIGO stage (Stage IIB: 65%; Stage IIIB: 60%; Stage IVA: 29%, p

  1. Initial results with the Berkeley on-line mass separator-RAMA

    International Nuclear Information System (INIS)

    Cerny, J.; Moltz, D.M.; Evans, H.C.; Vieira, D.J.; Parry, R.F.; Wouters, J.M.; Gough, R.A.; Zisman, M.S.

    1977-11-01

    Initial performance is described for a reasonably fast and universal (having little or no chemical selectivity) on-line mass analysis system used to expand capabilities in studying nuclei far from stability. The system is termed RAMA, an acronym for Recoil Atom Mass Analyzer. Basically, this system utilizes the helium-jet method to transport activity to a Sidenius hollow-cathode ion source which is coupled to a mass spectrometer. Initial experiments and planned improvements are discussed. Transport efficiencies of between 10 and 60 percent have routinely been achieved, though the latter is much more typical when conditions are optimized

  2. Overview of results and perspectives from the Shoreham major common-cause initiating events study

    International Nuclear Information System (INIS)

    Joksimovich, V.; Orvis, D.D.; Paccione, R.J.

    1986-01-01

    This study represents the continuation of a large effort by LILCO to fully understand the potential hazards posed by future operation of the Shoreham Nuclear Power Stations (SNPS). The Shoreham Probabilistic Risk Assessment, a level 3 PRA without external events, provided a characterization of the accident sequences that could leave the core in a condition in which it would be vulnerable to severe damage if further mitigating actions were not taken. It estimated the frequency and magnitude of the potential radioactivity releases associated with such sequences. The study was limited to accident sequences initiated by so called internal events to the plant including a loss of offsite power. It also characterized the public risk associated with those accident sequences. The ''Major Common-Cause Initiating Events Study'' (MCCI) for the Shoreham plant was performed to obtain insights into the plant's susceptibility to, and inherent defenses against, certain MCCIs. Major common-cause initiating events are occurrences which have the potential to initiate a plant transient or LOCA and, also, damage one or more plant systems needed to mitigate the effects of a transient or LOCA. The scope of the MCCI study included detailed analyses of seismic events and fires through the severe core damage and bounding analyses of aircraft crashes, windstorms, turbine missiles and release of hazardous materials near the plant

  3. Fast pyrolysis in a novel wire-mesh reactor: design and initial results

    NARCIS (Netherlands)

    Hoekstra, E.; van Swaaij, Willibrordus Petrus Maria; Kersten, Sascha R.A.; Hogendoorn, Kees

    2012-01-01

    Pyrolysis is known to occur by decomposition processes followed by vapour phase reactions. The goal of this research is to develop a novel device to study the initial decomposition processes. For this, a novel wire-mesh reactor was constructed. A small sample (<0.1 g) was clamped between two meshes

  4. The magnetic field investigation on the ARASE (ERG) mission: Data characteristics and initial scientific results

    Science.gov (United States)

    Matsuoka, A.; Teramoto, M.; Nomura, R.; Nose, M.; Fujimoto, A.; Tanaka, Y.; Shinohara, M.; Nagatsuma, T.; Shiokawa, K.; Obana, Y.; Miyoshi, Y.; Takashima, T.; Shinohara, I.

    2017-12-01

    The ARASE (ERG) satellite was successfully launched on December 20 2016. A fluxgate magnetometer (MGF) was built for the ARASE satellite to measure DC and low-frequency magnetic field. The requirements to the magnetic field measurements by ARASE was defined as (1) accuracy of the absolute field intensity is within 5 nT (2) angular accuracy of the field direction is within 1 degree (3) measurement frequency range is from DC to 60Hz or wider. MGF measures the vector magnetic field with the original sampling frequency of 256 Hz. The dynamic range is switched between +/-8000nT and +/- 60000nT according to the background field intensity. The MGF initial checkout was carried on January 10th 2017, when the MGF normal performance and downlinked data were confirmed. The 5-m length MAST for the sensor was deployed on 17th January. The nominal operation of MGF started in March 2017. The MGF data are calibrated based on the results from the ground experiments and in-orbit data analysis. The MGF CDF files are distributed by the ARASE Science Center and available by Space Physics Environment Data Analysis Software (SPEDAS). The acceleration process of the charged particles in the inner magnetosphere is considered to be closely related to the deformation and perturbation of the magnetic field. Accurate measurement of the magnetic field is required to understand the acceleration mechanism of the charged particles, which is one of the major scientific objectives of the ARASE mission. We designed a fluxgate magnetometer which is optimized to investigate following topics; (1) accurate measurement of the background magnetic field - the deformation of the magnetic field and its relationship with the particle acceleration. (2) MHD waves - measurement of the ULF electromagnetic waves of frequencies about 1mHz (Pc4-5), and investigation of the radiation-belt electrons radially diffused by the resonance with the ULF waves. (3) EMIC waves - measurement of the electromagnetic ion

  5. Initial Results from the Vector Electric Field Investigation on the C/NOFS Satellite

    Science.gov (United States)

    Pfaff, R.; Rowland, D.; Acuna, M.; Le, G.; Farrell, W.; Holzworth, R.; Wilson, G.; Burke, W.; Freudenreich, H.; Bromund, K.; hide

    2009-01-01

    Initial results are presented from the Vector Electric Field Investigation (VEFI) on the Air Force Communication/Navigation Outage Forecasting System (C/NOFS) satellite, a mission designed to understand, model, and forecast the presence of equatorial ionospheric irregularities. The VEFI instrument includes a vector DC electric field detector, a fixed-bias Langmuir probe operating in the ion saturation regime, a flux gate magnetometer, an optical lightning detector, and associated electronics including a burst memory. The DC electric field detector has revealed zonal and meridional electric fields that undergo a diurnal variation, typically displaying eastward and outward-directed fields during the day and westward and downward-directed fields at night. In general, the measured DC electric field amplitudes are in the 0.5-2 mV/m range, corresponding to I3 x B drifts of the order of 30-150 m/s. What is surprising is the high degree of large-scale (10's to 100's of km) structure in the DC electric field, particularly at night, regardless of whether well-defined spread-F plasma density depletions are present. The spread-F density depletions and corresponding electric fields that have been detected thus far have displayed a preponderance to appear between midnight and dawn. Associated with the narrow plasma depletions that are detected are broad spectra of electric field and plasma density irregularities for which a full vector set of measurements is available for detailed study. On some occasions, localized regions of low frequency (field broadband irregularities have been detected, suggestive of filamentary currents, although there is no one-to-one correspondence of these waves with the observed plasma density depletions, at least within the data examined thus far. Finally, the data set includes a wide range of ELF/VLF/HF waves corresponding to a variety of plasma waves, in particular banded ELF hiss, whistlers, and lower hybrid wave turbulence triggered by lightning

  6. Overview of the Ozone Water-Land Environmental Transition Study: Summary of Observations and Initial Results

    Science.gov (United States)

    Berkoff, T.; Sullivan, J.; Pippin, M. R.; Gronoff, G.; Knepp, T. N.; Twigg, L.; Schroeder, J.; Carrion, W.; Farris, B.; Kowalewski, M. G.; Nino, L.; Gargulinski, E.; Rodio, L.; Sanchez, P.; Desorae Davis, A. A.; Janz, S. J.; Judd, L.; Pusede, S.; Wolfe, G. M.; Stauffer, R. M.; Munyan, J.; Flynn, J.; Moore, B.; Dreessen, J.; Salkovitz, D.; Stumpf, K.; King, B.; Hanisco, T. F.; Brandt, J.; Blake, D. R.; Abuhassan, N.; Cede, A.; Tzortziou, M.; Demoz, B.; Tsay, S. C.; Swap, R.; Holben, B. N.; Szykman, J.; McGee, T. J.; Neilan, J.; Allen, D.

    2017-12-01

    combination of observations provided a unique 4-D (horizontal, vertical, and time) view of O3 to help provide feedback to air quality forecast models as well as future satellite remote sensing systems such as NASA's TEMPO mission. In this presentation, a summary of observations and initial results will be presented from the OWLETS campaign.

  7. Penn State geoPebble system: Design,Implementation, and Initial Results

    Science.gov (United States)

    Urbina, J. V.; Anandakrishnan, S.; Bilen, S. G.; Fleishman, A.; Burkett, P.

    2014-12-01

    The Penn State geoPebble system is a new network of wirelessly interconnected seismic and GPS sensor nodes with flexible architecture. This network will be used for studies of ice sheets in Antarctica and Greenland, as well as to investigate mountain glaciers. The network will consist of ˜150 geoPebbles that can be deployed in a user-defined spatial geometry. We present our design methodology, which has enabled us to develop these state-of- the art sensors using commercial-off-the-shelf hardware combined with custom-designed hardware and software. Each geoPebble is a self- contained, wirelessly connected sensor for collecting seismic measurements and position information. Key elements of each node encompasses a three-component seismic recorder, which includes an amplifier, filter, and 24- bit analog-to-digital converter that can sample up to 10 kHz. Each unit also includes a microphone channel to record the ground-coupled airwave. The timing for each node is available from GPS measurements and a local precision oscillator that is conditioned by the GPS timing pulses. In addition, we record the carrier-phase measurement of the L1 GPS signal in order to determine location at sub-decimeter accuracy (relative to other geoPebbles within a few kilometers radius). Each geoPebble includes 16 GB of solid-state storage, wireless communications capability to a central supervisory unit, and auxiliary measurements capability (including tilt from accelerometers, absolute orientation from magnetometers and temperature). A novel aspect of the geoPebble is a wireless charging system for the internal battery (using inductive coupling techniques). The geoPebbles include all the sensors (geophones, GPS, microphone), communications (WiFi), and power (battery and charging) internally, so the geoPebble system can operate without any cabling connections (though we do provide an external connector so that different geophones can be used). We report initial field-deployment results and

  8. The path from ITER to a power plant - initial results from the ARIES ''Pathways'' program

    International Nuclear Information System (INIS)

    Najmabadi, F.

    2007-01-01

    The US national power plant studies program, ARIES, has initiated a 3-year integrated study, called the ''Pathways Program'' to investigate what the fusion program needs to do, in addition to successful operation of the ITER, in order to transform fusion into a commercial reality. The US power industry and regulatory agencies view the demonstration power plant, DEMO, as a device which is build and operated by industry, possibly with government participation, to demonstrate the commercial readiness of fusion power. As such, the ''Pathways'' programs will investigate what is needed, in addition to successful operation of ITER, to convince industry to move forward with a fusion DEMO. While many reports exists that provide a strategic view of the needs for fusion development; in the ITER era, a much more detailed view is needed to provide the necessary information for program planning. By comparing the anticipated results from ITER and existing facilities with the requirements for a power plant in the first phase of the Pathways study, we will develop a comprehensive list of remaining R and D items for developing fusion, will identify metrics for distributing resources among R and D issues, and will identify which of those items can/should be done in existing or simulation facilities. In the second phase of the study, we will develop potential embodiments for the fusion test facility (ies) and explore their cost/performance parametrically. An important by-product of this study is the identification of key R and D issues that can be performed and resolved in existing facilities to make the fusion facility cheaper and/or a higher performance device. This paper summarizes the results from the first phase of our study. We have adopted a ''holistic'' or integrated approach with the focus on the needs of the customer. In such an approach, the remaining R and D should generate all of the information needed by industry to move forward with the DEMO, i.e., data needed to

  9. Nutritional status in chronic obstructive pulmonary disease: role of hypoxia.

    Science.gov (United States)

    Raguso, Comasia A; Luthy, Christophe

    2011-02-01

    In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Teleosts in hypoxia : Aspects of anaerobic metabolism

    NARCIS (Netherlands)

    Van den Thillart, G.; van Waarde, Aren

    1985-01-01

    Moderate hypoxia can be tolerated by many fish species, while only some species survive severe hypoxia or anoxia. Hypoxia usually activates anaerobic glycolysis, which may be temporary when the animals are able to improve their oxygen extraction capacity. Switching over to aerobic metabolism allows

  11. Susceptibility to hypoxia and breathing control changes after short-term cold exposures

    Directory of Open Access Journals (Sweden)

    Lyudmila T. Kovtun

    2013-08-01

    Full Text Available Background . Hypoxia is the reduction of oxygen availability due to external or internal causes. There is large individual variability of response to hypoxia. Objective . The aim of this study was to define individual and typological features in susceptibility to hypoxia, its interrelation with hypoxic and hypercapnic ventilatory responses (HVR and HCVR, respectively and their changes after cold acclimation. Design . Twenty-four healthy men were tested. HVR and HCVR were measured by the rebreathing method during hypoxic and hypercapnic tests, respectively. These tests were carried out in thermoneutral conditions before and after cold exposures (nude, at 13°C, 2 h daily, for 10 days. Susceptibility to hypoxia (sSaO2 was determined as haemoglobin saturation slope during hypoxic test. Results . It was found that HVR and HCVR significantly increased and susceptibility to hypoxia (sSaO2 tended to decrease after cold acclimation. According to sSaO2 results before cold exposures, the group was divided into 3: Group 1 – with high susceptibility to hypoxia, Group 2 – medium and Group 3 – low susceptibility. Analysis of variances (MANOVA shows the key role of susceptibility to hypoxia and cold exposures and their interrelation. Posterior analysis (Fisher LSD showed significant difference in susceptibility to hypoxia between the groups prior to cold acclimation, while HVR and HCVR did not differ between the groups. After cold acclimation, susceptibility to hypoxia was not significantly different between the groups, while HCVR significantly increased in Groups 1 and 3, HVR significantly increased in Group 3 and HCVR, HVR did not change in Group 2. Conclusions . Short-term cold exposures caused an increase in functional reserves and improved oxygen supply of tissues in Group 1. Cold exposure hypoxia has caused energy loss in Group 3. Group 2 showed the most appropriate energy conservation reaction mode to cold exposures. No relation was found between

  12. Initial Results of Using Daily CT Localization to Correct Portal Error in Prostate Cancer

    International Nuclear Information System (INIS)

    Lattanzi, Joseph; McNeely, Shawn; Barnes, Scott; Das, Indra; Schultheiss, Timothy E; Hanks, Gerald E.

    1997-01-01

    Purpose: To evaluate the use of daily CT simulation in prostate cancer to correct errors in portal placement and organ motion. Improved localization with this technique should allow the reduction of target margins and facilitate dose escalation in high risk patients while minimizing the risk of normal tissue morbidity. Methods and Materials : Five patients underwent standard CT simulation with the alpha cradle cast, IV contrast, and urethrogram. All were initially treated to 46 Gy in a four field conformal technique which included the prostate, seminal vesicles and pelvic lymph nodes (GTV 1 ). The prostate or prostate and seminal vesicles (GTV 2 ) then received 56 Gy with a 1.0 cm margin to the PTV. At 50 Gy a second CT simulation was performed with IV contrast, urethrogram and the alpha cradle secured to a rigid sliding board. The prostate was contoured, a new isocenter generated, and surface markers placed. Prostate only treatment portals for the final conedown (GTV 3 ) were created with 0.25 cm isodose margins to the PTV. The final six fractions in 2 patients with favorable disease and eight fractions in 3 patients with unfavorable disease were delivered using the daily CT technique. On each treatment day the patient was placed in his cast on the sliding board and a CT scan performed. The daily isocenter was calculated in the A/P and lateral dimension and compared to the 50 Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce perfect portal alignment. To maintain positioning, the patient was transferred to a gurney while on the sliding board in his cast, transported to the treatment room and then transferred to the treatment couch. The patient was then treated to the corrected isocenter. Portal films and real time images were obtained for each portal. Results: Utilizing CT-CT image registration (fusion) of the daily and 50 Gy baseline CT scans the isocenter changes were quantified to reflect the contribution of positional

  13. Preliminary Results from Initial Investigations of Ceres' Cratering Record from Dawn Imaging Data

    Science.gov (United States)

    Schmedemann, Nico; Michael, Gregory; Ivanov, Boris A.; Kneissl, Thomas; Neesemann, Adrian; Hiesinger, Harald; Jaumann, Ralf; Raymond, Carol A.; Russell, Christopher T.

    2015-04-01

    The highly successful Dawn mission [1] finished data collection at Vesta in 2012 and is now on its way to the dwarf planet Ceres. According to the current Ceres approach timeline of the Dawn mission, the ground resolution of the Dawn FC camera [2] will be about 10 times better than Hubble data [3] at the time of the presentation of this work. This may allow for identification of craters about 15 km in diameter. Initial mapping of sample areas may provide enough information of the cratering record in order to compare it with the theoretical Ceres crater production function we present at the 46th LPSC conference (March 16-20, 2015, The Woodlands, Texas) [4]. Our preliminary crater production function for Ceres is derived from the assumption of an icy crust just below a thin surface layer of dust [5], and a projectile population that is very similar to the one that impacted the Moon [6]. In order to scale the lunar cratering record to Ceres we use the Ivanov scaling laws [7], which allow for crater scaling based on parameters that can be derived from observations. The lunar-like approach gave reasonable good results for the crater production function on the asteroids Vesta, Ida, Lutetia and Gaspra [8]. Since the lunar surface is of basaltic composition, the correct scaling between the different materials is challenging. One crucial parameter is the transition diameter from simple to complex craters. Based on the simple to complex transition diameter on Iapetus, an icy satellite of Saturn, we expect this transition at about 12 km crater size at Ceres. This value may be slightly different due to the different temperatures at Ceres and Iapetus. If the simple to complex transition is observed at much larger diameters, the reason could be a substantial fraction of rock in the shallow subsurface of Ceres. In an ice-rich surface material high relaxation rates may also be expected that could change the shape of the crater production function. A thorough geological mapping

  14. Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.

    Science.gov (United States)

    Trimble, Gillian; McStravick, Clodagh; Farling, Peter; Megaw, Katie; McKinstry, Steven; Smyth, Graham; Law, Gillian; Courtney, Heather; Quigley, Gavin; Flannery, Thomas

    2015-01-01

    Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.

  15. Automation and robotics for the Space Exploration Initiative: Results from Project Outreach

    Science.gov (United States)

    Gonzales, D.; Criswell, D.; Heer, E.

    1991-01-01

    A total of 52 submissions were received in the Automation and Robotics (A&R) area during Project Outreach. About half of the submissions (24) contained concepts that were judged to have high utility for the Space Exploration Initiative (SEI) and were analyzed further by the robotics panel. These 24 submissions are analyzed here. Three types of robots were proposed in the high scoring submissions: structured task robots (STRs), teleoperated robots (TORs), and surface exploration robots. Several advanced TOR control interface technologies were proposed in the submissions. Many A&R concepts or potential standards were presented or alluded to by the submitters, but few specific technologies or systems were suggested.

  16. Hypoxia upregulates neutrophil degranulation and potential for tissue injury

    Science.gov (United States)

    Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

    2016-01-01

    Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

  17. Hypoxia-inducible factor signalling mechanisms in the central nervous system.

    Science.gov (United States)

    Corcoran, A; O'Connor, J J

    2013-08-01

    In the CNS, neurones are highly sensitive to the availability of oxygen. In conditions where oxygen availability is decreased, neuronal function can be altered, leading to injury and cell death. Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma and neurodegenerative diseases. Cellular responses to oxygen deprivation are complex and result in activation of short- and long-term mechanisms to conserve energy and protect cells. Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute effects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, pre-synaptic effects of adenosine and other actions at glutamatergic receptors. A more long-term feature of the response of neurones to hypoxia is the activation of transcription factors such as hypoxia-inducible factor. The activation of hypoxia-inducible factor is governed by a family of dioxygenases called hypoxia-inducible factor prolyl 4 hydroxylases (PHDs). Under hypoxic conditions, PHD activity is inhibited, thereby allowing hypoxia-inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia-responsive element sequences of target gene promoters. Inhibition of PHD activity stabilizes hypoxia-inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia-inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of PHD inhibition on synaptic transmission and plasticity in the hippocampus. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  18. Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

    Science.gov (United States)

    Wang, Kang; Smith, Zachary M; Buxton, Richard B; Swenson, Erik R; Dubowitz, David J

    2015-12-15

    Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia. Copyright © 2015 the American Physiological Society.

  19. Plasma volume in acute hypoxia

    DEFF Research Database (Denmark)

    Poulsen, T D; Klausen, T; Richalet, J P

    1998-01-01

    Exposure to acute hypoxia is associated with changes in body fluid homeostasis and plasma volume (PV). This study compared a dye dilution technique using Evans' blue (PV[Evans']) with a carbon monoxide (CO) rebreathing method (PV[CO]) for measurements of PV in ten normal subjects at sea level...

  20. Hepcidin: A Critical Regulator Of Iron Metabolism During Hypoxia

    Science.gov (United States)

    2011-01-01

    inducible factor (HIF)/hypoxia response element ( HRE ) system, as well as recent evidence indicating that localized adipose hypoxia due to obesity may...mechanisms by which hypoxia affects hepcidin expression, to include a review of the hypoxia inducible factor (HIF)/hypoxia response element ( HRE ) system, as...a battery of genes are induced by the hypoxia inducible factor (HIF)/hypoxia response element ( HRE ) system. The HIF system senses O2 levels through

  1. 42 CFR 476.85 - Conclusive effect of QIO initial denial determinations and changes as a result of DRG validations.

    Science.gov (United States)

    2010-10-01

    ... determinations and changes as a result of DRG validations. 476.85 Section 476.85 Public Health CENTERS FOR... denial determinations and changes as a result of DRG validations. A QIO initial denial determination or change as a result of DRG validation is final and binding unless, in accordance with the procedures in...

  2. Obstructive sleep apnea: role of intermittent hypoxia and inflammation.

    Science.gov (United States)

    May, Anna M; Mehra, Reena

    2014-10-01

    Obstructive sleep apnea results in intermittent hypoxia via repetitive upper airway obstruction leading to partial or complete upper airway closure, apneas and hypopneas, respectively. Intermittent hypoxia leads to sympathetic nervous system activation and oxidative stress with a resultant systemic inflammatory cascade. The putative mechanism by which obstructive sleep apnea has been linked to numerous pathologic conditions including stoke, cardiovascular disease, hypertension, and metabolic derangements is through these systemic effects. Treatment of obstructive sleep apnea appears to reduce systemic markers of inflammation and ameliorates the adverse sequelae of this disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. DESTRUCTIVE LESIONS OF BONES AS A RESULT OF MYCOBACTERIAL PROCESS IN CHILDREN WITH INITIAL IMMUNODEFICIENCIES (CLINICAL, DIAGNOSTICAL AND TACTIC PECULIARITIES

    Directory of Open Access Journals (Sweden)

    A.Yu. Mushkin

    2011-01-01

    Full Text Available Initial immunodeficiencies are genetically conditioned defects of immune system; they are the basis for generalized infections including those induced by mycobacteria of tuberculosis complex. The lesions of skeleton in those patients are of different types depending on the kind of immunodeficiency. The article presents the results of clinical observation, conservative and surgical treatment of 12 children with mycobacterial lesions of skeleton on the ground different initial immunodeficiencies — severe combined immune deficiency, chronic granulematosis and insufficiency of interferon and interleukin 12.Key words: children, initial immunodeficiency, mycobacterial infection, bone lesions, surgical treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 60–64

  4. Initial results of high resolution L-H transition studies on DIII-D

    International Nuclear Information System (INIS)

    Wang, G; Rhodes, T L; Doyle, E J; Peebles, W A; Zeng, L; Burrell, K H; McKee, G R; Groebner, R J; Evans, T E

    2004-01-01

    Understanding the L-H transition in tokamaks has been an important area of research for more than two decades. High time resolution diagnostics on DIII-D allow detailed characterization of the L-H transition and, therefore, testing and benchmarking of theoretical models. An experiment was performed in DIII-D utilizing a novel, high temporal and spatial resolution reflectometer density profile system to measure densities from the SOL to the inside separatrix. Initial data analysis indicates different density profile evolution during L-H transitions in upper single-null and lower single-null divertor configuration plasmas. A detailed comparison of the density gradient and fluctuation changes is presented for these two cases

  5. Performance of the Argonne Wakefield Accelerator facility and initial experimental results

    International Nuclear Information System (INIS)

    Gai, W.; Conde, M.; Cox, G.; Konecny, R.; Power, J.; Schoessow, P.; Simpson, J.; Barov, N.

    1996-01-01

    The Argonne Wakefield Accelerator (AWA) facility has begun its experimental program. This unique facility is designed to address advanced acceleration research which requires very short, intense electron bunches. The facility incorporates two photo-cathode based electron sources. One produces up to 100 nC, multi-kiloamp 'drive' bunches which are used to excite wakefields in dielectric loaded structures and in plasma. The second source produces much lower intensity 'witness' pulses which are used to probe the fields produced by the drive. The drive and witness pulses can be precisely timed as well as laterally positioned with respect to each other. We discuss commissioning, initial experiments, and outline plans for a proposed 1 GeV demonstration accelerator. (author)

  6. Performance of the Argonne Wakefield Accelerator Facility and initial experimental results

    International Nuclear Information System (INIS)

    Gai, W.; Conde, M.; Cox, G.; Konecny, R.; Power, J.; Schoessow, P.; Simpson, J.; Barov, N.

    1996-01-01

    The Argonne Wakefield Accelerator facility has begun its experimental program. It is designed to address advanced acceleration research requiring very short, intense electron bunches. It incorporates two photocathode based electron sources. One produces up to 100 nC, multi-kiloamp 'drive' bunches which are used to excite wakefields in dielectric loaded structures and in plasma. The second source produces much lower intensity 'witness' pulses which are used to probe the fields produced by the drive. The drive and witness pulses can be precisely timed as well as laterally positioned with respect to each other. This paper discusses commissioning, initial experiments, and outline plans for a proposed 1 GeV demonstration accelerator

  7. Initial results of high resolution L-H transition studies on DIII-D

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Rhodes, T L [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Doyle, E J [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Peebles, W A [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Zeng, L [Department of Electrical Engineering and PSTI, University of California, Los Angeles, CA 90095 (United States); Burrell, K H [General Atomics, PO Box 85608, San Diego, CA 92186 (United States); McKee, G R [University of Wisconsin-Madison, 1500 Engineering Drive, Madison, WI 53706 (United States); Groebner, R J [General Atomics, PO Box 85608, San Diego, CA 92186 (United States); Evans, T E [General Atomics, PO Box 85608, San Diego, CA 92186 (United States)

    2004-05-01

    Understanding the L-H transition in tokamaks has been an important area of research for more than two decades. High time resolution diagnostics on DIII-D allow detailed characterization of the L-H transition and, therefore, testing and benchmarking of theoretical models. An experiment was performed in DIII-D utilizing a novel, high temporal and spatial resolution reflectometer density profile system to measure densities from the SOL to the inside separatrix. Initial data analysis indicates different density profile evolution during L-H transitions in upper single-null and lower single-null divertor configuration plasmas. A detailed comparison of the density gradient and fluctuation changes is presented for these two cases.

  8. Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

    Science.gov (United States)

    Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

    2004-07-01

    Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

  9. Initial results from the Auto/Oil Air Quality Improvement Research Program

    International Nuclear Information System (INIS)

    McCabe, L.J.

    1993-01-01

    The Auto/Air Quality Improvement Research Program (AQIRP), a cooperative effort by the three major US auto companies and fourteen oil companies, is the most comprehensive research effort ever undertaken to develop data on the air quality effects of the use of various motor fuels in various automotive systems and the relative cost-effectiveness of various fuel/vehicle combinations. Phase 1 of the Program, at a cost of about $15 million, is examining emissions and air quality impacts from current and older vehicles using reformulated gasolines with widely different values of aromatics content, olefin content, oxygenate content and type, sulfur content, vapor pressure (RVP) and 90% distillation temperature. Emissions from Flexible and Variable Fuel vehicles using methanol/gasoline mixtures are also being examined. A second phase with a $25 million budget over three years has also been approved. Initial findings for the Phase 1 study and Phase 2 plans are presented

  10. Initial formulation results for in situ grouting of a waste trench at ORNL Site No. 6

    International Nuclear Information System (INIS)

    Tallent, O.K.; McDaniel, E.W.; Spence, R.D.; Godsey, T.T.

    1987-01-01

    An investigation is being conducted by the Chemical Technology Division to assist the Environmental Sciences Division in developing a grout formulation for use in testing in situ grouting in a waste trench at ORNL Site 6. This final report satisfies the milestone of Subtack 12 entitled, ''Low Level Waste (LLW) Trench Grouting Assessment,'' which was initially issued as RAP-86-7, December 31, 1985. Grouts prepared from dry-solid blends containing Type I Portland cement, ASTM Class C or Class F fly ash, and bentonite, mixed water at ratios of 10 to 15 lb/gal, were evaluated. The grouts prepared with ASTM Class C fly ash exhibited significantly better properties than those prepared with ASTM Class F fly ash. The grouts containing ASTM Class C fly ash satisfy tentative performance criteria for the project. 8 refs., 7 tabs

  11. Initial experimental results from the Laboratory Biosphere closed ecological system facility.

    Science.gov (United States)

    Nelson, M; Dempster, W F; Alling, A; Allen, J P; Rasmussen, R; Silverstone, S; Van Thillo, M

    2003-01-01

    An initial experiment in the Laboratory Biosphere facility, Santa Fe, New Mexico, was conducted May-August 2002 using a soil-based system with light levels (at 12 h per day) of 58-mol m-2 d-1. The crop tested was soybean, cultivar Hoyt, which produced an aboveground biomass of 2510 grams. Dynamics of a number of trace gases showed that methane, nitrous oxide, carbon monoxide, and hydrogen gas had initial increases that were substantially reduced in concentration by the end of the experiment. Methane was reduced from 209 ppm to 11 ppm, and nitrous oxide from 5 ppm to 1.4 ppm in the last 40 days of the closure experiment. Ethylene was at elevated levels compared to ambient during the flowering/fruiting phase of the crop. Soil respiration from the 5.37 m2 (1.46 m3) soil component was estimated at 23.4 ppm h-1 or 1.28 g CO2 h-1 or 5.7 g CO2 m-2 d-1. Phytorespiration peaked near the time of fruiting at about 160 ppm h-1. At the height of plant growth, photosynthesis CO2 draw down was as high as 3950 ppm d-1, and averaged 265 ppm h-1 (whole day averages) during lighted hours with a range of 156-390 ppm h-1. During this period, the chamber required injections of CO2 to continue plant growth. Oxygen levels rose along with the injections of carbon dioxide. Upon several occasions, CO2 was allowed to be drawn down to severely limiting levels, bottoming at around 150 ppm. A strong positive correlation (about 0.05 ppm h-1 ppm-1 with r2 about 0.9 for the range 1000-5000 ppm) was observed between atmospheric CO2 concentration and the rate of fixation up to concentrations of around 8800 ppm CO2. c2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  12. Ten Years of Northern Eurasia Earth Science Partnership Initiative (NEESPI): Results and Future Plans

    Science.gov (United States)

    Groisman, P. Y.; Gutman, G.; Gulev, S.; Maksyutov, S. S.

    2014-12-01

    During recent decades, Northern Eurasia was affected by unprecedented climate and environmental changes. Several droughts and heat waves alternated with hazardous extreme precipitation and flood events. Permafrost thaw, retreating Arctic sea ice, increasing areas of forest fire, and dramatic regional warming buffeted this region, tossing northern Eurasia from one extreme condition to the next. The region stores nearly half of the Earth's terrestrial carbon in permafrost, wetlands, and forested land, so ecosystem changes that release stored carbon could profoundly affect the world's climate. Furthermore, changes to climate and to hydrological and biogeochemical cycles are starting to affect daily life. For example, infrastructure is collapsing as permafrost thaws, severe winter storms increasingly bring businesses to a halt, and a growing water deficit is beginning to strain agricultural production and forestry. To pool resources and facilitate research, the Northern Eurasia Earth Science Partnership Initiative (NEESPI, http://neespi.org) was launched in 2004. With its multidisciplinary focus, the internationally funded NEESPI (more than165 individual international projects during the past decade) has challenged participants to research climate-ecosystem interactions, societal impacts from extreme events in Northern Eurasia, and the feedbacks of these interactions and impacts to the global Earth system. Among the numerous Institutional and private sponsors from the United States, European Union, Russia, China, and Japan, the cornerstone support for the NEESPI studies was provided by the NASA Land Cover and Land Use Change Program and the Russian Academy of Sciences. At this presentation we shall overview the environmental studies conducted by the NEESPI community, brief the audience about the main achievements of the NEESPI researchers, and lay down the plans for the future studies. At the side event of the Meeting, we are going to initiate preparation of the book

  13. Design of an Object-Oriented Turbomachinery Analysis Code: Initial Results

    Science.gov (United States)

    Jones, Scott M.

    2015-01-01

    Performance prediction of turbomachines is a significant part of aircraft propulsion design. In the conceptual design stage, there is an important need to quantify compressor and turbine aerodynamic performance and develop initial geometry parameters at the 2-D level prior to more extensive Computational Fluid Dynamics (CFD) analyses. The Object-oriented Turbomachinery Analysis Code (OTAC) is being developed to perform 2-D meridional flowthrough analysis of turbomachines using an implicit formulation of the governing equations to solve for the conditions at the exit of each blade row. OTAC is designed to perform meanline or streamline calculations; for streamline analyses simple radial equilibrium is used as a governing equation to solve for spanwise property variations. While the goal for OTAC is to allow simulation of physical effects and architectural features unavailable in other existing codes, it must first prove capable of performing calculations for conventional turbomachines. OTAC is being developed using the interpreted language features available in the Numerical Propulsion System Simulation (NPSS) code described by Claus et al (1991). Using the NPSS framework came with several distinct advantages, including access to the pre-existing NPSS thermodynamic property packages and the NPSS Newton-Raphson solver. The remaining objects necessary for OTAC were written in the NPSS framework interpreted language. These new objects form the core of OTAC and are the BladeRow, BladeSegment, TransitionSection, Expander, Reducer, and OTACstart Elements. The BladeRow and BladeSegment consumed the initial bulk of the development effort and required determining the equations applicable to flow through turbomachinery blade rows given specific assumptions about the nature of that flow. Once these objects were completed, OTAC was tested and found to agree with existing solutions from other codes; these tests included various meanline and streamline comparisons of axial

  14. Optical Imaging of Tumor Hypoxia and Evaluation of Efficacy of a Hypoxia-Targeting Drug in Living Animals

    Directory of Open Access Journals (Sweden)

    Hiroshi Harada

    2005-07-01

    Full Text Available Solid tumors containing more hypoxic regions show a more malignant phenotype by increasing the expression of genes encoding angiogenic and metastatic factors. Hypoxia-inducible factor-1 (HIF-1 is a master transcriptional activator of such genes, and thus, imaging and targeting hypoxic tumor cells where HIF-1 is active are important in cancer therapy. In the present study, HIF-1 activity was monitored via an optical in vivo imaging system by using a luciferase reporter gene under the regulation of an artificial HIF-1-dependent promoter, 5HRE. To monitor tumor hypoxia, we isolated a stable reporter-transfectant, HeLa/5HRE-Luc, which expressed more than 100-fold luciferase in response to hypoxic stress, and observed bioluminescence from its xenografts. Immunohistochemical analysis of the xenografts with a hypoxia marker, pimonidazole, confirmed that the luciferase-expressing cells were hypoxic. Evaluation of the efficacy of a hypoxia-targeting prodrug, TOP3, using this optical imaging system revealed that hypoxic cells were significantly diminished by TOP3 treatment. Immunohistochemical analysis of the TOP3-treated xenografts confirmed that hypoxic cells underwent apoptosis and were removed after TOP3 treatment. These results demonstrate that this model system using the 5HRE-luciferase reporter construct provides qualitative information (hypoxic status of solid tumors and enables one to conveniently evaluate the efficacy of cancer therapy on hypoxia in malignant solid tumors.

  15. Hypoxia-induced retinopathy model in adult zebrafish

    DEFF Research Database (Denmark)

    Cao, Ziquan; Jensen, Lasse D.; Rouhi, Pegah

    2010-01-01

    Hypoxia-induced vascular responses, including angiogenesis, vascular remodeling and vascular leakage, significantly contribute to the onset, development and progression of retinopathy. However, until recently there were no appropriate animal disease models recapitulating adult retinopathy available....... In this article, we describe protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1: EGFP zebrafish are placed in hypoxic water for 3-10 d and retinal neovascularization is analyzed using confocal microscopy. It usually takes 11 d to obtain conclusive results using the hypoxia......-induced retinopathy model in adult zebrafish. This model provides a unique opportunity to study kinetically the development of retinopathy in adult animals using noninvasive protocols and to assess therapeutic efficacy of orally active antiangiogenic drugs....

  16. Obstructive sleep apnea and cancer: effects of intermittent hypoxia?

    Science.gov (United States)

    Kukwa, Wojciech; Migacz, Ewa; Druc, Karolina; Grzesiuk, Elzbieta; Czarnecka, Anna M

    2015-01-01

    Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment.

  17. Lead intoxication under environmental hypoxia impairs oral health.

    Science.gov (United States)

    Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Martínez, María Pilar; Conti, María Ines

    2014-01-01

    We have reported that chronic lead intoxication under hypoxic environment induces alveolar bone loss that can lead to periodontal damage with the subsequent loss of teeth. The aim of the present study was to assess the modification of oral inflammatory parameters involved in the pathogenesis of periodontitis in the same experimental model. In gingival tissue, hypoxia increased inducible nitric oxid synthase (iNOS) activity (p lead decreased prostaglandin E2 (PGE2) content (p lead and PGE2 content was increased by both lead and hypoxia (p lead under hypoxic conditions. Results suggest a wide participation of inflammatory markers that mediate alveolar bone loss induced by these environmental conditions. The lack of information regarding oral health in lead-contaminated populations that coexist with hypoxia induced us to evaluate the alteration of inflammatory parameters in rat oral tissues to elucidate the link between periodontal damage and these environmental conditions.

  18. Characterization of CgHIFα-Like, a Novel bHLH-PAS Transcription Factor Family Member, and Its Role under Hypoxia Stress in the Pacific Oyster Crassostrea gigas.

    Directory of Open Access Journals (Sweden)

    Ting Wang

    Full Text Available Hypoxia-inducible factor (HIF, a critical member of the basic-helix-loop-helix (bHLH-containing Per-Arnt-Sim (PAS protein family, is a master transcription factor involved in maintaining oxygen homeostasis. In the present study, we isolated and characterized a novel bHLH-PAS family member, CgHIFα-like gene, from the Pacific oyster Crassostrea gigas, and determined its importance during hypoxia stress. The 3020-bp CgHIFα-like cDNA encoded a protein of 888 amino acids. The predicted CgHIFα-like amino acid sequence was conserved in the N-terminal bHLH, PAS, and PAC domains (but not in the C-terminal domain and was most closely related to the HIF family in the bHLH-PAS protein phylogenic tree. Similar to the mammalian HIF-1α, CgHIFα-like could be expressed as four mRNA isoforms containing alternative 5'-untranslated regions and different translation initiation codons. At the mRNA level, these isoforms were expressed in a tissue-specific manner and showed increased transcription to varying degrees under hypoxic conditions. Additionally, the western blot analysis demonstrated that CgHIFα-like was induced by hypoxia. Electrophoretic mobility shift assay indicated that CgHIFα-like could bind to the hypoxia responsive element (HRE, whereas dual-luciferase reporter analysis demonstrated that CgHIFα-like could transactivate the reporter gene containing the HREs. In addition to CgHIFα-like, we identified CgARNT from the C. gigas, analyzed its expression pattern, and confirmed its interaction with CgHIFα-like using a yeast two-hybrid assay. In conclusion, this is the first report on the cloning and characterization of a novel hypoxia transcription factor in mollusks, which could accumulate under hypoxia and regulate hypoxia related gene expression by binding to HRE and dimerizing with CgARNT. As only one member of HIF has been identified in invertebrates to date, our results provide new insights into the unique mechanisms of hypoxia tolerance in

  19. Results of a Medicare Bundled Payments for Care Improvement Initiative for Chronic Obstructive Pulmonary Disease Readmissions.

    Science.gov (United States)

    Bhatt, Surya P; Wells, J Michael; Iyer, Anand S; Kirkpatrick, deNay P; Parekh, Trisha M; Leach, Lauren T; Anderson, Erica M; Sanders, J Greg; Nichols, Jessica K; Blackburn, Cindy C; Dransfield, Mark T

    2017-05-01

    Approximately 20% of Medicare beneficiaries hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) are readmitted within 30 days of discharge. In addition to implementing penalties for excess readmissions, the U.S. Centers for Medicare and Medicaid Services has developed Bundled Payments for Care Improvement (BPCI) initiatives to improve outcomes and control costs. To evaluate whether a comprehensive COPD multidisciplinary intervention focusing on inpatient, transitional, and outpatient care as part of our institution's BPCI participation would reduce 30-day all-cause readmission rates for COPD exacerbations and reduce overall costs. We performed a pre-postintervention study comparing all-cause readmissions and costs after index hospitalization for Medicare-only patients with acute exacerbation of COPD. The primary outcome was the difference in 30-day all-cause readmission rate compared with historical control subjects; secondary outcomes included the 90-day all-cause readmission rate and also health care costs compared with BPCI target prices. Seventy-eight consecutive Medicare patients were prospectively enrolled in the BPCI intervention in 2014 and compared with 109 patients in the historical group from 2012. Patients in BPCI were more likely to receive regular follow-up phone calls, pneumococcal and influenza vaccines, home health care, durable medical equipment, and pulmonary rehabilitation, and to attend pulmonary clinic. There was no difference in all-cause readmission rates at 30 days (BPCI, 12 events [15.4%] vs. non-BPCI, 19 events [17.4%]; P = 0.711), and 90 days (21 [26.9%] vs. 37 [33.9%]; P = 0.306). Compared with BPCI target prices, we incurred 4.3% lower 90-day costs before accounting for significant investment from the health system. A Medicare BPCI intervention did not reduce 30-day all-cause readmission rates or overall costs after hospitalization for acute exacerbation of COPD. Although additional studies

  20. Results From the Audit of DOD’s American Recovery and Reinvestment Act of 2009 Initial Data Quality Review Implementation

    Science.gov (United States)

    2009-11-03

    Results From the Audit of DoD’s American Recovery and Reinvestment Act of 2009 Initial Data Quality Review Implementation Memorandum No. D-2010-RAM...number. 1. REPORT DATE 03 NOV 2009 2. REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Results From the Audit of...SUBJECT: Results From the Audit of DOD’ s American Recovery and Reinvestment Act of2009 Initial Data Quality Review Implementation (Report No. D

  1. Quercetin enhances hypoxia-mediated apoptosis via direct inhibition of AMPK activity in HCT116 colon cancer.

    Science.gov (United States)

    Kim, Hak-Su; Wannatung, Tirawat; Lee, Sooho; Yang, Woo Kyeom; Chung, Sung Hyun; Lim, Jong-Seok; Choe, Wonchae; Kang, Insug; Kim, Sung-Soo; Ha, Joohun

    2012-09-01

    Tumor hypoxia is considered the best validated target in clinical oncology because of its significant contribution to chemotherapy failure and drug resistance. As an approach to target hypoxia, we assessed the potential of quercetin, a flavonoid widely distributed in plants, as a anticancer agent under hypoxic conditions and examined its pharmacological mechanisms by primarily focusing on the role of AMP-activated protein kinase (AMPK). Quercetin significantly attenuated tumor growth in an HCT116 cancer xenograft in vivo model with a substantial reduction of AMPK activity. In a cell culture system, quercetin more dramatically induced apoptosis of HCT116 cancer cells under hypoxic conditions than normoxic conditions, and this was tightly associated with inhibition of hypoxia-induced AMPK activity. An in vitro kinase assay demonstrated that quercetin directly inhibits AMPK activity. Inhibition of AMPK by expressing a dominant-negative form resulted in an increase of apoptosis under hypoxia, and a constitutively active form of AMPK effectively blocked quercetin-induced apoptosis under hypoxia. Collectively, our data suggest that quercetin directly inhibits hypoxia-induced AMPK, which plays a protective role against hypoxia. Quercetin also reduced the activity of hypoxia-inducible factor-1 (HIF-1), a major transcription factor for adaptive cellular response to hypoxia. Moreover, quercetin sensitized HCT116 cancer cells to the anticancer drugs cisplatin and etoposide under hypoxic conditions. Our findings suggest that AMPK may serve as a novel target for overcoming tumor hypoxia-associated negative aspects.

  2. REFIR/BB initial observations in the water vapour rotational band: Results from a field campaign

    International Nuclear Information System (INIS)

    Esposito, F.; Grieco, G.; Leone, L.; Restieri, R.; Serio, C.; Bianchini, G.; Palchetti, L.; Pellegrini, M.; Cuomo, V.; Masiello, G.; Pavese, G.

    2007-01-01

    There is a growing interest in the far infrared spectral region 17-50 μm as a remote sensing tool in atmospheric sciences, since this portion of the spectrum contains the characteristic molecular rotational band for water vapour. Much of the Earth energy lost to space is radiated through this spectral region. The Radiation Explorer in the Far InfraRed Breadboard (REFIR/BB) spectrometer was born because of the quest to make observations in the far infrared. REFIR/BB is a Fourier Transform Spectrometer with a sampling resolution of 0.5 cm -1 and it was tested for the first time in the field to check its reliability and radiometric performance. The field campaign was held at Toppo di Castelgrande (40 o 49' N, 15 o 27' E, 1258 m a. s. l.), a mountain site in South Italy. The spectral and radiometric performance of the instrument and initial observations are shown in this paper. Comparisons to both (1) BOMEM MR100 Fourier Transform spectrometer observations and (2) line-by-line radiative transfer calculations for selected clear sky are presented and discussed. These comparisons (1) show a very nice agreement between radiance measured by REFIR/BB and by BOMEM MR100 and (2) demonstrate that REFIR/BB accurately observes the very fine spectral structure in the water vapour rotational band

  3. Core competencies for emergency medicine clerkships: results of a Canadian consensus initiative.

    Science.gov (United States)

    Penciner, Rick; Woods, Robert A; McEwen, Jill; Lee, Richard; Langhan, Trevor; Bandiera, Glen

    2013-01-01

    There is no consensus on what constitutes the core competencies for emergency medicine (EM) clerkship rotations in Canada. Existing EM curricula have been developed through informal consensus and often focus on EM content to be known at the end of training rather than what is an appropriate focus for a time-limited rotation in EM. We sought to define the core competencies for EM clerkship in Canada through consensus among an expert panel of Canadian EM educators. We used a modified Delphi method and the CanMEDS 2005 Physician Competency Framework to develop a consensus among expert EM educators from across Canada. Thirty experts from nine different medical schools across Canada participated on the panel. The initial list consisted of 152 competencies organized in the seven domains of the CanMEDS 2005 Physician Competency Framework. After the second round of the Delphi process, the list of competencies was reduced to 62 (59% reduction). A complete list of competencies is provided. This study established a national consensus defining the core competencies for EM clerkship in Canada.

  4. Initial results for a 170 GHz high power ITER waveguide component test stand

    Science.gov (United States)

    Bigelow, Timothy; Barker, Alan; Dukes, Carl; Killough, Stephen; Kaufman, Michael; White, John; Bell, Gary; Hanson, Greg; Rasmussen, Dave

    2014-10-01

    A high power microwave test stand is being setup at ORNL to enable prototype testing of 170 GHz cw waveguide components being developed for the ITER ECH system. The ITER ECH system will utilize 63.5 mm diameter evacuated corrugated waveguide and will have 24 >150 m long runs. A 170 GHz 1 MW class gyrotron is being developed by Communications and Power Industries and is nearing completion. A HVDC power supply, water-cooling and control system has been partially tested in preparation for arrival of the gyrotron. The power supply and water-cooling system are being designed to operate for >3600 second pulses to simulate the operating conditions planned for the ITER ECH system. The gyrotron Gaussian beam output has a single mirror for focusing into a 63.5 mm corrugated waveguide in the vertical plane. The output beam and mirror are enclosed in an evacuated duct with absorber for stray radiation. Beam alignment with the waveguide is a critical task so a combination of mirror tilt adjustments and a bellows for offsets will be provided. Analysis of thermal patterns on thin witness plates will provide gyrotron mode purity and waveguide coupling efficiency data. Pre-prototype waveguide components and two dummy loads are available for initial operational testing of the gyrotron. ORNL is managed by UT-Battelle, LLC, for the U.S. Dept. of Energy under Contract DE-AC-05-00OR22725.

  5. Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture.

    Science.gov (United States)

    Solanki, P; Prasad, D; Muthuraju, S; Sharma, A K; Singh, S B; Ilavzhagan, G

    2011-04-01

    The present study investigates the potential of Piracetam and Vinpocetine (nootropic drugs, known to possess neuroprotective properties) in preventing hypoxia-reoxygenation induced oxidative stress in primary hippocampal cell culture. The hippocampal culture was exposed to hypoxia (95% N(2), 5% CO(2)) for 3h and followed by 1h of reoxygenation (21% O(2) and 5% CO(2)) at 37 °C. The primary hippocampal cultures were supplemented with the optimum dose of Piracetam and Vinpocetine, independently, and the cultures were divided into six groups, viz. Control/Normoxia, Hypoxia, Hypoxia+Piracetam, Hypoxia+Vinpocetine, Normoxia + Piracetam and Normoxia+Vinpocetine. The cell-viability assays and biochemical oxidative stress parameters were evaluated for each of the six groups. Administration of 1mM Piracetam or 500 nM Vinpocetine significantly prevents the culture from hypoxia-reoxygenation injury when determined by Neutral Red assay, LDH release and Acetylcholine esterase activity. Results showed that Piracetam and Vinpocetine supplementation significantly prevented the fall of mitochondrial membrane potential, rise in ROS generation and reduction in antioxidant levels associated with the hypoxia-reoxygenation injury. In conclusion, the present study establishes that both Piracetam and Vinpocetine give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal cell culture. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells

    International Nuclear Information System (INIS)

    Liu, Junye; Zhang, Jing; Wang, Xiaowu; Li, Yan; Chen, Yongbin; Li, Kangchu; Zhang, Jian; Yao, Libo; Guo, Guozhen

    2010-01-01

    Hypoxia inducible factor 1 (HIF-1), the key mediator of hypoxia signaling pathways, has been shown involved in hypoxia-induced radioresistance. However, the underlying mechanisms are unclear. The present study demonstrated that both hypoxia and hypoxia mimetic cobalt chloride could increase the radioresistance of human cervical cancer Hela cells. Meanwhile, ectopic expression of HIF-1 could enhance the resistance of Hela cells to radiation, whereas knocking-down of HIF-1 could increase the sensitivity of Hela cells to radiation in the presence of hypoxia. N-Myc downstream-regulated gene 2 (NDRG2), a new HIF-1 target gene identified in our lab, was found to be upregulated by hypoxia and radiation in a HIF-1-dependent manner. Overexpression of NDRG2 resulted in decreased sensitivity of Hela cells to radiation while silencing NDRG2 led to radiosensitization. Moreover, NDRG2 was proved to protect Hela cells from radiation-induced apoptosis and abolish radiation-induced upregulation of Bax. Taken together, these data suggest that both HIF-1 and NDRG2 contribute to hypoxia-induced tumor radioresistance and that NDRG2 acts downstream of HIF-1 to promote radioresistance through suppressing radiation-induced Bax expression. It would be meaningful to further explore the clinical application potential of HIF-1 and NDRG2 blockade as radiosensitizer for tumor therapy.

  7. Extreme hypoxia tolerance of naked mole-rat brain.

    Science.gov (United States)

    Larson, John; Park, Thomas J

    2009-12-09

    Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

  8. Culture media from hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury.

    Science.gov (United States)

    Hummitzsch, Lars; Zitta, Karina; Bein, Berthold; Steinfath, Markus; Albrecht, Martin

    2014-03-10

    Remote ischemic preconditioning (RIPC) is a phenomenon, whereby short episodes of non-lethal ischemia to an organ or tissue exert protection against ischemia/reperfusion injury in a distant organ. However, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms within the target organ and the released factors. Here we established a human cell culture model to investigate cellular and molecular effects of RIPC and to identify factors responsible for RIPC-mediated intestinal protection. Human umbilical vein cells (HUVEC) were exposed to repeated episodes of hypoxia (3 × 15 min) and conditioned culture media (CM) were collected after 24h. Human intestinal cells (CaCo-2) were cultured with or without CM and subjected to 90 min of hypoxia/reoxygenation injury. Reverse transcription-polymerase chain reaction, Western blotting, gelatin zymography, hydrogen peroxide measurements and lactate dehydrogenase (LDH) assays were performed. In HUVEC cultures hypoxic conditioning did not influence the profile of secreted proteins but led to an increased gelatinase activity (Pcultures 90 min of hypoxia/reoxygenation resulted in morphological signs of cell damage, increased LDH levels (Pculture model may help to unravel RIPC-mediated cellular events and to identify molecules released by RIPC. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Effects of hypoxia on human cancer cell line chemosensitivity

    Science.gov (United States)

    2013-01-01

    Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

  10. Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.

    Science.gov (United States)

    Aprelikova, Olga; Chandramouli, Gadisetti V R; Wood, Matthew; Vasselli, James R; Riss, Joseph; Maranchie, Jodi K; Linehan, W Marston; Barrett, J Carl

    2004-06-01

    Hypoxia and induction of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) is a hallmark of many tumors. Under normal oxygen tension HIF-alpha subunits are rapidly degraded through prolyl hydroxylase dependent interaction with the von Hippel-Lindau (VHL) tumor suppressor protein, a component of E3 ubuiquitin ligase complex. Using microarray analysis of VHL mutated and re-introduced cells, we found that one of the prolyl hydroxylases (PHD3) is coordinately expressed with known HIF target genes, while the other two family members (PHD1 and 2) did not respond to VHL. We further tested the regulation of these genes by HIF-1 and HIF-2 and found that siRNA targeted degradation of HIF-1alpha and HIF-2alpha results in decreased hypoxia-induced PHD3 expression. Ectopic overexpression of HIF-2alpha in two different cell lines provided a much better induction of PHD3 gene than HIF-1alpha. In contrast, we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF-2alpha. However, induction of PHD2 by hypoxia has HIF-1-independent and -dependent components. Short-term hypoxia (4 h) results in induction of PHD2 independent of HIF-1, while PHD2 accumulation by prolonged hypoxia (16 h) was decreased by siRNA-mediated degradation of HIF-1alpha subunit. These data further advance our understanding of the differential role of HIF factors and putative feedback loop in HIF regulation. Copyright 2004 Wiley-Liss, Inc.

  11. 75 FR 71072 - Initiation and Preliminary Results of Antidumping Duty Changed Circumstances Review: Certain...

    Science.gov (United States)

    2010-11-22

    ... factors including, but not limited to: (1) Management; (2) production facilities; (3) supplier relationships; and (4) customer base. See Brass Sheet and Strip from Canada: Final Results of Antidumping Duty... y Placa resulted in little or no change in management, production facilities, supplier relationships...

  12. Lipid peroxidation in neonatal mouse brain subjected to two different types of hypoxia.

    Science.gov (United States)

    Hasegawa, K; Yoshioka, H; Sawada, T; Nishikawa, H

    1991-01-01

    To elucidate the role of free radicals in the pathogenesis of neonatal hypoxic encephalopathy, we determined the content of thiobarbituric acid reactants (TBARs), as an index of lipid peroxidation related with a free radical reaction, in the brains of newborn mice during hypoxia and recovery from hypoxia. Hypoxic stress was induced by 100% nitrogen gas breathing (N2 group) or 100% carbon dioxide gas breathing (CO2 group). TBARs increased with 20 minutes of hypoxia and returned to the control level during the recovery period in both groups. The increase in TBARs in the CO2 group was greater than that in the N2 group. These results may suggest that free radical reaction occurs during the hypoxic period and that CO2 hypoxia is more effective on free radical production in the newborn brain than N2 hypoxia.

  13. Observations of Fabric Development in Polycrystalline Ice at Basal Pressures: Methods and Initial Results

    Science.gov (United States)

    Breton, D. J.; Baker, I.; Cole, D. M.

    2012-12-01

    Understanding and predicting the flow of polycrystalline ice is crucial to ice sheet modeling and paleoclimate reconstruction from ice cores. Ice flow rates depend strongly on the fabric (i.e. the distribution of grain sizes and crystallographic orientations) which evolves over time and enhances the flow rate in the direction of applied stress. The mechanisms for fabric evolution in ice have been extensively studied at atmospheric pressures, but little work has been done to observe these processes at the high pressures experienced deep within ice sheets where long-term changes in ice rheology are expected to have significance. We conducted compressive creep tests on a 917 kg m-3 polycrystalline ice specimen at 20 MPa hydrostatic pressure, thus simulating ~2,000 m depth. Initial specimen grain orientations were random, typical grain diameters were 1.2 mm, and the applied creep stress was 0.3 MPa. Subsequent microstructural analyses on the deformed specimen and a similarly prepared, undeformed specimen allowed characterization of crystal fabric evolution under pressure. Our microstructural analysis technique simultaneously collected grain shape and size data from Scanning Electron Microscope (SEM) micrographs and obtained crystallographic orientation data via Electron BackScatter Diffraction (EBSD). Combining these measurements allows rapid analysis of the ice fabric over large numbers of grains, yielding statistically useful numbers of grain size and full c- and a-axis grain orientation data. The combined creep and microstructural data demonstrate pressure-dependent effects on the mechanical and microstructural evolution of polycrystalline ice. We discuss possible mechanisms for the observed phenomena, and future directions for hydrostatic creep testing.

  14. Regional Collaboration Among Urban Area Security Initiative Regions: Results of the Johns Hopkins Urban Area Survey

    Science.gov (United States)

    Bowman, Calvin; Barnett, Daniel J.; Resnick, Beth A.; Frattaroli, Shannon; Rutkow, Lainie

    2014-01-01

    Regional collaboration has been identified as a potential facilitator of public health preparedness efforts. The Urban Area Security Initiative (UASI) grant program, administered by the Federal Emergency Management Agency (FEMA) since 2003, has provided 64 high-risk metropolitan areas funding to enhance their regional preparedness capabilities. This study describes informal and formal regional collaboration infrastructure, as well as regional collaboration–related activities and assessment methods, in FFY2010 UASI regions. A cross-sectional online survey was administered via Survey Monkey from September through December 2013. Points of contact from FFY2010 funded UASI metropolitan areas completed the survey, with a response rate of 77.8% (n=49). Summary statistics were calculated to describe the current informal and formal regional collaboration infrastructure. Additionally, the cross-sectional survey collected rates of agreement with 8 collaborative preparedness statements at 3 time points. The survey found that UASI regions are engaging in collaborative activities and investments to build capabilities, with most collaboration occurring in the prevention, protection, and response mission areas. Collaborative relationships in preparedness among emergency managers and municipal chief executive officers improved during the FFY2010 UASI performance period compared to the pre-UASI award period, with lasting effects. The majority of UASI regions reported conducting independent assessments of capabilities and their measurement at the UASI region level. Urban areas that received a FFY2010 UASI grant award are engaging in collaborative activities and have established interjurisdictional relationships in preparedness. The use of grant funds to encourage collaboration in preparedness has the potential to leverage limited resources and promote informed investments. PMID:25398073

  15. Regional collaboration among Urban Area Security Initiative regions: results of the Johns Hopkins urban area survey.

    Science.gov (United States)

    Errett, Nicole A; Bowman, Calvin; Barnett, Daniel J; Resnick, Beth A; Frattaroli, Shannon; Rutkow, Lainie

    2014-01-01

    Regional collaboration has been identified as a potential facilitator of public health preparedness efforts. The Urban Area Security Initiative (UASI) grant program, administered by the Federal Emergency Management Agency (FEMA) since 2003, has provided 64 high-risk metropolitan areas funding to enhance their regional preparedness capabilities. This study describes informal and formal regional collaboration infrastructure, as well as regional collaboration-related activities and assessment methods, in FFY2010 UASI regions. A cross-sectional online survey was administered via Survey Monkey from September through December 2013. Points of contact from FFY2010 funded UASI metropolitan areas completed the survey, with a response rate of 77.8% (n=49). Summary statistics were calculated to describe the current informal and formal regional collaboration infrastructure. Additionally, the cross-sectional survey collected rates of agreement with 8 collaborative preparedness statements at 3 time points. The survey found that UASI regions are engaging in collaborative activities and investments to build capabilities, with most collaboration occurring in the prevention, protection, and response mission areas. Collaborative relationships in preparedness among emergency managers and municipal chief executive officers improved during the FFY2010 UASI performance period compared to the pre-UASI award period, with lasting effects. The majority of UASI regions reported conducting independent assessments of capabilities and their measurement at the UASI region level. Urban areas that received a FFY2010 UASI grant award are engaging in collaborative activities and have established interjurisdictional relationships in preparedness. The use of grant funds to encourage collaboration in preparedness has the potential to leverage limited resources and promote informed investments.

  16. EPA program to demonstrate mitigation measures for indoor radon: initial results

    International Nuclear Information System (INIS)

    Henschel, D.B.; Scott, A.G.

    1986-01-01

    EPA has installed radon mitigation techniques in 18 concrete block basement homes in the Reading Prong region of eastern Pennsylvania. Three alternative active soil ventilation approaches were tested: suction on the void network within the concrete block basement walls; suction on the footing drain tile system; and suction on the aggregate underneath the concrete slab. The initial 18 mitigation installations were designed to demonstrate techniques which would have low to moderate installation and operating costs. Where effective closure of major openings in the block walls is possible, suction on the wall voids has proved to be extremely effective, able to reduce homes having very high radon Working Levels (up to 7 WL) to 0.02 WL and less. However, where inaccessible major openings are concealed within the wall, it is more difficult and/or more expensive to develop adequate suction on the void network, and performance is reduced. Testing is continuing to demonstrate the steps required to achieve high performance with wall suction in homes with such difficult-to close walls. Drain tile suction can be very effective where the drain tiles completely surround the home; drain tile suction is the least expensive and most aesthetic of the active soil ventilation approaches, but appears susceptible to spikes in radon levels when the basement is depressurized. Sub-slab suction as tested in this study - with one or two individual suction points in the slab - does not appear adequate to ensure sustained high levels of reduction on block wall basement homes; it appears to effectively treat slab-related soil gas entry routes so long as a uniform layer of aggregate is present, but it does not appear to effectively treat the wall-related entry routes. Closure of major openings might have improved sub-slab suction performance. 5 figures, 3 tables

  17. Imaging of tumor viability in lung cancer. Initial results using 23Na-MRI

    International Nuclear Information System (INIS)

    Henzler, T.; Apfaltrer, P.; Haneder, S.; Schoenberg, S.O.; Fink, C.; Konstandin, S.; Schad, L.; Schmid-Bindert, G.; Manegold, C.; Wenz, F.

    2012-01-01

    23 Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23 Na-MRI in patients with lung cancer. Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23 Na-MRI images was proven by comparison and fusion of 23 Na-MRI with 1 H-MR, CT and FDG-PET-CT images. 23 Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). All 23 Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23 Na-MRI images with 1 H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 x 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 x 103 and 1.10, respectively. 23 Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response. (orig.)

  18. Successfully Reducing Hospitalizations of Nursing Home Residents: Results of the Missouri Quality Initiative.

    Science.gov (United States)

    Rantz, Marilyn J; Popejoy, Lori; Vogelsmeier, Amy; Galambos, Colleen; Alexander, Greg; Flesner, Marcia; Crecelius, Charles; Ge, Bin; Petroski, Gregory

    2017-11-01

    The goals of the Missouri Quality Initiative (MOQI) for long-stay nursing home residents were to reduce the frequency of avoidable hospital admissions and readmissions, improve resident health outcomes, improve the process of transitioning between inpatient hospitals and nursing facilities, and reduce overall healthcare spending without restricting access to care or choice of providers. The MOQI was one of 7 program sites in the United States, with specific interventions unique to each site tested for the Centers for Medicaid and Medicare Services (CMS) Innovations Center. A prospective, single group intervention design, the MOQI included an advanced practice registered nurse (APRN) embedded full-time within each nursing home (NH) to influence resident care outcomes. Data were collected continuously for more than 3 years from an average of 1750 long-stay Medicare, Medicaid, and private pay residents living each day in 16 participating nursing homes in urban, metro, and rural communities within 80 miles of a major Midwestern city in Missouri. Performance feedback reports were provided to each facility summarizing their all-cause hospitalizations and potentially avoidable hospitalizations as well as a support team of social work, health information technology, and INTERACT/Quality Improvement Coaches. The MOQI achieved a 30% reduction in all-cause hospitalizations and statistically significant reductions in 4 single quarters of the 2.75 years of full implementation of the intervention for long-stay nursing home residents. As the population of older people explodes in upcoming decades, it is critical to find good solutions to deal with increasing costs of health care. APRNs, working with multidisciplinary support teams, are a good solution to improving care and reducing costs if all nursing home residents have access to APRNs nationwide. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  19. Measuring success: results from a national survey of recruitment and retention initiatives in the nursing workforce.

    Science.gov (United States)

    Brooks Carthon, J Margo; Nguyen, Thai-Huy; Chittams, Jesse; Park, Elizabeth; Guevara, James

    2014-01-01

    The purpose of this study was to identify common components of diversity pipeline programs across a national sample of nursing institutions and determine what effect these programs have on increasing underrepresented minority enrollment and graduation. Linked data from an electronic survey conducted November 2012 to March 2013 and American Association of Colleges of Nursing baccalaureate graduation and enrollment data (2008 and 2012). Academic and administrative staff of 164 nursing schools in 26 states, including Puerto Rico in the United States. Chi-square statistics were used to (1) describe organizational features of nursing diversity pipeline programs and (2) determine significant trends in underrepresented minorities' graduation and enrollment between nursing schools with and without diversity pipeline programs Twenty percent (n = 33) of surveyed nursing schools reported a structured diversity pipeline program. The most frequent program measures associated with pipeline programs included mentorship, academic, and psychosocial support. Asian, Hispanic, and Native Hawaiian/Pacific Islander nursing student enrollment increased between 2008 and 2012. Hispanic/Latino graduation rates increased (7.9%-10.4%, p = .001), but they decreased among Black (6.8%-5.0%, p = .004) and Native American/Pacific Islander students (2.1 %-0.3%, p ≥ .001). Nursing diversity pipeline programs are associated with increases in nursing school enrollment and graduation for some, although not all, minority students. Future initiatives should build on current trends while creating targeted strategies to reverse downward graduation trends among Black, Native American, and Pacific Island nursing students. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The green bank northern celestial cap pulsar survey. I. Survey description, data analysis, and initial results

    Energy Technology Data Exchange (ETDEWEB)

    Stovall, K.; Dartez, L. P.; Ford, A. J.; Garcia, A.; Hinojosa, J.; Jenet, F. A.; Leake, S. [Center for Advanced Radio Astronomy, University of Texas at Brownsville, One West University Boulevard, Brownsville, TX 78520 (United States); Lynch, R. S.; Archibald, A. M.; Karako-Argaman, C.; Kaspi, V. M. [Department of Physics, McGill University, 3600 University Street, Montreal, QC H3A 2T8 (Canada); Ransom, S. M. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22901 (United States); Banaszak, S.; Biwer, C. M.; Day, D.; Flanigan, J.; Kaplan, D. L. [Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211 (United States); Boyles, J. [Department of Physics and Astronomy, Western Kentucky University, Bowling Green, KY 42101 (United States); Hessels, J. W. T.; Kondratiev, V. I., E-mail: stovall.kevin@gmail.com [ASTRON, the Netherlands Institute for Radio Astronomy, Postbus 2, 7990 AA Dwingeloo (Netherlands); and others

    2014-08-10

    We describe an ongoing search for pulsars and dispersed pulses of radio emission, such as those from rotating radio transients (RRATs) and fast radio bursts, at 350 MHz using the Green Bank Telescope. With the Green Bank Ultimate Pulsar Processing Instrument, we record 100 MHz of bandwidth divided into 4096 channels every 81.92 μs. This survey will cover the entire sky visible to the Green Bank Telescope (δ > –40°, or 82% of the sky) and outside of the Galactic Plane will be sensitive enough to detect slow pulsars and low dispersion measure (<30 pc cm{sup –3}) millisecond pulsars (MSPs) with a 0.08 duty cycle down to 1.1 mJy. For pulsars with a spectral index of –1.6, we will be 2.5 times more sensitive than previous and ongoing surveys over much of our survey region. Here we describe the survey, the data analysis pipeline, initial discovery parameters for 62 pulsars, and timing solutions for 5 new pulsars. PSR J0214+5222 is an MSP in a long-period (512 days) orbit and has an optical counterpart identified in archival data. PSR J0636+5129 is an MSP in a very short-period (96 minutes) orbit with a very low mass companion (8 M{sub J}). PSR J0645+5158 is an isolated MSP with a timing residual RMS of 500 ns and has been added to pulsar timing array experiments. PSR J1434+7257 is an isolated, intermediate-period pulsar that has been partially recycled. PSR J1816+4510 is an eclipsing MSP in a short-period orbit (8.7 hr) and may have recently completed its spin-up phase.

  1. Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis

    Directory of Open Access Journals (Sweden)

    Malik Assaf

    2012-11-01

    Full Text Available Abstract Background The development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research. Results Using microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals. Conclusions This is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to

  2. Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter

    Directory of Open Access Journals (Sweden)

    Barker Bridget M

    2012-02-01

    Full Text Available Abstract Background Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major

  3. Ageing and cardiorespiratory response to hypoxia.

    Science.gov (United States)

    Lhuissier, François J; Canouï-Poitrine, Florence; Richalet, Jean-Paul

    2012-11-01

    The risk of severe altitude-induced diseases is related to ventilatory and cardiac responses to hypoxia and is dependent on sex, age and exercise training status. However, it remains unclear how ageing modifies these physiological adaptations to hypoxia. We assessed the physiological responses to hypoxia with ageing through a cross-sectional 20 year study including 4675 subjects (2789 men, 1886 women; 14-85 years old) and a longitudinal study including 30 subjects explored at a mean 10.4 year interval. The influence of sex, training status and menopause was evaluated. The hypoxia-induced desaturation and the ventilatory and cardiac responses to hypoxia at rest and exercise were measured. In men, ventilatory response to hypoxia increased (P ageing. Cardiac response to hypoxia was blunted with ageing in both sexes (P ageing. These adaptive responses were less pronounced or absent in post-menopausal women (P ageing in men while cardiac response is blunted with ageing in both sexes. Training aggravates desaturation at exercise in hypoxia, improves the ventilatory response and limits the ageing-induced blunting of cardiac response to hypoxia. Training limits the negative effects of menopause in cardiorespiratory adaptations to hypoxia.

  4. Exercise Improves Mood State in Normobaric Hypoxia.

    Science.gov (United States)

    Seo, Yongsuk; Fennell, Curtis; Burns, Keith; Pollock, Brandon S; Gunstad, John; McDaniel, John; Glickman, Ellen

    2015-11-01

    The purpose of this study was to quantify the efficacy of using exercise to alleviate the impairments in mood state associated with hypoxic exposure. Nineteen young, healthy men completed Automated Neuropsychological Assessment Metrics-4(th) Edition (ANAM4) versions of the mood state test before hypoxia exposure, after 60 min of hypoxia exposure (12.5% O(2)), and during and after two intensities of cycling exercise (40% and 60% adjusted Vo(2max)) under the same hypoxic conditions. Peripheral oxygen saturation (Spo(2)) and regional cerebral oxygen saturation (rSo(2)) were continuously monitored. At rest in hypoxia, Total Mood Disturbance (TMD) was significantly increased compared to baseline in both the 40% and 60% groups. TMD was significantly decreased during exercise compared to rest in hypoxia. TMD was also significantly decreased during recovery compared to rest in hypoxia. Spo(2) significantly decreased at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. Regional cerebral oxygen saturation was also reduced at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. The current study demonstrated that exercise at 40% and 60% of adjusted Vo(2max) attenuated the adverse effects of hypoxia on mood. These findings may have significant applied value, as negative mood states are known to impair performance in hypoxia. Further studies are needed to replicate the current finding and to clarify the possible mechanisms associated with the potential benefits of exercise on mood state in normobaric hypoxia.

  5. Some initial results from the new SLAC [Stanford Linear Accelerator Center] permeameter

    International Nuclear Information System (INIS)

    Cobb, J.K.; Early, R.A.

    1990-01-01

    A new permeameter has been built and is now available for testing samples of steel and other ferromagnetic materials for their magnetic characteristics such as permeability, remanent induction, coercive force and saturation induction. The present range of operation for the permeameter is from 0.5 Oe to 1250 Oe. Results are presented for two samples of low-carbon steel as well as some preliminary results for Vanadium Permendur. 4 refs., 8 figs

  6. Initial experience with a group presentation of study results to research participants

    Directory of Open Access Journals (Sweden)

    Bent Stephen

    2008-03-01

    Full Text Available Abstract Background Despite ethical imperatives, informing research participants about the results of the studies in which they take part is not often performed. This is due, in part, to the costs and burdens of communicating with each participant after publication of the results. Methods Following the closeout and publication of a randomized clinical trial of saw palmetto for treatment of symptoms of benign prostatic hyperplasia, patients were invited back to the research center to participate in a group presentation of the study results. Results Approximately 10% of participants attended one of two presentation sessions. Reaction to the experience of the group presentation was very positive among the attendees. Conclusion A group presentation to research participants is an efficient method of communicating study results to those who desire to be informed and was highly valued by those who attended. Prospectively planning for such presentations and greater scheduling flexibility may result in higher attendance rates. Trial Registration Number Clinicaltrials.gov #NCT00037154

  7. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  8. The effects of exercise under hypoxia on cognitive function.

    Directory of Open Access Journals (Sweden)

    Soichi Ando

    Full Text Available Increasing evidence suggests that cognitive function improves during a single bout of moderate exercise. In contrast, exercise under hypoxia may compromise the availability of oxygen. Given that brain function and tissue integrity are dependent on a continuous and sufficient oxygen supply, exercise under hypoxia may impair cognitive function. However, it remains unclear how exercise under hypoxia affects cognitive function. The purpose of this study was to examine the effects of exercise under different levels of hypoxia on cognitive function. Twelve participants performed a cognitive task at rest and during exercise at various fractions of inspired oxygen (FIO2: 0.209, 0.18, and 0.15. Exercise intensity corresponded to 60% of peak oxygen uptake under normoxia. The participants performed a Go/No-Go task requiring executive control. Cognitive function was evaluated using the speed of response (reaction time and response accuracy. We monitored pulse oximetric saturation (SpO2 and cerebral oxygenation to assess oxygen availability. SpO2 and cerebral oxygenation progressively decreased during exercise as the FIO2 level decreased. Nevertheless, the reaction time in the Go-trial significantly decreased during moderate exercise. Hypoxia did not affect reaction time. Neither exercise nor difference in FIO2 level affected response accuracy. An additional experiment indicated that cognitive function was not altered without exercise. These results suggest that the improvement in cognitive function is attributable to exercise, and that hypoxia has no effects on cognitive function at least under the present experimental condition. Exercise-cognition interaction should be further investigated under various environmental and exercise conditions.

  9. Initial results from a reconnaissance of cyanobacteria and associated toxins in Illinois, August--October 2012

    Science.gov (United States)

    Terrio, Paul J.; Ostrodka, Lenna M.; Loftin, Keith A.; Good, Gregg; Holland, Teri

    2013-01-01

    Ten lakes and two rivers in Illinois were sampled in August–October 2012 to determine the concentrations and spatial distribution of cyanobacteria and associated cyanotoxins throughout the State. The reconnaissance was a collaborative effort of the U.S. Geological Survey and the Illinois Environmental Protection Agency. Sample results indicated that concentrations of both total cyanobacterial cells and microcystin were commonly at levels likely to result in adverse human health effects, according to World Health Organization guidance values. Concentrations generally decreased from August to October following precipitation events and lower temperatures.

  10. Effect of low-frequency low-intensity ultrasound with microbubbles on prostate cancer hypoxia.

    Science.gov (United States)

    Hou, Rui; Xu, Yanjun; Lu, Qijie; Zhang, Yang; Hu, Bing

    2017-10-01

    Angiogenesis plays an important role in tumor growth, invasiveness, and metastasis. It is well established that prostate cancer is exposed to fluctuating oxygen tensions and both acute and chronic hypoxia exist, and these conditions can upregulate angiogenesis-associated proteins such as hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A. Low-frequency low-intensity ultrasound with microbubbles can induce obvious microvessel damage in tumors, cause cell necrosis or apoptosis. However, there is no information about whether the blocking blood effect of low-frequency low-intensity ultrasound with microbubbles has an influence on hypoxia environment of prostate cancer. Therefore, we investigated the impact of different low-frequency low-intensity ultrasound with microbubbles radiation times on prostate tumors, observed the change in the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A protein levels, as well as cell proliferation, apoptosis, and tumor volume. The results indicated that as the radiation was repeated four times on each treatment day, the effects of interruption were durable, the cell proliferation was inhibited, and apoptosis was promoted, and the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A expression levels were lower in the treatment group than in the control group. When the radiation was carried out once per treatment day, the hypoxia response was stimulated, the hypoxia-inducible factor 1 alpha and vascular endothelial growth factor A expression levels were higher compared with the control group, and cell proliferation was promoted. In addition, the tumor volume increased obviously in the hypoxia-stimulated group, whereas tumors grew slowly in the hypoxia-suppressed group. The results of this work demonstrated that under the same conditions, different radiation times of low-frequency low-intensity ultrasound with microbubbles affect the hypoxia response differently, and the

  11. Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents

    International Nuclear Information System (INIS)

    Vacek, A.; Hofer, M.

    2001-01-01

    Aim: Analysis of radioprotective effect of respiratory hypoxia on hemopoietic tissue and enhancement of this effect by hemopoietic activation. Material and methods: In mice breathing hypoxic gas mixture during total body gamma irradiation the recovery of pluripotent and committed granulocyte-macrophage progenitor cells and animal lethality were determined. Results: In mice forced to breathe 10% O 2 and 8% O 2 during irradiation, the oxygen tension in the spleen decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the lethal effect of gamma-rays and improved the recovery of hemopoiesis in compartments of pluripotent and committed progenitor cells. Enhancement of the proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an immunomodulator (dextran sulfate) increased the effect of hypoxic radioprotection, while elimination of proliferative cells by hydroxyurea decreased the radioprotective effect. Adaptation of experimental animals to hypoxic conditions was found to reduce the radioprotective effect without influencing tissue partial oxygen pressure lowered by hypoxic conditions. Conclusion: The data presented confirm the radioprotective effect of 10% and 8% O 2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for further experimental and clinical research aimed at considering differential protection of various tissues by hypoxia. (orig.) [de

  12. Initial Results of an Intercomparison of AMS-Based Atmospheric 14CO2 Measurements

    NARCIS (Netherlands)

    Miller, John; Lehman, Scott; Wolak, Chad; Turnbull, Jocelyn; Dunn, Gregory; Graven, Heather; Keeling, Ralph; Meijer, Harro A. J.; Aerts-Bijma, Anita Th; Palstra, Sanne W. L.; Smith, Andrew M.; Allison, Colin; Southon, John; Xu, Xiaomei; Nakazawa, Takakiyo; Aoki, Shuji; Nakamura, Toshio; Guilderson, Thomas; LaFranchi, Brian; Mukai, Hitoshi; Terao, Yukio; Uchida, Masao; Kondo, Miyuki

    2013-01-01

    This article presents results from the first 3 rounds of an international intercomparison of measurements of Delta(CO2)-C-14 in liter-scale samples of whole air by groups using accelerator mass spectrometry (AMS). The ultimate goal of the intercomparison is to allow the merging of Delta(CO2)-C-14

  13. Electron Beam Return-Current Losses in Solar Flares: Initial Comparison of Analytical and Numerical Results

    Science.gov (United States)

    Holman, Gordon

    2010-01-01

    Accelerated electrons play an important role in the energetics of solar flares. Understanding the process or processes that accelerate these electrons to high, nonthermal energies also depends on understanding the evolution of these electrons between the acceleration region and the region where they are observed through their hard X-ray or radio emission. Energy losses in the co-spatial electric field that drives the current-neutralizing return current can flatten the electron distribution toward low energies. This in turn flattens the corresponding bremsstrahlung hard X-ray spectrum toward low energies. The lost electron beam energy also enhances heating in the coronal part of the flare loop. Extending earlier work by Knight & Sturrock (1977), Emslie (1980), Diakonov & Somov (1988), and Litvinenko & Somov (1991), I have derived analytical and semi-analytical results for the nonthermal electron distribution function and the self-consistent electric field strength in the presence of a steady-state return-current. I review these results, presented previously at the 2009 SPD Meeting in Boulder, CO, and compare them and computed X-ray spectra with numerical results obtained by Zharkova & Gordovskii (2005, 2006). The phYSical significance of similarities and differences in the results will be emphasized. This work is supported by NASA's Heliophysics Guest Investigator Program and the RHESSI Project.

  14. 75 FR 37757 - Frozen Warmwater Shrimp From Vietnam: Initiation and Preliminary Results of Changed-Circumstances...

    Science.gov (United States)

    2010-06-30

    ... including, but not limited to, changes in management, production facilities, supplier relationships, and customer base. See Industrial Phosphoric Acid From Israel: Final Results of Antidumping Duty Changed... Corp. is the successor-in- interest to Phuong Nam Co., Ltd. With respect to management prior to and...

  15. A 10-Year Mechatronics Curriculum Development Initiative: Relevance, Content, and Results--Part I

    Science.gov (United States)

    Das, S.; Yost, S. A.; Krishnan, M.

    2010-01-01

    This paper describes the first phase of a Mechatronics Curriculum Development effort--the design of an "Introduction to Mechatronics" course, the infusion of mechatronics activities throughout the curriculum and in outreach activities, and assessment results. In addition, the relevance and impact of such a curriculum on the education of engineers…

  16. 75 FR 61702 - Notice of Initiation and Preliminary Results of Antidumping Duty Changed Circumstances Review...

    Science.gov (United States)

    2010-10-06

    .../supplier relationships have not changed as a result of the corporate name change. To support its claims, A... 1, 2010, A Foods informed the Department that it changed its name from May Ao and [[Page 61703... that May Ao officially changed its name to A Foods on December 25, 2009. This constitutes changed...

  17. General Atomic HTGR fuel reprocessing pilot plant: results of initial sequential equipment operation

    International Nuclear Information System (INIS)

    1978-09-01

    In September 1977, the processing of 20 large high-temperature gas-cooled reactor (LHTGR) fuel elements was completed sequentially through the head-end cold pilot plant equipment. This report gives a brief description of the equipment and summarizes the results of the sequential operation of the pilot plant. 32 figures, 15 tables

  18. Tether dynamics and control results for tethered satellite system's initial flight

    Science.gov (United States)

    Chapel, Jim D.; Flanders, Howard

    The recent Tethered Satellite System-1 (TSS-1) mission has provided a wealth of data concerning the dynamics of tethered systems in space and has demonstrated the effectiveness of operational techniques designed to control these dynamics. In this paper, we review control techniques developed for managing tether dynamics, and discuss the results of using these techniques for the Tethered Satellite System's maiden flight on STS-46. In particular, the flight results of controlling libration dynamics, string dynamics, and slack tether are presented. These results show that tether dynamics can be safely managed. The overall stability of the system was found to be surprisingly good even at relatively short tether lengths. In fact, the system operated in passive mode at a tether length of 256 meters for over 9 hours. Only monitoring of the system was required during this time. Although flight anomalies prevented the planned deployment to 20 km, the extended operations at shorter tether lengths have proven the viability of using tethers in space. These results should prove invaluable in preparing for future missions with tethered objects in space.

  19. Initial results of combined anterior mitral leaflet extension and myectomy in patients with obstructive hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); L.A. van Herwerden (Lex); D.J. Waldstein; P.N. Ruygrok (Peter); H. Boersma (Eric); M.A. Taams (Meindert); F.J. ten Cate (Folkert)

    1996-01-01

    textabstractObjectives. The purpose of this study was to describe the clinical and functional results of combined anterior mitral leaflet extension and myectomy in patients with hypertrophic obstructive cardiomyopathy. Background. Septal myectomy is the most commonly performed surgical procedure in

  20. Operation results of 3-rd generation nuclear fuel WWER-440 in initial period

    International Nuclear Information System (INIS)

    Adeev, V.; Panov, A.

    2011-01-01

    On unit 4 of Kola NPP trial operation of 3-rd generation's fuel began in 2010. Fuel assemblies of 3-rd generation (FA-3) have a number of design features that provide better operational characteristics. Concise description of a design and the basic advantages of fuel of 3-rd generation are described in articles. Increasing of efficiency of nuclear fuel usage will be achieved by reduction of the parasitic capture of thermal neutrons in constructional materials (weight of zirconium is reduced), optimization of uranium-water relation (increase in fuel elements step), increasing of uranium loading (usage of fuel pellets with increased diameter and without central hole in them). By results of trial operation mass transition to use of given type of assemblies in WWER-440 is possible. This report presents the basic outcomes of the trial operation, a brief survey of the obtained data. The basic characteristics of the reactor core with fuel of 3-rd generation are resulted in work. (authors)

  1. Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

    2017-11-15

    Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism *

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J. P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Dos Santos Coelho, P.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N. M.

    2017-01-01

    Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer...

  3. Design of a low cost miniaturized SFCW GPR with initial results

    Science.gov (United States)

    Duggal, Swati; Sinha, Piyush; Gupta, Manish; Patel, Anand; Vedam, V. V.; Mevada, Pratik; Chavda, Rajesh; Shah, Amita; Putrevu, Deepak

    2016-05-01

    This paper discusses about the design &developmental of Ground Penetrating Radar (GPR), various scientific and commercial applications of GPR along with the testing and results of GPR at Antarctica for Ice thickness measurement. GPR instruments are categorised as per their frequency of operation, which is inversely proportional to the depth of penetration. GPRs are also categorized as per method of operation which is time-domain or frequency-domain. Indian market is presently procuring GPRs from only foreign suppliers. Space Applications Centre (SAC) had taken up GPR as R&D Technological development with a view to benchmark the technology which may be transferred to local industry for mass production of instrument at a relatively cheaper cost (~20 times cheaper). Hence, this instrument presents a viable indigenous alternative. Also, the design and configuration was targeted for terrestrial as well as future interplanetary (Lander/Rover) missions of ISRO to map subsurface features. The developed GPR has a very large bandwidth (100%, i.e. bandwidth of 500MHz with centre-frequency of 500MHz) and high dynamic range along with the advantage of being highly portable (<10kg). The system was configured as a Stepped-Frequency-Continuous-Wave (SFCW) GPR which is a frequency domain GPR with the aim to increase the detection capabilities with respect to current systems. In order to achieve this goal, innovative electronic equipment have been designed and developed. Three prototypes were developed and two of them have been delivered for Indian Scientific Expedition to Antarctica (ISEA) in 2013 and 2014-15, respectively and promising results have been obtained. The results from the same closely compare with that from commercial GPR too.

  4. Initial results of strand produced in Phase 2 of the SSCL Vendor Qualification Program

    International Nuclear Information System (INIS)

    Erdmann, M.; Capone, D. II; Coleman, S.; Jones, B.; Seuntjens, J.

    1993-05-01

    In 1991, the Superconducting Super Collider Laboratory (SSCL) instituted a program to qualify specific superconductor manufacturers for production of cable acceptable for use in both Collider Dipole (CDM) and Quadrupole (CQM) magnets. The SSCL Vendor Qualification Program (VQP) was designed with two Phases. Phase 1 was divided into two additional phases, 1A and 1B, which ran concurrently. In Phase 1B, each vendor was directed to manufacture roughly 3000 kg of cable using a ''baseline'' process. The baseline process was agreed to by both the SSCL and the vendor at the beginning of the VQP. In this phase, process control was closely monitored with the use of statistical methods and each vendor was graded based on these results. Phase 1A, known as the R ampersand D phase, was developed to allow each vendor an opportunity to optimize and improve on their baseline process in terms of both cost and manufacturability. In this phase, multifilament billets were designed to explore several key variables such as alternate alloy sources, process modifications and improved billet designs. At the end of Phase 1, the results from both 1A and 1B were evaluated at a review between the SSCL and each vendor, and a final Phase 2 process was generated and fixed using the best results. In Phase 2, each vendor is required to manufacture roughly 6000 kg of superconducting cable under a firm fixed price contract which can then be used to create an accurate price estimate for competitive bidding on the full rate production CDM and CQM contracts. At the end of Phase 2, each vendor must meet the minimum requirements outlined in the contract to become a qualified superconducting cable supplier. For one requirement, critical process variables identified by the SSCL Conductor Department at the beginning of the VQP will be evaluated to determine the quality and uniformity of the material produced during Phase 2 of the program

  5. Seroprevalence of Dengue Fever in US Army Special Operations Forces: Initial Results and the Way Ahead.

    Science.gov (United States)

    Caci, Jennifer B; Blaylock, Jason M; De La Barrera, Rafael; Griggs, April N; Lin, Leyi; Jarman, Richard G; Thomas, Stephen J; Lyons, Arthur G

    2014-01-01

    The endemicity of dengue fever (DF) and, consequently, sequelae of DF are increasing worldwide. The increases are largely a result of widespread international travel and the increased range of the mosquito vectors. US Army Special Operations Command (USASOC) personnel are at an increased risk of exposure to dengue based on their frequent deployments to and presence in dengue endemic areas worldwide. Repeated deployments to different endemic areas can increase the risk for developing the more serious sequelae of dengue: dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Information about the seroprevalence rate of dengue in USASOC personnel, in particular, is lacking and is critical to assessing the risk, tailoring preventive medicine countermeasures, leveraging field diagnostics, and maintaining mission capability. In the first part of a two-part project to assess baseline seroprevalence in USASOC units, a random, unit-stratified sample of 500 anonymous serum specimens from personnel assigned to the highest-risk units in USASOC were screened for dengue using a microneutralization assay. Of the 500 specimens screened, 56 (11.2%) of 500 had neutralizing titers (NT) (MN₅₀≥10) against at least one DENV serotype. Subsequent sample titration resulted in 48 (85.7%) of 56 of the samples with NT (MN₅₀≥10) against at least one dengue serotype for an overall dengue exposure rate of 9.6% (48 of 500). The second part of the ongoing project, started in 2012, was a multicenter, serosurveillance project using predeployment and postdeployment sera collected from USASOC personnel deployed to South and Central America, Africa, and Southeast Asia. Preliminary results show a 13.2% (55 of 414) seropositivity rate. The significance of these findings as they relate to personal risk and operational impact is discussed. 2014.

  6. Initial results from 3D-DDTC detectors on p-type substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zoboli, A., E-mail: zoboli@disi.unitn.i [Dipartimento di Ingegneria e Scienza dell' Informazione, Universita di Trento, and INFN, Sezione di Padova (Gruppo Collegato di Trento), Via Sommarive, 14, I-38100 Povo di Trento (Italy); Boscardin, M. [Fondazione Bruno Kessler, Centro per i Materiali e i Microsistemi, Via Sommarive, 18, I-38100 Povo di Trento (Italy); Bosisio, L. [Dipartimento di Fisica, Universita di Trieste, and INFN, Sezione di Trieste, Via A. Valerio, 2, I-34127 Trieste (Italy); Dalla Betta, G.-F. [Dipartimento di Ingegneria e Scienza dell' Informazione, Universita di Trento, and INFN, Sezione di Padova (Gruppo Collegato di Trento), Via Sommarive, 14, I-38100 Povo di Trento (Italy); Piemonte, C.; Ronchin, S.; Zorzi, N. [Fondazione Bruno Kessler, Centro per i Materiali e i Microsistemi, Via Sommarive, 18, I-38100 Povo di Trento (Italy)

    2010-01-11

    Owing to their superior radiation hardness compared to planar detectors, 3D detectors are one of the most promising technologies for the LHC upgrade foreseen in 2017. Fondazione Bruno Kessler has developed 3D Double-side Double-Type Column (3D-DDTC) detectors providing a technological simplifications with respect to a standard 3D process while aiming at comparable detector performance. We present selected results from the electrical characterization of 3D-DDTC structures from the second batch made on p-type substrates, supported also by TCAD simulations.

  7. Initial results with time series forecasting of TJ-II heliac waveforms

    International Nuclear Information System (INIS)

    Farias, G.; Dormido-Canto, S.; Vega, J.; Díaz, N.

    2015-01-01

    This article discusses about how to apply forecasting techniques to predict future samples of plasma signals during a discharge. One application of the forecasting could be to detect in real time anomalous behaviors in fusion waveforms. The work describes the implementation of three prediction techniques; two of them based on machine learning methods such as artificial neural networks and support vector machines for regression. The results have shown that depending on the temporal horizon, the predictions match the real samples in most cases with an error less than 5%, even more the forecasting of five samples ahead can reach accuracy over 90% in most signals analyzed.

  8. Comb-push ultrasound shear elastography of breast masses: initial results show promise.

    Science.gov (United States)

    Denis, Max; Mehrmohammadi, Mohammad; Song, Pengfei; Meixner, Duane D; Fazzio, Robert T; Pruthi, Sandhya; Whaley, Dana H; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

    2015-01-01

    To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

  9. Comb-push ultrasound shear elastography of breast masses: initial results show promise.

    Directory of Open Access Journals (Sweden)

    Max Denis

    Full Text Available To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE for classification of breast masses.CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results.Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s in comparison to benign masses (3.65 ± 1.36 m/s. Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC, the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC.CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

  10. Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

    International Nuclear Information System (INIS)

    Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

    2012-01-01

    High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl 2 ), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl 2 supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl 2 supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl 2 supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl 2 for 15 days along with training. ► CoCl 2 supplementation

  11. Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Kumar Anil

    2010-10-01

    Full Text Available Abstract Background The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6 plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. Results We have shown that RGCs exposed to hypoxia (1% or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM, revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Conclusion Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.

  12. Chronic hypoxia promotes pulmonary artery endothelial cell proliferation through H2O2-induced 5-lipoxygenase.

    Directory of Open Access Journals (Sweden)

    Kristi M Porter

    Full Text Available Pulmonary Hypertension (PH is a progressive disorder characterized by endothelial dysfunction and proliferation. Hypoxia induces PH by increasing vascular remodeling. A potential mediator in hypoxia-induced PH development is arachidonate 5-Lipoxygenase (ALOX5. While ALOX5 metabolites have been shown to promote pulmonary vasoconstriction and endothelial cell proliferation, the contribution of ALOX5 to hypoxia-induced proliferation remains unknown. We hypothesize that hypoxia exposure stimulates HPAEC proliferation by increasing ALOX5 expression and activity. To test this, human pulmonary artery endothelial cells (HPAEC were cultured under normoxic (21% O2 or hypoxic (1% O2 conditions for 24-, 48-, or 72 hours. In a subset of cells, the ALOX5 inhibitor, zileuton, or the 5-lipoxygenase activating protein inhibitor, MK-886, was administered during hypoxia exposure. ALOX5 expression was measured by qRT-PCR and western blot and HPAEC proliferation was assessed. Our results demonstrate that 24 and 48 hours of hypoxia exposure have no effect on HPAEC proliferation or ALOX5 expression. Seventy two hours of hypoxia significantly increases HPAEC ALOX5 expression, hydrogen peroxide (H2O2 release, and HPAEC proliferation. We also demonstrate that targeted ALOX5 gene silencing or inhibition of the ALOX5 pathway by pharmacological blockade attenuates hypoxia-induced HPAEC proliferation. Furthermore, our findings indicate that hypoxia-induced increases in cell proliferation and ALOX5 expression are dependent on H2O2 production, as administration of the antioxidant PEG-catalase blocks these effects and addition of H2O2 to HPAEC promotes proliferation. Overall, these studies indicate that hypoxia exposure induces HPAEC proliferation by activating the ALOX5 pathway via the generation of H2O2.

  13. Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro.

    Science.gov (United States)

    Sanna, K; Rofstad, E K

    1994-07-15

    Rodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX-c, COX-c, SAX-c, WIX-c) have been studied. Cells were exposed to hypoxia (O2 concentration WIX-c. BEX-c and SAX-c were sensitive to methotrexate without hypoxia pre-treatment, whereas COX-c and WIX-c were resistant initially. Hypoxia-induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.

  14. Crystal habit modification of nickel-ferrite: development and results of initial laboratory testing

    International Nuclear Information System (INIS)

    Anderson, C.E.; Varrin, R.D.; Marks, C.; Barkatt, A.; Kim, K.; Fruzzetti, K.P.

    2010-01-01

    This paper documents the results of a laboratory test program conducted to assess the feasibility of using a new type of additive in the primary coolant of pressurized water reactors (PWRs) or to boiling water reactor (BWR) coolant. These additives, known as crystal habit modifiers (CHMs), could potentially be used to control the crystal habits, or shapes, that comprise primary deposits and crud. Similar additives are used throughout the chemical process industry to produce products with desirable crystalline structure, morphology, density, particle size, or surface area. Based on the successes of CHM technologies in other industries, CHMs may have the potential to alleviate problems associated with deposits in nuclear plants including axial offset anomaly (AOA). By controlling the habit of deposit materials, it may be possible to retard deposit formation, produce deposits with desirable properties (e.g., high friability, low or high porosity), or promote a preferred chemical composition or deposit structure that is more amenable to removal. Desirable properties that could be selected for include enhanced boiling efficiency, reduced surface affinity for boron, and resistance to consolidation. The results of this project demonstrate that crystal habit modification of nickel ferrite, a typical primary side deposit species, can be achieved by the addition of both inorganic and organic chemical species (CHMs). The most significant habit modification of nickel ferrite was observed with the addition of metal species (e.g., Zn, Cr) due to their incorporation into the crystal lattice of the oxide. Lesser degrees of modification were achieved with organic additives such as acetate. Specific CHM candidates that may have a beneficial effect on PWR operation are identified in this paper. In addition, this paper summarizes the refinement of several methods for synthesizing nickel ferrites under hydrothermal conditions that may benefit those interested in studying crud and

  15. Crystal habit modification of nickel-ferrite: development and results of initial laboratory testing

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, C.E.; Varrin, R.D.; Marks, C. [Dominion Engineering, Inc., Reston, Virginia (United States); Barkatt, A. [The Catholic Univ. of America, Dept. of Chemistry, Washington, District of Columbia (United States); Kim, K.; Fruzzetti, K.P. [Electric Power Research Inst., Palo Alto, California (United States)

    2010-07-01

    This paper documents the results of a laboratory test program conducted to assess the feasibility of using a new type of additive in the primary coolant of pressurized water reactors (PWRs) or to boiling water reactor (BWR) coolant. These additives, known as crystal habit modifiers (CHMs), could potentially be used to control the crystal habits, or shapes, that comprise primary deposits and crud. Similar additives are used throughout the chemical process industry to produce products with desirable crystalline structure, morphology, density, particle size, or surface area. Based on the successes of CHM technologies in other industries, CHMs may have the potential to alleviate problems associated with deposits in nuclear plants including axial offset anomaly (AOA). By controlling the habit of deposit materials, it may be possible to retard deposit formation, produce deposits with desirable properties (e.g., high friability, low or high porosity), or promote a preferred chemical composition or deposit structure that is more amenable to removal. Desirable properties that could be selected for include enhanced boiling efficiency, reduced surface affinity for boron, and resistance to consolidation. The results of this project demonstrate that crystal habit modification of nickel ferrite, a typical primary side deposit species, can be achieved by the addition of both inorganic and organic chemical species (CHMs). The most significant habit modification of nickel ferrite was observed with the addition of metal species (e.g., Zn, Cr) due to their incorporation into the crystal lattice of the oxide. Lesser degrees of modification were achieved with organic additives such as acetate. Specific CHM candidates that may have a beneficial effect on PWR operation are identified in this paper. In addition, this paper summarizes the refinement of several methods for synthesizing nickel ferrites under hydrothermal conditions that may benefit those interested in studying crud and

  16. Tablets in Education. Results from the Initiative ETiE, for Teaching Plants to Primary School Students

    Science.gov (United States)

    Fokides, Emmanuel; Atsikpasi, Pinelopi

    2017-01-01

    The study presents the results from the first phase of the initiative Emerging Technologies in Education. At this stage, we examined the learning outcomes from the use of tablets and an application as content delivery methods for teaching plants' parts, reproduction types and organs, photosynthesis, and respiration. The project lasted for four…

  17. Initial Results on Neutralized Drift Compression Experiments (NDCX-IA) for High Intensity Ion Beam

    CERN Document Server

    Roy, Prabir K; Baca, David; Bieniosek, Frank; Coleman, Joshua E; Davidson, Ronald C; Efthimion, Philip; Eylon, Shmuel; Gilson, Erik P; Grant Logan, B; Greenway, Wayne; Henestroza, Enrique; Kaganovich, Igor D; Leitner, Matthaeus; Rose, David; Sefkow, Adam; Sharp, William M; Shuman, Derek; Thoma, Carsten H; Vanecek, David; Waldron, William; Welch, Dale; Yu, Simon

    2005-01-01

    Ion beam neutralization and compression experiments are designed to determine the feasibility of using compressed high intensity ion beams for high energy density physics (HEDP) experiments and for inertial fusion power. To quantitatively ascertain the various mechanisms and methods for beam compression, the Neutralized Drift Compression Experiment (NDCX) facility is being constructed at Lawrence Berkeley National Laboratory (LBNL). In the first compression experiment, a 260 KeV, 25 mA, K+ ion beam of centimeters size is radially compressed to a mm size spot by neutralization in a meter-long plasma column and beam peak current is longitudinally compressed by an induction velocity tilt core. Instrumentation, preliminary results of the experiments, and practical limits of compression are presented. These include parameters such as emittance, degree of neutralization, velocity tilt time profile, and accuracy of measurements (fast and spatially high resolution diagnostic) are discussed.

  18. Summary of initial results from the GSFC fluxgate magnetometer on Pioneer 11

    Science.gov (United States)

    Acuna, M. H.; Ness, N. F.

    1975-01-01

    The main magnetic field of Jupiter was measured by the Fluxgate Magnetometer on Pioneer 11 and analysis reveals it to be relatively more complex than expected. In a centered spherical harmonic representation with a maximum order of n = 3 (designated GSFC model 04), the dipole term (with opposite polarity to the Earth's) has a moment of 4.28 Gauss x (Jupiter radius cubed), tilted by 9.6 deg towards a system 111 longitude of 232. The quadrupole and octupole moments are significant, 24% and 21% of the dipole moment respectively, and this leads to deviations of the planetary magnetic field from a simple offset tilted dipole for distances smaller than three Jupiter radii. The GSFC model shows a north polar field strength of 14 Gauss and a south polar field strength of 10.4 Gauss. Enhanced absorption effects in the radiation belts may be predicted as a result of field distortion.

  19. Data processing and initial results of Chang'e-3 lunar penetrating radar

    Science.gov (United States)

    Su, Yan; Fang, Guang-You; Feng, Jian-Qing; Xing, Shu-Guo; Ji, Yi-Cai; Zhou, Bin; Gao, Yun-Ze; Li, Han; Dai, Shun; Xiao, Yuan; Li, Chun-Lai

    2014-12-01

    To improve our understanding of the formation and evolution of the Moon, one of the payloads onboard the Chang'e-3 (CE-3) rover is Lunar Penetrating Radar (LPR). This investigation is the first attempt to explore the lunar subsurface structure by using ground penetrating radar with high resolution. We have probed the subsurface to a depth of several hundred meters using LPR. In-orbit testing, data processing and the preliminary results are presented. These observations have revealed the configuration of regolith where the thickness of regolith varies from about 4 m to 6 m. In addition, one layer of lunar rock, which is about 330 m deep and might have been accumulated during the depositional hiatus of mare basalts, was detected.

  20. Data processing and initial results of Chang'e-3 lunar penetrating radar

    International Nuclear Information System (INIS)

    Su Yan; Feng Jian-Qing; Xing Shu-Guo; Li Han; Dai Shun; Xiao Yuan; Li Chun-Lai; Fang Guang-You; Ji Yi-Cai; Zhou Bin; Gao Yun-Ze

    2014-01-01

    To improve our understanding of the formation and evolution of the Moon, one of the payloads onboard the Chang'e-3 (CE-3) rover is Lunar Penetrating Radar (LPR). This investigation is the first attempt to explore the lunar subsurface structure by using ground penetrating radar with high resolution. We have probed the subsurface to a depth of several hundred meters using LPR. In-orbit testing, data processing and the preliminary results are presented. These observations have revealed the configuration of regolith where the thickness of regolith varies from about 4 m to 6 m. In addition, one layer of lunar rock, which is about 330 m deep and might have been accumulated during the depositional hiatus of mare basalts, was detected

  1. Using Empirical Data to Estimate Potential Functions in Commodity Markets: Some Initial Results

    Science.gov (United States)

    Shen, C.; Haven, E.

    2017-12-01

    This paper focuses on estimating real and quantum potentials from financial commodities. The log returns of six common commodities are considered. We find that some phenomena, such as the vertical potential walls and the time scale issue of the variation on returns, also exists in commodity markets. By comparing the quantum and classical potentials, we attempt to demonstrate that the information within these two types of potentials is different. We believe this empirical result is consistent with the theoretical assumption that quantum potentials (when embedded into social science contexts) may contain some social cognitive or market psychological information, while classical potentials mainly reflect `hard' market conditions. We also compare the two potential forces and explore their relationship by simply estimating the Pearson correlation between them. The Medium or weak interaction effect may indicate that the cognitive system among traders may be affected by those `hard' market conditions.

  2. Byggmeister Test Home: Analysis and Initial Results of Cold Climate Wood-Framed Home Retrofit

    Energy Technology Data Exchange (ETDEWEB)

    Gates, C.

    2013-01-01

    BSC seeks to further the energy efficiency market for New England area retrofit projects by supporting projects that are based on solid building science fundamentals and verified implementation. With the high exposure of energy efficiency and retrofit terminology being used in the general media at this time, it is important to have evidence that measures being proposed will in fact benefit the homeowner through a combination of energy savings, improved durability, and occupant comfort. There are several basic areas of research to which the technical report for these test homes can be expected to contribute. These include the combination of measures that is feasible, affordable and acceptable to homeowners as well as expectations versus results. Two Byggmeister multi-family test homes in Massachusetts are examined with the goal of providing case studies that could be applied to other similar New England homes.

  3. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Kjel [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: kjel_andersen@web.de; Hennersdorf, Marcus [Department of Cardiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: hennersdorf@med.uni-duesseldorf.de; Cohnen, Mathias [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: cohnen@med.uni-duesseldorf.de; Blondin, Dirk [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: blondin@med.uni-duesseldorf.de; Moedder, Ulrich [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: moedder@uni-duesseldorf.de; Poll, Ludger W. [Institute of Diagnostic Radiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf (Germany)], E-mail: poll@gmx.de

    2009-07-15

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  4. Initial experience with fecal microbiota transplantation in Clostridium difficile infection: transplant protocol and preliminary results

    Directory of Open Access Journals (Sweden)

    Ana Ponte

    2015-07-01

    Full Text Available Background and aims: Clostridium difficile infection (CDI constitutes an important cause of antibiotic-associated diarrhea. Recurrence after first-line treatment with antibiotics is high and fecal microbiota transplantation (FMT may be effective for refractory and recurrent CDI. This series aims to describe the efficacy of FMT in the treatment of refractory and recurrent CDI. Methods: A prospectively recorded single-centre case series of patients with persistent or recurrent CDI treated with FMT between June 2014 and March 2015 was analyzed. Primary and secondary outcomes were defined as resolution of diarrhea without recurrence of CDI within 2 months after one or more FMT, respectively. A descriptive analysis was performed. Results: 8 FMT were performed in 6 patients, 3 with refractory CDI and 3 with recurrent CDI. The median age of recipients was 71 years and 66.7% were women. One FMT was delivered through colonoscopy and the remaining 87.5% through esophagogastroduodenoscopy. One upper FMT was excluded due to recurrence of CDI after antibiotic exposure for a respiratory infection. The overall cure rate of FMT was total with lower route and 83.3% with upper route. Primary cure rate was achieved in 83.3% of patients and secondary cure rate was achieved in all patients. Median time to resolution of diarrhea after FMT was 1 day and no complications were reported during follow-up. Conclusion: FMT appears to constitute a safe and effective approach in the management of refractory and recurrent CDI. Difference between primary and secondary cure rates may result of insufficient restoration of intestinal microbiota with a single FMT.

  5. Lunar Reconnaissance Orbiter K-Band (26 GHz) Signal Analysis: Initial Study Results

    Science.gov (United States)

    Morabito, D. D.; Heckman, D.

    2017-11-01

    Lower frequency telemetry bands are becoming more limited in bandwidth due to increased competition between flight projects and other entities. Higher frequency bands offer significantly more bandwidth and hence the prospect of much higher data rates. Future or prospective flight projects considering higher frequency bands such as Ka-band (32 GHz) for deep-space and K-band (26 GHz) for near-Earth telemetry links are interested in past flight experience with available received data at these frequencies. Given that there is increased degradation due to the atmosphere at these higher frequencies, there is an effort to retrieve flight data of received signal strength to analyze performance under a variety of factors. Such factors include elevation angle, season, and atmospheric conditions. This article reports on the analysis findings of over 10 million observations of received signal strength of the Lunar Reconnaissance Orbiter (LRO) spacecraft collected between 2014 and 2017. We analyzed these data to characterize link performance over a wide range of weather conditions, season, and as a function of elevation angle. Based on this analysis, we have confirmed the safety of using a 3-dB margin for preflight planning purposes. These results suggest that a 3-dB margin with respect to adverse conditions will ensure a 98 to 99 percent data return under 95 percent weather conditions at 26 GHz (K-band), thus confirming expectations from link budget predictions. The results suggest that this margin should be applicable for all elevation angles above 10 deg. Thus, missions that have sufficient power for their desired data rates may opt to use 10 deg as their minimum elevation angle. Limitations of this study include climate variability and the fact that the observations require removal of hotbody noise in order to perform an adequate cumulative distribution function (CDF) analysis, which is planned for a future comprehensive study. Flight projects may use other link margins

  6. Initial Continuous Chemistry Results From The Roosevelt Island Ice Core (RICE)

    Science.gov (United States)

    Kjær, H. A.; Vallelonga, P. T.; Simonsen, M. F.; Neff, P. D.; Bertler, N. A. N.; Svensson, A.; Dahl-Jensen, D.

    2014-12-01

    The Roosevelt Island ice core (79.36° S, -161.71° W) was drilled in 2011-13 at the top of the Roosevelt Island ice dome, a location surrounded by the Ross ice shelf. The RICE ice core provides a unique opportunity to look into the past evolution of the West Antarctic Ice sheet. Further the site has high accumulation; 0.26 m of ice equivalent is deposited annually allowing annual layer determination for many chemical parameters. The RICE core was drilled to bedrock and has a total length of 763 metres. Preliminary results derived from water isotopes suggest that the oldest ice reaches back to the Eemian, with the last glacial being compressed in the bottom 60 metres. We present preliminary results from the RICE ice core including continuous measurements of acidity using an optical dye method, insoluble dust particles, conductivity and calcium. The core was analyzed at the New Zealand National Ice Core Research Facility at GNS Science in Wellington. The analytical set up used to determine climate proxies in the ice core was a modified version of the Copenhagen CFA system (Bigler et al., 2011). Key volcanic layers have been matched to those from the WAIS record (Sigl et al., 2013). A significant anti-correlation between acidity and calcium was seen in the Holocene part of the record. Due to the proximity to the ocean a large fraction of the calcium originates from sea salt and is in phase with total conductivity and sodium. In combination with the insoluble dust record, calcium has been apportioned into ocean-related and dust-related sources. Variability over the Holocene is presented and attributed to changing inputs of marine and dust aerosols.

  7. Myocardial delayed contrast enhancement in patients with arterial hypertension: Initial results of cardiac MRI

    International Nuclear Information System (INIS)

    Andersen, Kjel; Hennersdorf, Marcus; Cohnen, Mathias; Blondin, Dirk; Moedder, Ulrich; Poll, Ludger W.

    2009-01-01

    Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

  8. Imaging of patients with hippocampal sclerosis at 7 Tesla: initial results.

    Science.gov (United States)

    Breyer, Tobias; Wanke, Isabel; Maderwald, Stefan; Woermann, Friedrich G; Kraff, Oliver; Theysohn, Jens M; Ebner, Alois; Forsting, Michael; Ladd, Mark E; Schlamann, Marc

    2010-04-01

    Focal epilepsies potentially can be cured by neurosurgery; other treatment options usually remain symptomatic. High-resolution magnetic resonance (MR) imaging is the central imaging strategy in the evaluation of focal epilepsy. The most common substrate of temporal epilepsies is hippocampal sclerosis (HS), which cannot always be sufficiently characterized with current MR field strengths. Therefore, the purpose of our study was to demonstrate the feasibility of high-resolution MR imaging at 7 Tesla in patients with focal epilepsy resulting from a HS and to improve image resolution at 7 Tesla in patients with HS. Six patients with known HS were investigated with T1-, T2-, T2(*)-, and fluid-attenuated inversion recovery-weighted sequences at 7 Tesla with an eight-channel transmit-receive head coil. Total imaging time did not exceed 90 minutes per patient. High-resolution imaging at 7 Tesla is feasible and reveals high resolution of intrahippocampal structures in vivo. HS was confirmed in all patients. The maximum non-interpolated in-plane resolution reached 0.2 x 0.2 mm(2) in T2(*)-weighted images. The increased susceptibility effects at 7 Tesla revealed identification of intrahippocampal structures in more detail than at 1.5 Tesla, but otherwise led to stronger artifacts. Imaging revealed regional differences in hippocampal atrophy between patients. The scan volume was limited because of specific absorption rate restrictions, scanning time was reasonable. High-resolution imaging at 7 Tesla is promising in presurgical epilepsy imaging. "New" contrasts may further improve detection of even very small intrahippocampal structural changes. Therefore, further investigations will be necessary to demonstrate the potential benefit for presurgical selection of patients with various lesion patterns in mesial temporal epilepsies resulting from a unilateral HS. Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.

  9. Adjustments in cholinergic, adrenergic and purinergic control of cardiovascular function in snapping turtle embryos (Chelydra serpentina) incubated in chronic hypoxia.

    Science.gov (United States)

    Eme, John; Rhen, Turk; Crossley, Dane A

    2014-10-01

    Adenosine is an endogenous nucleoside that acts via G-protein coupled receptors. In vertebrates, arterial or venous adenosine injection causes a rapid and large bradycardia through atrioventricular node block, a response mediated by adenosine receptors that inhibit adenylate cyclase and decrease cyclic AMP concentration. Chronic developmental hypoxia has been shown to alter cardioregulatory mechanisms in reptile embryos, but adenosine's role in mediating these responses is not known. We incubated snapping turtle embryos under chronic normoxic (N21; 21 % O2) or chronic hypoxic conditions (H10; 10 % O2) beginning at 20 % of embryonic incubation. H10 embryos at 90 % of incubation were hypotensive relative to N21 embryos in both normoxic and hypoxic conditions. Hypoxia caused a hypotensive bradycardia in both N21 and H10 embryos during the initial 30 min of exposure; however, f H and P m both trended towards increasing during the subsequent 30 min, and H10 embryos were tachycardic relative to N21 embryos in hypoxia. Following serial ≥1 h exposure to normoxic and hypoxic conditions, a single injection of adenosine (1 mg kg(-1)) was given. N21 and H10 embryos responded to adenosine injection with a rapid and large hypotensive bradycardia in both normoxia and hypoxia. Gene expression for adenosine receptors were quantified in cardiac tissue, and Adora1 mRNA was the predominant receptor subtype with transcript levels 30-82-fold higher than Adora2A or Adora2B. At 70 % of incubation, H10 embryos had lower Adora1 and Adora2B expression compared to N21 embryos. Expression of Adora1 and Adora2B decreased in N21 embryos during development and did not differ from H10 embryos at 90 % of incubation. Similar to previous results in normoxia, H10 embryos in hypoxia were chronically tachycardic compared to N21 embryos before and after complete cholinergic and adrenergic blockade. Chronic hypoxia altered the development of normal cholinergic and adrenergic tone, as well as

  10. Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

    Directory of Open Access Journals (Sweden)

    Brita Singers Sørensen

    Full Text Available The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect, which weakens the spatial linkage between hypoxia and acidosis.Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15 were treated with hypoxia, acidosis (pH 6.3, or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein.Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe, genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2, and Ribosomal protein L37 (RPL37. Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa and protein synthesis (both cell lines was observed when hypoxia and low pHe were combined.We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de

  11. Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

    Science.gov (United States)

    Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R; Alsner, Jan

    2015-01-01

    The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo

  12. Experimental warming delays autumn senescence in a boreal spruce bog: Initial results from the SPRUCE experiment

    Science.gov (United States)

    Richardson, Andrew; Furze, Morgan; Aubrecht, Donald; Milliman, Thomas; Nettles, Robert; Krassovski, Misha; Hanson, Paul

    2016-04-01

    August through December. These patterns can also be seen in other daily images recorded at the site since January 2012. Air warming treatments at SPRUCE began in August 2015, and had a substantial influence on autumn senescence of the plant community, as a whole, within each chamber. Generally, vegetation in the warmed chambers stayed green longer than that in the unwarmed chambers. We characterized the seasonality by fitting a sigmoid curve to the Gcc time series data, and we used the autumn half-maximum date of the sigmoid as an indicator of the timing of senescence. We found a strong linear relationship between senescence date and temperature treatment (r2 = 0.71,n = 10). Overall, senescence was delayed by 3.5 ± 0.7 days per 1° C of warming. Thus, although photoperiod is widely believed to be the key trigger for autumn senescence, our results do not indicate that the autumn response to warming is in any way constrained by day length. The SPRUCE experiment is planned to running through 2025. Looking forward, we anticipate that different results may be obtained in year 2 of the SPRUCE experiment if warming treatments result in earlier spring onset, and increased evapotranspiration during spring and early summer, leading to drought conditions by late summer.

  13. [The department budget, in the context of the hospital global budget. Initial results in general medicine].

    Science.gov (United States)

    Besançon, F

    1984-02-23

    In a general hospital (Hôtel-Dieu, in the center of Paris), run with a global budget, budgets determined for each unit were introduced as an experiment in 1980. Physicians were in charge of certain expenses, mainly: linen, drugs, transportation of patients to and from other hospitals within Paris, and blood fractions. The whole does not exceed 4% of the turnover (FF 20 millions in 1980) of a 67 bed internal medicine unit. Other accounts deal with the stays, admissions, prescriptions of technical acts, laboratory analyses, and X-rays. In 1980, expenses were 11% more than budgeted, but the increase in stays and particularly in admissions was significantly greater. The resulting savings were 8.8% and 18.7% for stays and admissions respectively. Psychic reactions were variable. The subsequent budgets followed the fluctuations of recorded expenses, which were fairly important in both directions. The unit budget may be an advance or a regression, in a restrictive and past-perpetuating context. The coherence between the unit budget and the global hospital budget is questionable. Physicians were willing to take part in accounting and saving. They have good reason for not enlarging their financial responsibilities. Conversely, they may give more attention to diseases of public opinion.

  14. Quantification of renal allograft perfusion using arterial spin labeling MRI: initial results.

    Science.gov (United States)

    Lanzman, Rotem S; Wittsack, Hans-Jörg; Martirosian, Petros; Zgoura, Panagiota; Bilk, Philip; Kröpil, Patric; Schick, Fritz; Voiculescu, Adina; Blondin, Dirk

    2010-06-01

    To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging. Following approval of the local ethics committee, 20 renal allograft recipients were included in this study. ASL perfusion measurement and an anatomical T2-weighted single-shot fast spin-echo (HASTE) sequence were performed on a 1.5-T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). T2-weighted MR urography was performed in patients with suspected ureteral obstruction. Patients were assigned to three groups: group a, 6 patients with stable allograft function over the previous 4 months; group b, 7 patients with good allograft function who underwent transplantation during the previous 3 weeks; group c, 7 allograft recipients with an acute deterioration of renal function. Mean cortical perfusion values were 304.8 +/- 34.4, 296.5 +/- 44.1, and 181.9 +/- 53.4 mg/100 ml/min for groups a, b and c, respectively. Reduction in cortical perfusion in group c was statistically significant. Our results indicate that ASL is a promising technique for nonenhanced quantification of cortical perfusion of renal allografts. Further studies are required to determine the clinical value of ASL for monitoring renal allograft recipients.

  15. Initial communication survey results for the Hanford Environmental Dose Reconstruction Project

    International Nuclear Information System (INIS)

    Beck, D.M.

    1991-03-01

    To support the public communication efforts of the Technical Steering Panel of the Hanford Environmental Dose Reconstruction (HEDR) Project, a public survey was conducted. The survey was intended to provide information about the public's knowledge and interest in the project and the best ways to communicate project results. Questions about the project were included as part of an omnibus survey conducted by Washington State University. The survey was conducted by phone to Washington State residents in the spring of 1990. This report gives the HEDR-related questions and summary data of responses. Questions associated with the HEDR Project were grouped into four categories: knowledge of the HEDR Project; interest in the project; preferred ways of receiving information about the project (including public information meetings, a newsletter mailed to homes, presentations to civic groups in the respondent's community, a computer bulletin board respondent could access with a modem, information displays at public buildings and shopping malls, and an information video sent to respondent); and level of concern over past exposure from Hanford operations. Questions abut whom state residents are most likely to trust about radiation issues were also part of the omnibus survey, and responses are included in this report

  16. Resonant Frequency Control For the PIP-II Injector Test RFQ: Control Framework and Initial Results

    Energy Technology Data Exchange (ETDEWEB)

    Edelen, A. L. [Colorado State U.; Biedron, S. G.; Milton, S. V.; Bowring, D.; Chase, B. E.; Edelen, J. P.; Nicklaus, D.; Steimel, J.

    2016-12-16

    For the PIP-II Injector Test (PI-Test) at Fermilab, a four-vane radio frequency quadrupole (RFQ) is designed to accelerate a 30-keV, 1-mA to 10-mA, H- beam to 2.1 MeV under both pulsed and continuous wave (CW) RF operation. The available headroom of the RF amplifiers limits the maximum allowable detuning to 3 kHz, and the detuning is controlled entirely via thermal regulation. Fine control over the detuning, minimal manual intervention, and fast trip recovery is desired. In addition, having active control over both the walls and vanes provides a wider tuning range. For this, we intend to use model predictive control (MPC). To facilitate these objectives, we developed a dedicated control framework that handles higher-level system decisions as well as executes control calculations. It is written in Python in a modular fashion for easy adjustments, readability, and portability. Here we describe the framework and present the first control results for the PI-Test RFQ under pulsed and CW operation.

  17. Quantification of renal allograft perfusion using arterial spin labeling MRI: initial results

    International Nuclear Information System (INIS)

    Lanzman, Rotem S.; Wittsack, Hans-Joerg; Bilk, Philip; Kroepil, Patric; Blondin, Dirk; Martirosian, Petros; Schick, Fritz; Zgoura, Panagiota; Voiculescu, Adina

    2010-01-01

    To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging. Following approval of the local ethics committee, 20 renal allograft recipients were included in this study. ASL perfusion measurement and an anatomical T2-weighted single-shot fast spin-echo (HASTE) sequence were performed on a 1.5-T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). T2-weighted MR urography was performed in patients with suspected ureteral obstruction. Patients were assigned to three groups: group a, 6 patients with stable allograft function over the previous 4 months; group b, 7 patients with good allograft function who underwent transplantation during the previous 3 weeks; group c, 7 allograft recipients with an acute deterioration of renal function. Mean cortical perfusion values were 304.8 ± 34.4, 296.5 ± 44.1, and 181.9 ± 53.4 mg/100 ml/min for groups a, b and c, respectively. Reduction in cortical perfusion in group c was statistically significant. Our results indicate that ASL is a promising technique for nonenhanced quantification of cortical perfusion of renal allografts. Further studies are required to determine the clinical value of ASL for monitoring renal allograft recipients. (orig.)

  18. A web application for moderation training: Initial results of a randomized clinical trial1

    Science.gov (United States)

    Hester, Reid K.; Delaney, Harold D.; Campbell, William; Handmaker, Nancy

    2009-01-01

    Eighty four heavy drinkers who responded to a newspaper recruitment ad were randomly assigned to receive either: a) training in a moderate drinking protocol via an Internet-based program (www.moderatedrinking.com) and use of the online resources of Moderation Management (MM) (www.moderation.org) or b) use of the online resources of MM alone. Follow-ups are being conducted at 3, 6, and 12 months. Results of the recently completed 3 month follow-up (86% follow-up) indicated both groups significantly reduced their drinking based on these variables: standard drinks per week; percent days abstinent; and mean BAC per drinking day. Both groups also significantly reduced their alcohol-related problems. Relative to the control group the experimental group had better outcomes on percent days abstinent and log Drinks per Drinking Day. These short-term outcome data provide evidence for the effectiveness of both the moderate drinking web application and of the resources available online at MM in helping heavy drinkers reduce their drinking and alcohol-related problems. PMID:19339137

  19. Initial results from a prototype whole-body photon-counting computed tomography system.

    Science.gov (United States)

    Yu, Z; Leng, S; Jorgensen, S M; Li, Z; Gutjahr, R; Chen, B; Duan, X; Halaweish, A F; Yu, L; Ritman, E L; McCollough, C H

    X-ray computed tomography (CT) with energy-discriminating capabilities presents exciting opportunities for increased dose efficiency and improved material decomposition analyses. However, due to constraints imposed by the inability of photon-counting detectors (PCD) to respond accurately at high photon flux, to date there has been no clinical application of PCD-CT. Recently, our lab installed a research prototype system consisting of two x-ray sources and two corresponding detectors, one using an energy-integrating detector (EID) and the other using a PCD. In this work, we report the first third-party evaluation of this prototype CT system using both phantoms and a cadaver head. The phantom studies demonstrated several promising characteristics of the PCD sub-system, including improved longitudinal spatial resolution and reduced beam hardening artifacts, relative to the EID sub-system. More importantly, we found that the PCD sub-system offers excellent pulse pileup control in cases of x-ray flux up to 550 mA at 140 kV, which corresponds to approximately 2.5×10 11 photons per cm 2 per second. In an anthropomorphic phantom and a cadaver head, the PCD sub-system provided image quality comparable to the EID sub-system for the same dose level. Our results demonstrate the potential of the prototype system to produce clinically-acceptable images in vivo .

  20. The Mediterranean Moored Multi-sensor Array (M3A: system development and initial results

    Directory of Open Access Journals (Sweden)

    K. Nittis

    Full Text Available Operational forecasting of ocean circulation and marine ecosystem fluctuations requires multi-parametric real-time measurements of physical and biochemical properties. The architecture of a system that is able to provide such measurements from the upper-thermocline layers of the Mediterranean Sea is described here. The system was developed for the needs of the Mediterranean Forecasting System and incorporates state-of-the-art sensors for optical and chemical measurements in the upper 100 m and physical measurements down to 500 m. Independent moorings that communicate via hydro-acoustic modems are hosting the sensors. The satellite data transfer and the large autonomy allow for the operation of the system in any open-ocean site. The system has been in pre-operational use in the Cretan Sea since January 2000. The results of this pilot phase indicate that multi-parametric real-time observations with the M3A system are feasible, if a consistent maintenance and re-calibration program is followed. The main limitations of the present configuration of M3A are related: (a to bio-fouling that primarily affects the turbidity and secondarily affects the other optical sensors, and (b to the limited throughput of the currently used satellite communication system.

    Key words. Atmospheric composition and structure (instruments and techniques. Oceanography: general (ocean prediction Oceanography: physical (upper ocean process

  1. Diffusion tensor imaging and tractography for assessment of renal allograft dysfunction - initial results

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, M.; Rodt, T.; Wacker, F.; Galanski, M.; Hartung, D. [Institute for Diagnostic and Interventional Radiology, Hannover Medical School - Germany, Hannover (Germany); Gwinner, W. [Clinic for Nephrology, Hannover Medical School - Germany, Hannover (Germany); Lehner, F. [Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School - Germany, Hannover (Germany)

    2011-11-15

    To evaluate MR diffusion tensor imaging (DTI) as non-invasive diagnostic tool for detection of acute and chronic allograft dysfunction and changes of organ microstructure. 15 kidney transplanted patients with allograft dysfunction and 14 healthy volunteers were examined using a fat-saturated echo-planar DTI-sequence at 1.5 T (6 diffusion directions, b = 0, 600 s/mm{sup 2}). Mean apparent diffusion coefficient (ADC) and mean fractional anisotropy (FA) were calculated separately for the cortex and for the medulla and compared between healthy and transplanted kidneys. Furthermore, the correlation between diffusion parameters and estimated GFR was determined. The ADC in the cortex and in the medulla were lower in transplanted than in healthy kidneys (p < 0.01). Differences were more distinct for FA, especially in the renal medulla, with a significant reduction in allografts (p < 0.001). Furthermore, in transplanted patients a correlation between mean FA in the medulla and estimated GFR was observed (r = 0.72, p < 0.01). Tractography visualized changes in renal microstructure in patients with impaired allograft function. Changes in allograft function and microstructure can be detected and quantified using DTI. However, to prove the value of DTI for standard clinical application especially correlation of imaging findings and biopsy results is necessary. (orig.)

  2. Initial results of the quality control in 11 computed tomography scanners at Curitiba

    International Nuclear Information System (INIS)

    Kodlulovich, S; Oliveira, L.; Jakubiak, R.R.; Miquelin, C.A.

    2008-01-01

    The aim of this study was to evaluate the image quality of 11 scanners installed in public and private centers of Curitiba, Brazil. This sample represents 30% of the CT scanners in the city so far. The ACR CT accreditation phantom was used to verify the accomplishment of the scanners performance to the international quality requirements. The results indicate that efforts should be concentrated in the maintenance of the equipments and specific training of the technicians. Most of the scanners have showed some non-conformity. In 27,5% of the sample the positioning requirement wasn't accomplished. The CT number accuracy evaluation showed that in 72,3 % of the scanners the CT numbers were out of the tolerance range, reaching values 35% greater than the limit. The low contrast resolution criteria weren't accomplished in 9% of the scanners. The main concern is that there isn't a specific program to evaluate the image quality of the CT scanners neither to estimate the CT doses in the procedures. (author)

  3. Longitudinal Study of the Impacts of a Climate Change Curriculum on Undergraduate Student Learning: Initial Results

    Directory of Open Access Journals (Sweden)

    Kristin C. Burkholder

    2017-05-01

    Full Text Available The present study assesses the efficacy of a semester-long undergraduate sustainability curriculum designed from a systems approach. The three-course curriculum, which incorporated environmental science and ethics courses along with an integrative course using a community-based learning pedagogy, was intended to provide students with experience using knowledge and skills from distinct disciplines in a holistic way in order to address the complex problems of the human acceptance of and response to anthropogenic climate change. In the fall of 2013, 23 of the 24 sophomore general education students enrolled in the three courses were surveyed at the beginning and end of the semester; 17 of those same students completed the survey again in the spring of 2016, their senior year. Results, which focus on the 17 students who continued to participate through their senior year, were analyzed with quantitative and qualitative methodologies. The pre/post data from the surveys demonstrated significant improvement in climate literacy, certainty, concern and urgency over the course of the semester; the senior data indicated that those improvements were largely retained. The study also suggests that the nine-credit curriculum improved transferable skills such as interdisciplinary thinking, self-confidence and public speaking. A qualitative analysis of three student cases, informed by a focus group (n = 7 of seniors along with other sources of information, suggested retention of such transferable skills, and, in some cases, deeper involvement in climate and sustainability action.

  4. The Mediterranean Moored Multi-sensor Array (M3A: system development and initial results

    Directory of Open Access Journals (Sweden)

    K. Nittis

    2003-01-01

    Full Text Available Operational forecasting of ocean circulation and marine ecosystem fluctuations requires multi-parametric real-time measurements of physical and biochemical properties. The architecture of a system that is able to provide such measurements from the upper-thermocline layers of the Mediterranean Sea is described here. The system was developed for the needs of the Mediterranean Forecasting System and incorporates state-of-the-art sensors for optical and chemical measurements in the upper 100 m and physical measurements down to 500 m. Independent moorings that communicate via hydro-acoustic modems are hosting the sensors. The satellite data transfer and the large autonomy allow for the operation of the system in any open-ocean site. The system has been in pre-operational use in the Cretan Sea since January 2000. The results of this pilot phase indicate that multi-parametric real-time observations with the M3A system are feasible, if a consistent maintenance and re-calibration program is followed. The main limitations of the present configuration of M3A are related: (a to bio-fouling that primarily affects the turbidity and secondarily affects the other optical sensors, and (b to the limited throughput of the currently used satellite communication system. Key words. Atmospheric composition and structure (instruments and techniques. Oceanography: general (ocean prediction Oceanography: physical (upper ocean process

  5. "Know Your Status": results from a novel, student-run HIV testing initiative on college campuses.

    Science.gov (United States)

    Milligan, Caitlin; Cuneo, C Nicholas; Rutstein, Sarah E; Hicks, Charles

    2014-08-01

    Know Your Status (KYS), a novel, student-run program offered free HIV-testing at a private university (PU) and community college (CC). Following completion of surveys of risk behaviors/reasons for seeking testing, students were provided with rapid, oral HIV-testing. We investigated testing history, risk behaviors, and HIV prevalence among students tested during the first three years of KYS. In total, 1408 tests were conducted, 5 were positive: 4/408 CC, 1/1000 PU (1% vs. 0.1%, p=0.01). Three positives were new diagnoses, all black men-who-have-sex-with-men (MSM). Over 50% of students were tested for the first time and 59% reported risk behaviors. CC students were less likely to have used condoms at last sex (a surrogate for risk behavior) compared to PU (OR 0.73, CI [0.54, 0.98]). Race, sexual identity, and sex were not associated with condom use. These results demonstrate that KYS successfully recruited large numbers of previously untested, at-risk students, highlighting the feasibility and importance of testing college populations.

  6. Quantitative analysis of pulmonary perfusion using time-resolved parallel 3D MRI - initial results

    International Nuclear Information System (INIS)

    Fink, C.; Buhmann, R.; Plathow, C.; Puderbach, M.; Kauczor, H.U.; Risse, F.; Ley, S.; Meyer, F.J.

    2004-01-01

    Purpose: to assess the use of time-resolved parallel 3D MRI for a quantitative analysis of pulmonary perfusion in patients with cardiopulmonary disease. Materials and methods: eight patients with pulmonary embolism or pulmonary hypertension were examined with a time-resolved 3D gradient echo pulse sequence with parallel imaging techniques (FLASH 3D, TE/TR: 0.8/1.9 ms; flip angle: 40 ; GRAPPA). A quantitative perfusion analysis based on indicator dilution theory was performed using a dedicated software. Results: patients with pulmonary embolism or chronic thromboembolic pulmonary hypertension revealed characteristic wedge-shaped perfusion defects at perfusion MRI. They were characterized by a decreased pulmonary blood flow (PBF) and pulmonary blood volume (PBV) and increased mean transit time (MTT). Patients with primary pulmonary hypertension or eisenmenger syndrome showed a more homogeneous perfusion pattern. The mean MTT of all patients was 3.3 - 4.7 s. The mean PBF and PBV showed a broader interindividual variation (PBF: 104-322 ml/100 ml/min; PBV: 8 - 21 ml/100 ml). Conclusion: time-resolved parallel 3D MRI allows at least a semi-quantitative assessment of lung perfusion. Future studies will have to assess the clinical value of this quantitative information for the diagnosis and management of cardiopulmonary disease. (orig.) [de

  7. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis

    NARCIS (Netherlands)

    Greijer, A.E.; Wall, E. van der

    2004-01-01

    Apoptosis can be induced in response to hypoxia. The severity of hypoxia determines whether cells become apoptotic or adapt to hypoxia and survive. A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic. Apoptosis regulatory

  8. Dual energy CT intracranial angiography: image quality, radiation dose and initial application results

    International Nuclear Information System (INIS)

    Chai Xue; Zhang Longjiang; Lu Guangming; Zhou Changsheng

    2009-01-01

    Objective: To assess the clinical value of dual-energy intracranial CT angiography (CTA). Methods: Forty-one patients suspected of intracranial vascular diseases underwent dual-energy intracranial CT angiography, and 41 patients who underwent conventional subtraction CT were enrolled as the control group. Image quality of intracranial and skull base vessels and radiation dose between dual-energy CTA and conventional subtraction CTA were compared using two independent sample nonparametric test and independent-samples t test, respectively. Prevalence and size of lesions detected by dual-energy CTA and digital subtraction CTA were compared using paired-samples t test and Spearman correlative analysis. Results: The percentage of image quality scored 5 was 70.7% (29/41) for dual-energy CTA and 75.6% (31/41) for conventional subtraction CTA. There was no significant difference between the two groups (Z= -0.455, P=0.650). Image quality of vessels at the skull base in conventional subtraction CTA was superior to that in dual-energy CTA, especially for the petrosal and syphon segment (Z=-4.087, P=0.000). Radiation exposure of dual energy CTA and conventional CTA were (396.54±17.43) and (1090.95±114.29) mGy·cm respectively. Radiation exposure was decreased by 64% (t=-38.52, P=0.000) by dual energy CTA compared with conventional subtraction CTA. Out of the 41 patients, 19 patients were diagnosed as intracranial aneurysm, 2 patients as arteriovenous malformation (AVM), 3 patients with Moya-moya's disease, and the remaining 17 patients with negative results. Nine patients with intracranial aneurysm, 2 patients with AVM, 3 patients with Moya-moya's disease, and 2 patients with negative findings underwent DSA or operation, with concordant findings from both techniques. Diameter of aneurysm neck, long axis and minor axis by dual-energy CTA was (2.90±1.61), (5.23±1.68) and (3.83±1.69) mm, respectively; Diameter of aneurysm neck, long axis and minor axis by DSA was (2.95±1

  9. Arterial spin labelling perfusion MRI of breast cancer using FAIR TrueFISP: Initial results

    International Nuclear Information System (INIS)

    Buchbender, S.; Obenauer, S.; Mohrmann, S.; Martirosian, P.; Buchbender, C.; Miese, F.R.; Wittsack, H.J.; Miekley, M.; Antoch, G.; Lanzman, R.S.

    2013-01-01

    Aim: To assess the feasibility of an unenhanced, flow-sensitive, alternating inversion recovery-balanced steady-state free precession (FAIR TrueFISP) arterial spin labelling (ASL) magnetic resonance imaging (MRI) technique for quantification of breast cancer perfusion. Materials and methods: Eighteen untreated breast tumour patients (mean age 53 ± 17 years, range 30–68 years) and four healthy controls (mean age 51 ± 14 years, range 33–68 years) were enrolled in this study and were imaged using a clinical 1.5 T MRI machine. Perfusion measurements were performed using a coronal single-section ASL FAIR TrueFISP technique in addition to a routine breast MRI examination. T1 relaxation time of normal breast parenchyma was determined in four healthy volunteers using the variable flip angle approach. The definitive diagnosis was obtained at histology after biopsy or surgery and was available for all patients. Results: ASL perfusion was successfully acquired in 13 of 18 tumour patients and in all healthy controls. The mean ASL perfusion of invasive ductal carcinoma tissue was significantly higher (88.2 ± 39.5 ml/100 g/min) compared to ASL perfusion of normal breast parenchyma (24.9 ± 12.7 ml/100 g/min; p < 0.05) and invasive lobular carcinoma (30.5 ± 4.3 ml/100 g/min; p < 0.05). No significant difference was found between the mean ASL perfusion of normal breast parenchyma and invasive lobular carcinoma tissue (p = 0.97). Conclusion: ASL MRI enables quantification of breast cancer perfusion without the use of contrast material. However, its impact on diagnosis and therapy management of breast tumours has to be evaluated in larger patient studies

  10. Plans for longitudinal and transverse neutralized beam compression experiments, and initial results from solenoid transport experiments

    International Nuclear Information System (INIS)

    Seidl, P.A.; Armijo, J.; Baca, D.; Bieniosek, F.M.; Coleman, J.; Davidson, R.C.; Efthimion, P.C.; Friedman, A.; Gilson, E.P.; Grote, D.; Haber, I.; Henestroza, E.; Kaganovich, I.; Leitner, M.; Logan, B.G.; Molvik, A.W.; Rose, D.V.; Roy, P.K.; Sefkow, A.B.; Sharp, W.M.; Vay, J.L.; Waldron, W.L.; Welch, D.R.; Yu, S.S.

    2007-01-01

    This paper presents plans for neutralized drift compression experiments, precursors to future target heating experiments. The target-physics objective is to study warm dense matter (WDM) using short-duration (∼1 ns) ion beams that enter the targets at energies just above that at which dE/dx is maximal. High intensity on target is to be achieved by a combination of longitudinal compression and transverse focusing. This work will build upon recent success in longitudinal compression, where the ion beam was compressed lengthwise by a factor of more than 50 by first applying a linear head-to-tail velocity tilt to the beam, and then allowing the beam to drift through a dense, neutralizing background plasma. Studies on a novel pulse line ion accelerator were also carried out. It is planned to demonstrate simultaneous transverse focusing and longitudinal compression in a series of future experiments, thereby achieving conditions suitable for future WDM target experiments. Future experiments may use solenoids for transverse focusing of un-neutralized ion beams during acceleration. Recent results are reported in the transport of a high-perveance heavy ion beam in a solenoid transport channel. The principal objectives of this solenoid transport experiment are to match and transport a space-charge-dominated ion beam, and to study associated electron-cloud and gas effects that may limit the beam quality in a solenoid transport system. Ideally, the beam will establish a Brillouin-flow condition (rotation at one-half the cyclotron frequency). Other mechanisms that potentially degrade beam quality are being studied, such as focusing-field aberrations, beam halo, and separation of lattice focusing elements

  11. Sequential Blood Filtration for Extracorporeal Circulation: Initial Results from a Proof-of-Concept Prototype

    Science.gov (United States)

    Herbst, Daniel P.

    2014-01-01

    Abstract: Micropore filters are used during extracorporeal circulation to prevent gaseous and solid particles from entering the patient’s systemic circulation. Although these devices improve patient safety, limitations in current designs have prompted the development of a new concept in micropore filtration. A prototype of the new design was made using 40-μm filter screens and compared against four commercially available filters for performance in pressure loss and gross air handling. Pre- and postfilter bubble counts for 5- and 10-mL bolus injections in an ex vivo test circuit were recorded using a Doppler ultrasound bubble counter. Statistical analysis of results for bubble volume reduction between test filters was performed with one-way repeated-measures analysis of variance using Bonferroni post hoc tests. Changes in filter performance with changes in microbubble load were also assessed with dependent t tests using the 5- and 10-mL bolus injections as the paired sample for each filter. Significance was set at p < .05. All filters in the test group were comparable in pressure loss performance, showing a range of 26–33 mmHg at a flow rate of 6 L/min. In gross air-handling studies, the prototype showed improved bubble volume reduction, reaching statistical significance with three of the four commercial filters. All test filters showed decreased performance in bubble volume reduction when the microbubble load was increased. Findings from this research support the underpinning theories of a sequential arterial-line filter design and suggest that improvements in microbubble filtration may be possible using this technique. PMID:26357790

  12. CT enteroclysis in the diagnosis of obscure gastrointestinal bleeding: initial results

    International Nuclear Information System (INIS)

    Jain, T.P.; Gulati, M.S.; Makharia, G.K.; Bandhu, S.; Garg, P.K.

    2007-01-01

    Aim: To evaluate the usefulness of computed tomography (CT) enteroclysis in patients with obscure gastrointestinal (GI) bleeding. Materials and methods: In a prospective study, CT enteroclysis was performed in 21 patients (median age 50 years; range 13-71 years) with obscure GI bleeding in which the source of the bleeding could not be detected despite the patient having undergone both upper GI endoscopic and colonoscopic examinations. The entire abdomen and pelvis was examined in the arterial and venous phases using multisection CT after distending the small intestine with 2 l of 0.5% methylcellulose as a neutral enteral contrast medium and the administration of 150 ml intravenous contrast medium. Results: Adequate distension of the small intestine was achieved in 20 of the 21 (95.2%) patients. Potential causes of GI bleeding were identified in 10 of the 21 (47.6%) patients using CT enteroclysis. The cause of the bleeding could be detected nine of 14 (64.3%) patients with overt, obscure GI bleeding. However, for patients with occult, obscure GI bleeding, the cause of the bleeding was identified in only one of the seven (14.3%) patients. The lesions identified by CT enteroclysis included small bowel tumours (n = 2), small bowel intussusceptions (n = 2), intestinal tuberculosis (n = 2), and vascular lesions (n = 3). All vascular lesions were seen equally well in both the arterial and venous phases. Conclusions: The success rate in detection of the cause of bleeding using CT enteroclysis was 47.6% in patients with obscure GI bleeding. The diagnostic yield was higher in patients with overt, obscure GI bleeding than in those with occult obscure GI bleeding

  13. Current discharge management of acute coronary syndromes: baseline results from a national quality improvement initiative.

    Science.gov (United States)

    Wai, A; Pulver, L K; Oliver, K; Thompson, A

    2012-05-01

    Evidence-practice gaps exist in the continuum of care for patients with acute coronary syndromes (ACS), particularly at hospital discharge. We aimed to describe the methodology and baseline results of the Discharge Management of Acute Coronary Syndromes (DMACS) project, focusing on the prescription of guideline-recommended medications, referral to cardiac rehabilitation and communication between the hospital, patient and their primary healthcare professionals. DMACS employed Drug Use Evaluation methodology involving data collection, evaluation and feedback, and targeted educational interventions. Adult patients with ACS discharged during a 4-month period were eligible to participate. Data were collected (maximum 50 patients) at each site through an inpatient medical record review, a general practitioner (GP) postal/fax survey conducted 14 days post discharge and a patient telephone survey 3 months post discharge. Forty-nine hospitals participated in the audit recruiting 1545 patients. At discharge, 57% of patients were prescribed a combination of antiplatelet agent(s), beta-blocker, statin and angiotensin-converting enzyme inhibitor and/or angiotensin II-antagonist. At 3 months post discharge, 48% of patients reported using the same combination. Some 67% of patients recalled being referred to cardiac rehabilitation; of these, 33% had completed the programme. In total, 83% of patients had a documented ACS management plan at discharge. Of these, 90% included a medication list, 56% a chest pain action plan and 54% risk factor modification advice. Overall, 65% of GPs rated the quality of information received in the discharge summary as 'very good' to 'excellent'. The findings of our baseline audit showed that despite the robust evidence base and availability of national guidelines, the management of patients with ACS can be improved. These findings will inform a multifaceted intervention strategy to improve adherence to guidelines for the discharge management of

  14. Initial quality performance results using a phantom to simulate chest computed radiography

    Directory of Open Access Journals (Sweden)

    Muhogora Wilbroad

    2011-01-01

    Full Text Available The aim of this study was to develop a homemade phantom for quantitative quality control in chest computed radiography (CR. The phantom was constructed from copper, aluminium, and polymenthylmethacrylate (PMMA plates as well as Styrofoam materials. Depending on combinations, the literature suggests that these materials can simulate the attenuation and scattering characteristics of lung, heart, and mediastinum. The lung, heart, and mediastinum regions were simulated by 10 mm x 10 mm x 0.5 mm, 10 mm x 10 mm x 0.5 mm and 10 mm x 10 mm x 1 mm copper plates, respectively. A test object of 100 mm x 100 mm and 0.2 mm thick copper was positioned to each region for CNR measurements. The phantom was exposed to x-rays generated by different tube potentials that covered settings in clinical use: 110-120 kVp (HVL=4.26-4.66 mm Al at a source image distance (SID of 180 cm. An approach similar to the recommended method in digital mammography was applied to determine the CNR values of phantom images produced by a Kodak CR 850A system with post-processing turned off. Subjective contrast-detail studies were also carried out by using images of Leeds TOR CDR test object acquired under similar exposure conditions as during CNR measurements. For clinical kVp conditions relevant to chest radiography, the CNR was highest over 90-100 kVp range. The CNR data correlated with the results of contrast detail observations. The values of clinical tube potentials at which CNR is the highest are regarded to be optimal kVp settings. The simplicity in phantom construction can offer easy implementation of related quality control program.

  15. Initial Results With Image-guided Cochlear Implant Programming in Children.

    Science.gov (United States)

    Noble, Jack H; Hedley-Williams, Andrea J; Sunderhaus, Linsey; Dawant, Benoit M; Labadie, Robert F; Camarata, Stephen M; Gifford, René H

    2016-02-01

    Image-guided cochlear implant (CI) programming can improve hearing outcomes for pediatric CI recipients. CIs have been highly successful for children with severe-to-profound hearing loss, offering potential for mainstreamed education and auditory-oral communication. Despite this, a significant number of recipients still experience poor speech understanding, language delay, and, even among the best performers, restoration to normal auditory fidelity is rare. Although significant research efforts have been devoted to improving stimulation strategies, few developments have led to significant hearing improvement over the past two decades. Recently introduced techniques for image-guided CI programming (IGCIP) permit creating patient-customized CI programs by making it possible, for the first time, to estimate the position of implanted CI electrodes relative to the nerves they stimulate using CT images. This approach permits identification of electrodes with high levels of stimulation overlap and to deactivate them from a patient's map. Previous studies have shown that IGCIP can significantly improve hearing outcomes for adults with CIs. The IGCIP technique was tested for 21 ears of 18 pediatric CI recipients. Participants had long-term experience with their CI (5 mo to 13 yr) and ranged in age from 5 to 17 years old. Speech understanding was assessed after approximately 4 weeks of experience with the IGCIP map. Using a two-tailed Wilcoxon signed-rank test, statistically significant improvement (p < 0.05) was observed for word and sentence recognition in quiet and noise, as well as pediatric self-reported quality-of-life (QOL) measures. Our results indicate that image guidance significantly improves hearing and QOL outcomes for pediatric CI recipients.

  16. Contrast-enhanced 3D MRI of lung perfusion in children with cystic fibrosis - initial results

    International Nuclear Information System (INIS)

    Eichinger, Monika; Puderbach, Michael; Zuna, Ivan; Kauczor, Hans-Ulrich; Fink, Christian; Gahr, Julie; Mueller, Frank-Michael; Ley, Sebastian; Plathow, Christian; Tuengerthal, Siegfried

    2006-01-01

    This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/α/ST: 600 ms/28 ms/180 /6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/α: 0.8/1.9 ms/40 ), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P<0.0001). Severe morphological changes led to perfusion defects (97%, P<0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients. (orig.)

  17. Multi-voxel MR spectroscopic imaging of the brain: utility in clinical setting-initial results

    International Nuclear Information System (INIS)

    Parmar, Hemant; Lim, Tchoyoson C.C.; Yin Hong; Chua, Violet; Khin, Lay-Wai; Raidy, Tom; Hui, Francis

    2005-01-01

    Background and purpose: Compared to single voxel methods, MR spectroscopic imaging (MRSI) of the brain provides metabolic information with improved anatomical coverage and spectral resolution, but may be difficult to perform in the clinical setting. We evaluate the factors influencing spectral quality in MRSI using a semi-automated method, focussing on lipid contamination, and phase correction errors related to magnetic field inhomogeneity. Methods: We retrospectively analysed MRSI studies planned by radiologists and radiographers. Two-dimensional MRSI studies using point-resolved spectroscopy (PRESS) localisation, at long echo time (135 or 144 ms) were acquired on a 1.5 T scanner. Studies that contained lipid contamination and abnormally inverted spectra were reviewed and the latter correlated with anatomic location at the base of skull, and with the area of the region of interest (ROI) studied. Results: Of 128 consecutive MRSI studies, six showed abnormal inverted spectra, of which four were acquired at the base of skull. Multivariate logistic regression analysis showed that study location at the base of skull, but not larger ROI, was a significant predictor for the risk of being affected by inverted spectra (RR for base of skull: 11.76, 95% CI: 1.86-74.18, P = 0.009. RR for area of ROI: 3.68, 95% CI: 0.57-23.67, P = 0.170). Seven studies showed lipid contamination; all were in close proximity to the overlying scalp. Conclusion: Using a semi-automated acquisition and post-processing method, MRSI can be successfully applied in the clinical setting. However, care should be taken to avoid regions of high magnetic field inhomogeneity at the base of skull, and lipid contamination in voxels prescribed near the scalp

  18. Field data collection of miscellaneous electrical loads in Northern California: Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Greenblatt, Jeffery B. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Pratt, Stacy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Willem, Henry [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Claybaugh, Erin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Desroches, Louis-Benoit [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Beraki, Bereket [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Nagaraju, Mythri [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Price, Sarah K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.; Young, Scott J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division. Energy Analysis and Environmental Impacts Dept.

    2013-02-25

    This report describes efforts to measure energy use of miscellaneous electrical loads (MELs) in 880 San Francisco Bay Area homes during the summer of 2012. Ten regions were selected for metering: Antioch, Berkeley, Fremont, Livermore, Marin County (San Rafael, Novato, Fairfax, and Mill Valley), Oakland/Emeryville, Pleasanton, Richmond, San Leandro, and Union City. The project focused on three major categories of devices: entertainment (game consoles, set-top boxes, televisions and video players), home office (computers, monitors and network equipment), and kitchen plug-loads (coffee/espresso makers, microwave ovens/toaster ovens/toasters, rice/slow cookers and wine chillers). These categories were important to meter because they either dominated the estimated overall energy use of MELs, are rapidly changing, or there are very little energy consumption data published. A total of 1,176 energy meters and 143 other sensors were deployed, and 90% of these meters and sensors were retrieved. After data cleaning, we obtained 711 valid device energy use measurements, which were used to estimate, for a number of device subcategories, the average time spent in high power, low power and “off” modes, the average energy use in each mode, and the average overall energy use. Consistent with observations made in previous studies, we find on average that information technology (IT) devices (home entertainment and home office equipment) consume more energy (15.0 and 13.0 W, respectively) than non-IT devices (kitchen plug-loads; 4.9 W). Opportunities for energy savings were identified in almost every device category, based on the time spent in various modes and/or the power levels consumed in those modes. Future reports will analyze the collected data in detail by device category and compare results to those obtained from prior studies.

  19. The Vermont oxford neonatal encephalopathy registry: rationale, methods, and initial results

    Science.gov (United States)

    2012-01-01

    Background In 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care. Methods Eligible infants were ≥ 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of ≤ 3, or receiving HT. Infants with central nervous system birth defects were excluded. Results From 2006–2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of ≤ 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived. Conclusions The VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice. PMID:22726296

  20. Assessment of pulmonary parenchyma perfusion with FAIR in comparison with DCE-MRI-Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Fan Li [Department of Radiology, ChangZheng Hospital Affiliated to Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003 (China)], E-mail: fanli0930@163.com; Liu Shiyuan [Department of Radiology, ChangZheng Hospital Affiliated to Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003 (China); Sun Fei [GE Healthcare China (China)], E-mail: Fei.sun@med.ge.com; Xiao Xiangsheng [Department of Radiology, ChangZheng Hospital Affiliated to Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003 (China)], E-mail: lizhaobin79@163.com

    2009-04-15

    Objective: The aim of this study was to assess pulmonary parenchyma perfusion with flow-sensitive alternating inversion recovery (FAIR) in comparison with 3D dynamic contrast-enhanced (DCE) imaging in healthy volunteers and in patients with pulmonary embolism or lung cancer. Materials and methods: Sixteen healthy volunteers and 16 patients with pulmonary embolism (5 cases) or lung cancer (11 cases) were included in this study. Firstly, the optimized inversion time of FAIR (TI) was determined in 12 healthy volunteers. Then, FAIR imaging with the optimized TI was performed followed by DCE-MRI on the other 4 healthy volunteers and 16 patients. Tagging efficiency of lung and SNR of perfusion images were calculated with different TI values. In the comparison of FAIR with DCE-MRI, the homogeneity of FAIR and DCE-MRI perfusion was assessed. In the cases of perfusion abnormality, the contrast between normal lung and perfusion defects was quantified by calculating a normalized signal intensity ratio. Results: One thousand milliseconds was the optimal TI, which generated the highest lung tagging efficiency and second highest PBF SNR. In the volunteers, the signal intensity of perfusion images acquired with both FAIR and DCE-MRI was homogeneous. Wedged-shaped or triangle perfusion defects were visualized in five pulmonary embolisms and three lung cancer cases. There was no significant statistical difference in signal intensity ratio between FAIR and DCE-MRI (P > 0.05). In the rest of eight lung cancers, all the lesions showed low perfusion against the higher perfused pulmonary parenchyma in both FAIR and DCE-MRI. Conclusion: Pulmonary parenchyma perfusion imaging with FAIR was feasible, consistent and could obtain similar functional information to that from DCE-MRI.

  1. Assessment of pulmonary parenchyma perfusion with FAIR in comparison with DCE-MRI-Initial results

    International Nuclear Information System (INIS)

    Fan Li; Liu Shiyuan; Sun Fei; Xiao Xiangsheng

    2009-01-01

    Objective: The aim of this study was to assess pulmonary parenchyma perfusion with flow-sensitive alternating inversion recovery (FAIR) in comparison with 3D dynamic contrast-enhanced (DCE) imaging in healthy volunteers and in patients with pulmonary embolism or lung cancer. Materials and methods: Sixteen healthy volunteers and 16 patients with pulmonary embolism (5 cases) or lung cancer (11 cases) were included in this study. Firstly, the optimized inversion time of FAIR (TI) was determined in 12 healthy volunteers. Then, FAIR imaging with the optimized TI was performed followed by DCE-MRI on the other 4 healthy volunteers and 16 patients. Tagging efficiency of lung and SNR of perfusion images were calculated with different TI values. In the comparison of FAIR with DCE-MRI, the homogeneity of FAIR and DCE-MRI perfusion was assessed. In the cases of perfusion abnormality, the contrast between normal lung and perfusion defects was quantified by calculating a normalized signal intensity ratio. Results: One thousand milliseconds was the optimal TI, which generated the highest lung tagging efficiency and second highest PBF SNR. In the volunteers, the signal intensity of perfusion images acquired with both FAIR and DCE-MRI was homogeneous. Wedged-shaped or triangle perfusion defects were visualized in five pulmonary embolisms and three lung cancer cases. There was no significant statistical difference in signal intensity ratio between FAIR and DCE-MRI (P > 0.05). In the rest of eight lung cancers, all the lesions showed low perfusion against the higher perfused pulmonary parenchyma in both FAIR and DCE-MRI. Conclusion: Pulmonary parenchyma perfusion imaging with FAIR was feasible, consistent and could obtain similar functional information to that from DCE-MRI.

  2. CT enteroclysis in the diagnosis of obscure gastrointestinal bleeding: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Jain, T.P. [Department ofRadiodiagnosis, All India Institute of Medical Sciences, New Delhi (India); Gulati, M.S. [Department of Imaging, Queen Elizabeth Hospital NHS Trust, London (United Kingdom); Makharia, G.K. [Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi (India)]. E-mail: govindmakharia@aiims.ac.in; Bandhu, S. [Department ofRadiodiagnosis, All India Institute of Medical Sciences, New Delhi (India); Garg, P.K. [Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi (India)

    2007-07-15

    Aim: To evaluate the usefulness of computed tomography (CT) enteroclysis in patients with obscure gastrointestinal (GI) bleeding. Materials and methods: In a prospective study, CT enteroclysis was performed in 21 patients (median age 50 years; range 13-71 years) with obscure GI bleeding in which the source of the bleeding could not be detected despite the patient having undergone both upper GI endoscopic and colonoscopic examinations. The entire abdomen and pelvis was examined in the arterial and venous phases using multisection CT after distending the small intestine with 2 l of 0.5% methylcellulose as a neutral enteral contrast medium and the administration of 150 ml intravenous contrast medium. Results: Adequate distension of the small intestine was achieved in 20 of the 21 (95.2%) patients. Potential causes of GI bleeding were identified in 10 of the 21 (47.6%) patients using CT enteroclysis. The cause of the bleeding could be detected nine of 14 (64.3%) patients with overt, obscure GI bleeding. However, for patients with occult, obscure GI bleeding, the cause of the bleeding was identified in only one of the seven (14.3%) patients. The lesions identified by CT enteroclysis included small bowel tumours (n = 2), small bowel intussusceptions (n = 2), intestinal tuberculosis (n = 2), and vascular lesions (n = 3). All vascular lesions were seen equally well in both the arterial and venous phases. Conclusions: The success rate in detection of the cause of bleeding using CT enteroclysis was 47.6% in patients with obscure GI bleeding. The diagnostic yield was higher in patients with overt, obscure GI bleeding than in those with occult obscure GI bleeding.

  3. Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet.

    Science.gov (United States)

    Anastasiou, Costas A; Yannakoulia, Mary; Kosmidis, Mary H; Dardiotis, Efthimios; Hadjigeorgiou, Giorgos M; Sakka, Paraskevi; Arampatzi, Xanthi; Bougea, Anastasia; Labropoulos, Ioannis; Scarmeas, Nikolaos

    2017-01-01

    strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption. Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.

  4. The Lunar Atmosphere and Dust Environment Explorer (LADEE): Initial Science Results

    Science.gov (United States)

    Elphic, R. C.; Hine, B.; Delory, G. T.; Salute, J. S.; Noble, S.; Colaprete, A.; Horanyi, M.; Mahaffy, P.

    2014-01-01

    On September 6, 2013, a near-perfect launch of the first Minotaur V rocket successfully carried NASA's Lunar Atmosphere and Dust Environment Explorer (LADEE) into a high-eccentricity geocentric orbit. LADEE arrived at the Moon on October 6, 2013, dur-ing the government shutdown. The spacecraft impact-ed the lunar surface on April 18, 2014, following a completely successful mission. LADEE's science objectives were twofold: (1) De-termine the composition and variability of the lunar atmosphere; (2) Characterize the lunar exospheric dust environment, and its variability. The LADEE science payload consisted of the Lunar Dust Experiment (LDEX), which sensed dust impacts in situ, for parti-cles between 100 nm and 5 micrometers; a neutral mass spectrometer (NMS), which sampled lunar exo-spheric gases in situ, over the 2-150 Dalton mass range; an ultraviolet/visible spectrometer (UVS) ac-quired spectra of atmospheric emissions and scattered light from tenuous dust, spanning a 250-800 nm wave-length range. UVS also performed dust extinction measurements via a separate solar viewer optic. The following are preliminary results for the lunar exosphere: (1) The helium exosphere of the Moon, first observed during Apollo, is clearly dominated by the delivery of solar wind He++. (2) Neon 20 is clearly seen as an important constituent of the exosphere. (3) Argon 40, also observed during Apollo and arising from interior outgassing, exhibits variations related to surface temperature-driven condensation and release, and is also enhanced over specific selenographic longi-tudes. (4) The sodium abundance varies with both lu-nar phase and with meteoroid influx, implicating both solar wind sputtering and impact vaporization process-es. (5) Potassium was also routinely monitored and exhibits some of the same properties as sodium. (6) Other candidate species were seen by both NMS and UVS, and await confirmation. Dust measurements have revealed a persistent "shroud" of small dust particles

  5. Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet.

    Directory of Open Access Journals (Sweden)

    Costas A Anastasiou

    associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption.Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.

  6. Features and Initial Results of the DIII-D Advanced Tokamak Radiative Divertor

    International Nuclear Information System (INIS)

    R.C. O'Neill; A.S. Bozek; M.E. Friend; C.B. Baxi; E.E. Reis; M.A. Mahdavi; D.G. Nilson; S.L. Allen; W.P. West

    1999-01-01

    into the designs of the structures is the capability to withstand the thermal gradient across the structures and the DIII-D vacuum vessel during operations and bakeout in which temperatures reach as high as 350 C. The performance of the diagnostics and divertor systems with experimental results of the two existing systems are reported in this paper along with the baseline of the designs of the three divertor systems

  7. Increased susceptibility of dystrophin-deficient brain to mild hypoxia

    International Nuclear Information System (INIS)

    Wallis, T.; Rae, C.; Bubb, W.A.; Head, S.I.

    2002-01-01

    Full text: Duchenne muscular dystrophy is an X-linked disorder resulting from total absence of the 427 kDa protein dystrophin. Dystrophin is normally expressed in the brain mainly in a neuronal subpopulation: cortical pyramidal cells, hippocampal CA1 neurons and cerebellar Purkinje cells. One suggested role for dystrophin is in colocalising mitochondrial creatine kinase with ADP translocase and ATP synthase in mitochondria. Brain tissue slices in the murine model of Duchenne dystrophy, the mdx mouse, have been shown to be more sensitive to hypoxia than control. In this work, we used 13 C NMR to monitor the metabolic response of mdx cortical brain tissue slices to normoxia (95%O 2 /5% CO 2 ) and mild hypoxia (95%air/5% CO 2 ). Under normoxic conditions, mdx cortical slices displayed increased net flux through the Krebs cycle and glutamate/glutamine cycle, consistent with the proposed GABA A lesion which results in decreased inhibitory input. By contrast, mild hypoxia resulted in a significant increase in the total pool size of lactate and decreased net flux of 13 C from [3- 13 C]pyruvate into glutamate C4, GABA C2 and Ala C2, as well as decreased anaplerotic activity as measured by the ratio of Asp C2: Asp C3 label. Mild hypoxia has a significantly greater effect on brain oxidative metabolism in mdx mice, than in control

  8. Electrical signaling, stomatal conductance, ABA and Ethylene content in avocado trees in response to root hypoxia

    Science.gov (United States)

    Gurovich, Luis; Schaffer, Bruce; García, Nicolás; Iturriaga, Rodrigo

    2009-01-01

    Avocado (Persea americana Mill.) trees are among the most sensitive of fruit tree species to root hypoxia as a result of flooded or poorly drained soil. Similar to drought stress, an early physiological response to root hypoxia in avocado is a reduction of stomatal conductance. It has been previously determined in avocado trees that an extracellular electrical signal between the base of stem and leaves is produced and related to reductions in stomatal conductance in response to drought stress. The current study was designed to determine if changes in the extracellular electrical potential between the base of the stem and leaves in avocado trees could also be detected in response to short-term (min) or long-term (days) root hypoxia, and if these signals could be related to stomatal conductance (gs), root and leaf ABA and ACC concentrations, ethylene emission from leaves and leaf abscission. In contrast to previous observations for drought-stressed trees, short-term or long-term root hypoxia did not stimulate an electrical potential difference between the base of the stem and leaves. Short-term hypoxia did not result in a significant decrease in gs compared with plants in the control treatment, and no differences in ABA concentration were found between plants subjected to hypoxia and control plants. Long-term hypoxia in the root zone resulted in a significant decrease in gs, increased leaf ethylene and increased leaf abscission. The results indicate that for avocado trees exposed to root hypoxia, electrical signals do not appear to be the primary root-to-shoot communication mechanism involved in signaling for stomatal closure as a result of hypoxia in the root zone. PMID:19649181

  9. Federating clinical data from six pediatric hospitals: process and initial results for microbiology from the PHIS+ consortium.

    Science.gov (United States)

    Gouripeddi, Ramkiran; Warner, Phillip B; Mo, Peter; Levin, James E; Srivastava, Rajendu; Shah, Samir S; de Regt, David; Kirkendall, Eric; Bickel, Jonathan; Korgenski, E Kent; Precourt, Michelle; Stepanek, Richard L; Mitchell, Joyce A; Narus, Scott P; Keren, Ron

    2012-01-01

    Microbiology study results are necessary for conducting many comparative effectiveness research studies. Unlike core laboratory test results, microbiology results have a complex structure. Federating and integrating microbiology data from six disparate electronic medical record systems is challenging and requires a team of varied skills. The PHIS+ consortium which is partnership between members of the Pediatric Research in Inpatient Settings (PRIS) network, the Children's Hospital Association and the University of Utah, have used "FURTHeR' for federating laboratory data. We present our process and initial results for federating microbiology data from six pediatric hospitals.

  10. The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer

    International Nuclear Information System (INIS)

    Starmans, Maud H.W.; Chu, Kenneth C.; Haider, Syed; Nguyen, Francis; Seigneuric, Renaud; Magagnin, Michael G.; Koritzinsky, Marianne; Kasprzyk, Arek; Boutros, Paul C.; Wouters, Bradly G.

    2012-01-01

    Background and purpose: Recent data suggest that in vitro and in vivo derived hypoxia gene-expression signatures have prognostic power in breast and possibly other cancers. However, both tumour hypoxia and the biological adaptation to this stress are highly dynamic. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and assist in predicting the impact of hypoxia on patient prognosis. Materials and methods: Transcriptome profiling was performed for three cell lines derived from diverse tumour-types after hypoxic exposure at eight time-points, which include a normoxic time-point. Time-dependent sets of co-regulated genes were identified from these data. Subsequently, gene ontology (GO) and pathway analyses were performed. The prognostic power of these novel signatures was assessed in parallel with previous in vitro and in vivo derived hypoxia signatures in a large breast cancer microarray meta-dataset (n = 2312). Results: We identified seven recurrent temporal and two general hypoxia signatures. GO and pathway analyses revealed regulation of both common and unique underlying biological processes within these signatures. None of the new or previously published in vitro signatures consisting of hypoxia-induced genes were prognostic in the large breast cancer dataset. In contrast, signatures of repressed genes, as well as the in vivo derived signatures of hypoxia-induced genes showed clear prognostic power. Conclusions: Only a subset of hypoxia-induced genes in vitro demonstrates prognostic value when evaluated in a large clinical dataset. Despite clear evidence of temporal patterns of gene-expression in vitro, the subset of prognostic hypoxia regulated genes cannot be identified based on temporal pattern alone. In vivo derived signatures appear to identify the prognostic hypoxia induced genes. The prognostic value of hypoxia-repressed genes is likely a surrogate for the known importance of

  11. [Damage effects of chronic hypoxia on medulla oblongata associated with oxidative stress and cell apoptosis].

    Science.gov (United States)

    Hou, Xuefei; Ding, Yan; Nie, Zheng; Li, Hui; Tang, Yuhong; Zhou, Hua; Chen, Li; Zheng, Yu

    2012-08-01

    The aim of this study is to study the damage effects of chronic hypoxia on medulla oblongata and to explore whether the damage is associated with oxidative stress and cell apoptosis. Adult male SD rats were randomly divided into two groups: control group and chronic hypoxia group. Medulla oblongata was obtained for the following methods of analyses. Nissl's staining was used to examine the Niss bodies of neurons in medullary respiratory related nuclei, biochemistry methods were utilized to examine oxidant stress damage induced by chronic hypoxia on medulla oblongata through measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and RT-PCR technique was used to study the influence of apoptosis induced by chronic hypoxia on medulla oblongata through analyzing the levels of Bax mRNA and Bcl-2 mRNA. The results showed the optical densities of Nissl's staining in pre-BötC, NA, NTS, FN, and 12N were significantly decreased in chronic hypoxia group in comparison with that in control group (P 0.05). Bax mRNA expression had no obvious change and Bcl-2 mRNA expression significantly decreased in chronic hypoxia group in comparison with that in control group (P < 0.05). The results suggest that chronic hypoxia could bring about serious damage to medullary respiratory centers through aggravating oxidative stress and increasing cell apoptosis.

  12. Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

    International Nuclear Information System (INIS)

    Yu, Lunyin; Hales, Charles A

    2011-01-01

    inhibition of tumor progression. The results from this study provide new insights into the role of hypoxia in tumor progression and therapeutic strategies for cancer treatment

  13. Hypoxia attenuates inflammatory mediators production induced by Acanthamoeba via Toll-like receptor 4 signaling in human corneal epithelial cells

    International Nuclear Information System (INIS)

    Pan, Hong; Wu, Xinyi

    2012-01-01

    , our results demonstrated that hypoxia attenuated the host immune and inflammatory response against Acanthamoeba infection by suppressing TLR4 signaling, indicating that hypoxia might impair the host cell’s ability to eliminate the Acanthamoeba invasion and that hypoxia could enhance cell susceptibility to Acanthamoeba infection. These results may explain why contact lens use is one of the most prominent risk factors for AK.

  14. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    International Nuclear Information System (INIS)

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-01-01

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  15. Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia

    Science.gov (United States)

    Limberg, Jacqueline K.; Johnson, Blair D.; Holbein, Walter W.; Ranadive, Sushant M.; Mozer, Michael T.

    2015-01-01

    Human studies use varying levels of low-dose (1-4 μg·kg−1·min−1) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1–4 μg·kg−1·min−1) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg−1·min−1. Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P HVR in the high group only (P HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg−1·min−1) and total peripheral resistance (1–4 μg·kg−1·min−1), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage. PMID:26586909

  16. Interindividual variability in the dose-specific effect of dopamine on carotid chemoreceptor sensitivity to hypoxia.

    Science.gov (United States)

    Limberg, Jacqueline K; Johnson, Blair D; Holbein, Walter W; Ranadive, Sushant M; Mozer, Michael T; Joyner, Michael J

    2016-01-15

    Human studies use varying levels of low-dose (1-4 μg·kg(-1)·min(-1)) dopamine to examine peripheral chemosensitivity, based on its known ability to blunt carotid body responsiveness to hypoxia. However, the effect of dopamine on the ventilatory responses to hypoxia is highly variable between individuals. Thus we sought to determine 1) the dose response relationship between dopamine and peripheral chemosensitivity as assessed by the ventilatory response to hypoxia in a cohort of healthy adults, and 2) potential confounding cardiovascular responses at variable low doses of dopamine. Young, healthy adults (n = 30, age = 32 ± 1, 24 male/6 female) were given intravenous (iv) saline and a range of iv dopamine doses (1-4 μg·kg(-1)·min(-1)) prior to and throughout five hypoxic ventilatory response (HVR) tests. Subjects initially received iv saline, and after each HVR the dopamine infusion rate was increased by 1 μg·kg(-1)·min(-1). Tidal volume, respiratory rate, heart rate, blood pressure, and oxygen saturation were continuously measured. Dopamine significantly reduced HVR at all doses (P HVR in the high group only (P HVR in the low group (P > 0.05). Dopamine infusion also resulted in a reduction in blood pressure (3 μg·kg(-1)·min(-1)) and total peripheral resistance (1-4 μg·kg(-1)·min(-1)), driven primarily by subjects with low baseline chemosensitivity. In conclusion, we did not find a single dose of dopamine that elicited a nadir HVR in all subjects. Additionally, potential confounding cardiovascular responses occur with dopamine infusion, which may limit its usage. Copyright © 2016 the American Physiological Society.

  17. Effect of acadesine on breast cancer cells under hypoxia

    Directory of Open Access Journals (Sweden)

    A. M. Shcherbakov

    2017-01-01

    Full Text Available The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК, an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen, acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia, acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

  18. Progressive hypoxia decouples activity and aerobic performance of skate embryos.

    Science.gov (United States)

    Di Santo, Valentina; Tran, Anna H; Svendsen, Jon C

    2016-01-01

    Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, S crit). Below S crit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation.

  19. The yeast genome may harbor hypoxia response elements (HRE).

    Science.gov (United States)

    Ferreira, Túlio César; Hertzberg, Libi; Gassmann, Max; Campos, Elida Geralda

    2007-01-01

    The hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor activated when cells are submitted to hypoxia. The heterodimer is composed of two subunits, HIF-1alpha and the constitutively expressed HIF-1beta. During normoxia, HIF-1alpha is degraded by the 26S proteasome, but hypoxia causes HIF-1alpha to be stabilized, enter the nucleus and bind to HIF-1beta, thus forming the active complex. The complex then binds to the regulatory sequences of various genes involved in physiological and pathological processes. The specific regulatory sequence recognized by HIF-1 is the hypoxia response element (HRE) that has the consensus sequence 5'BRCGTGVBBB3'. Although the basic transcriptional regulation machinery is conserved between yeast and mammals, Saccharomyces cerevisiae does not express HIF-1 subunits. However, we hypothesized that baker's yeast has a protein analogous to HIF-1 which participates in the response to changes in oxygen levels by binding to HRE sequences. In this study we screened the yeast genome for HREs using probabilistic motif search tools. We described 24 yeast genes containing motifs with high probability of being HREs (p-value<0.1) and classified them according to biological function. Our results show that S. cerevisiae may harbor HREs and indicate that a transcription factor analogous to HIF-1 may exist in this organism.

  20. Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

    Science.gov (United States)

    Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

    2017-06-01

    Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

  1. HIF1 Contributes to Hypoxia-Induced Pancreatic Cancer Cells Invasion via Promoting QSOX1 Expression

    Directory of Open Access Journals (Sweden)

    Chen-Ye Shi

    2013-08-01

    Full Text Available Background: Quiescin sulfhydryl oxidase 1 (QSOX1, which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. Methods: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1. Small interfering RNA (siRNA was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. Results: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. Conclusion: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

  2. Nocturnal hypoxia in ALS is related to cognitive dysfunction and can occur as clusters of desaturations.

    Directory of Open Access Journals (Sweden)

    Su-Yeon Park

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS.Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night and their clinical characteristics and cognitive function were compared.Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40% had poor memory retention (p = 0.039 and retrieval efficiency (p = 0.045. A cluster-of-desaturation pattern was identified in 7 patients (70% in the Hypoxia Group.These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation-reoxygenation (a cluster-of-desaturation pattern during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.

  3. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

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    Bethany L Peterson

    Full Text Available Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6 and older (postnatal day 20 age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  4. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

    Science.gov (United States)

    Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

    2012-01-01

    Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  5. Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia

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    Stephen A Brose

    2016-11-01

    Full Text Available Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA biosynthesis (FAS followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FAS maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FAS inhibition on NADH2+/NAD+ and NADPH2+/NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FAS inhibitors, TOFA (inhibits Acetyl-CoA carboxylase and cerulenin (inhibits FA synthase, increased NADH2+/NAD+ and NADPH2+/NADP+ ratios under hypoxia. Further, FAS inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

  6. Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.

    Science.gov (United States)

    Brose, Stephen A; Golovko, Svetlana A; Golovko, Mikhail Y

    2016-01-01

    Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased [Formula: see text]/NAD + and [Formula: see text]/NADP + ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.

  7. Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

    Science.gov (United States)

    Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

    2017-08-01

    Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  8. Hypoxia: From Placental Development to Fetal Programming.

    Science.gov (United States)

    Fajersztajn, Lais; Veras, Mariana Matera

    2017-10-16

    Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Hypoxia-inducible factor-1α upregulation in microglia following hypoxia protects against ischemia-induced cerebral infarction.

    Science.gov (United States)

    Huang, Tao; Huang, Weiyi; Zhang, Zhiqiang; Yu, Lei; Xie, Caijun; Zhu, Dongan; Peng, Zizhuang; Chen, Jiehan

    2014-10-01

    Activated microglia were considered to be the toxic inflammatory mediators that induce neuron degeneration after brain ischemia. Hypoxia can enhance the expression of hypoxia-inducible factor-1α (HIF-1α) in microglia and cause microglial activation. However, intermittent hypoxia has been reported recently to be capable of protecting the body from myocardial ischemia. We established a high-altitude environment as the hypoxic condition in this study. The hypoxic condition displayed a neuroprotective effect after brain ischemia, and mice exposed to this condition presented better neurological performance and smaller infarct size. At the same time, a high level of HIF-1α, low level of isoform of nitric oxide synthase, and a reduction in microglial activation were also seen in ischemic focus of hypoxic mice. However, this neuroprotective effect could be blocked by 2-methoxyestradiol, the HIF-1α inhibitor. Our finding suggested that HIF-1α expression was involved in microglial activation in vitro and was regulated by oxygen supply. The microglia were inactivated by re-exposure to hypoxia, which might be due to overexpression of HIF-1α. These results indicated that hypoxic conditions can be exploited to achieve maximum neuroprotection after brain ischemia. This mechanism possibly lies in microglial inactivation through regulation of the expression of HIF-1α.

  10. Dynamics and distribution of natural and human-caused hypoxia

    Science.gov (United States)

    Rabalais, N. N.; Díaz, R. J.; Levin, L. A.; Turner, R. E.; Gilbert, D.; Zhang, J.

    2010-02-01

    Water masses can become undersaturated with oxygen when natural processes alone or in combination with anthropogenic processes produce enough organic carbon that is aerobically decomposed faster than the rate of oxygen re-aeration. The dominant natural processes usually involved are photosynthetic carbon production and microbial respiration. The re-supply rate is indirectly related to its isolation from the surface layer. Hypoxic water masses (hypoxic areas has been exacerbated by any combination of interactions that increase primary production and accumulation of organic carbon leading to increased respiratory demand for oxygen below a seasonal or permanent pycnocline. Nutrient loading is likely to increase further as population growth and resource intensification rises, especially with increased dependency on crops using fertilizers, burning of fossil fuels, urbanization, and waste water generation. It is likely that the occurrence and persistence of hypoxia will be even more widespread and have more impacts than presently observed. Global climate change will further complicate the causative factors in both natural and human-caused hypoxia. The likelihood of strengthened stratification alone, from increased surface water temperature as the global climate warms, is sufficient to worsen hypoxia where it currently exists and facilitate its formation in additional waters. Increased precipitation that increases freshwater discharge and flux of nutrients will result in increased primary production in the receiving waters up to a point. The interplay of increased nutrients and stratification where they occur will aggravate and accelerate hypoxia. Changes in wind fields may expand oxygen minimum zones onto more continental shelf areas. On the other hand, not all regions will experience increased precipitation, some oceanic water temperatures may decrease as currents shift, and frequency and severity of tropical storms may increase and temporarily disrupt hypoxia more

  11. Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT

    Science.gov (United States)

    Leszczynska, Katarzyna B.; Foskolou, Iosifina P.; Abraham, Aswin G.; Anbalagan, Selvakumar; Tellier, Céline; Haider, Syed; Span, Paul N.; O’Neill, Eric E.; Buffa, Francesca M.; Hammond, Ester M.

    2015-01-01

    Restoration of hypoxia-induced apoptosis in tumors harboring p53 mutations has been proposed as a potential therapeutic strategy; however, the transcriptional targets that mediate hypoxia-induced p53-dependent apoptosis remain elusive. Here, we demonstrated that hypoxia-induced p53-dependent apoptosis is reliant on the DNA-binding and transactivation domains of p53 but not on the acetylation sites K120 and K164, which, in contrast, are essential for DNA damage–induced, p53-dependent apoptosis. Evaluation of hypoxia-induced transcripts in multiple cell lines identified a group of genes that are hypoxia-inducible proapoptotic targets of p53, including inositol polyphosphate-5-phosphatase (INPP5D), pleckstrin domain–containing A3 (PHLDA3), sulfatase 2 (SULF2), B cell translocation gene 2 (BTG2), cytoplasmic FMR1-interacting protein 2 (CYFIP2), and KN motif and ankyrin repeat domains 3 (KANK3). These targets were also regulated by p53 in human cancers, including breast, brain, colorectal, kidney, bladder, and melanoma cancers. Downregulation of these hypoxia-inducible targets associated with poor prognosis, suggesting that hypoxia-induced apoptosis contributes to p53-mediated tumor suppression and treatment response. Induction of p53 targets, PHLDA3, and a specific INPP5D transcript mediated apoptosis in response to hypoxia through AKT inhibition. Moreover, pharmacological inhibition of AKT led to apoptosis in the hypoxic regions of p53-deficient tumors and consequently increased radiosensitivity. Together, these results identify mediators of hypoxia-induced p53-dependent apoptosis and suggest AKT inhibition may improve radiotherapy response in p53-deficient tumors. PMID:25961455

  12. Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults.

    Science.gov (United States)

    Newhouse, Lauren P; Joyner, Michael J; Curry, Timothy B; Laurenti, Marcello C; Man, Chiara Dalla; Cobelli, Claudio; Vella, Adrian; Limberg, Jacqueline K

    2017-01-01

    An independent association exists between sleep apnea and diabetes. Animal models suggest exposure to intermittent hypoxia, a consequence of sleep apnea, results in altered glucose metabolism and fasting hyperglycemia. However, it is unknown if acute exposure to intermittent hypoxia increases glucose concentrations in nondiabetic humans. We hypothesized plasma glucose would be increased from baseline following 3 h of intermittent hypoxia in healthy humans independent of any effect on insulin sensitivity. Eight (7M/1F, 21-34 years) healthy subjects completed two study visits randomized to 3 h of intermittent hypoxia or continuous normoxia, followed by an oral glucose tolerance test. Intermittent hypoxia consisted of 25 hypoxic events per hour where oxygen saturation (SpO 2 ) was significantly reduced (Normoxia: 97 ± 1%, Hypoxia: 90 ± 2%, P  0.05). In contrast, circulating glucose concentrations were increased after 3 h of intermittent hypoxia when compared to baseline (5.0 ± 0.2 vs. 5.3 ± 0.2 mmol/L, P = 0.01). There were no detectable changes in insulin sensitivity following intermittent hypoxia when compared to continuous normoxia, as assessed by the oral glucose tolerance test (P > 0.05). Circulating glucose is increased after 3 h of intermittent hypoxia in healthy humans, independent of any lasting changes in insulin sensitivity. These novel findings could explain, in part, the high prevalence of diabetes in patients with sleep apnea and warrant future studies to identify underlying mechanisms. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Stromal Expression of Hypoxia Regulated Proteins Is an Adverse Prognostic Factor in Colorectal Carcinomas

    Directory of Open Access Journals (Sweden)

    Arjen H. G. Cleven

    2007-01-01

    Full Text Available Background: Hypoxia modifies the phenotype of tumors in a way that promotes tumor aggressiveness and resistance towards chemotherapy and radiotherapy. However, the expression and influence of hypoxia-regulated proteins on tumor biology are not well c