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Sample records for hemoglobinuria receiving eculizumab

  1. Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review.

    PubMed

    Miyasaka, Naoyuki; Miura, Osamu; Kawaguchi, Tatsuya; Arima, Nobuyoshi; Morishita, Eriko; Usuki, Kensuke; Morita, Yasuyoshi; Nishiwaki, Kaichi; Ninomiya, Haruhiko; Gotoh, Akihiko; Imashuku, Shinsaku; Urabe, Akio; Shichishima, Tsutomu; Nishimura, Jun-Ichi; Kanakura, Yuzuru

    2016-06-01

    Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) is associated with significant risk of complications, such as life-threatening thrombosis. Recently, eculizumab has come into clinical use and revolutionized the treatment of PNH. However, clinical information regarding eculizumab use for PNH during pregnancy is limited. The present report describes pregnancies with PNH treated with eculizumab that were registered with the Japan PNH study group and reviews the literature. In case 1, the patient received eculizumab throughout pregnancy and delivered a healthy neonate at term, although breakthrough hemolysis occurred at 20 weeks of gestation. In case 2, the patient discontinued eculizumab before pregnancy and developed preeclampsia at 27 weeks of gestation. She received eculizumab and delivered a preterm, but healthy, neonate by cesarean section. In case 3, the patient received eculizumab from 18 weeks of gestation and delivered a healthy neonate at term without any complications. Reports of 11 pregnant women treated with eculizumab were identified in the literature. Of 14 pregnancies, including our own cases, breakthrough hemolysis and preeclampsia occurred in five and two cases, respectively. There were no thrombotic complications, maternal or neonatal deaths, or fetal structural abnormalities. Thus, eculizumab appears to be safe and effective for managing PNH during pregnancy. PMID:26857155

  2. Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no-treatment study.

    PubMed

    Loschi, Michael; Porcher, Raphael; Barraco, Fiorenza; Terriou, Louis; Mohty, Mohamad; de Guibert, Sophie; Mahe, Beatrice; Lemal, Richard; Dumas, Pierre-Yves; Etienne, Gabriel; Jardin, Fabrice; Royer, Bruno; Bordessoule, Dominique; Rohrlich, Pierre Simon; Fornecker, Luc Mathieu; Salanoubat, Celia; Maury, Sebastien; Cahn, Jean-Yves; Vincent, Laure; Sene, Thomas; Rigaudeau, Sophie; Nguyen, Stephanie; Lepretre, Anne-Claire; Mary, Jean-Yves; Corront, Bernadette; Socie, Gerard; Peffault de Latour, Regis

    2016-06-01

    Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P = 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20-34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution. Am. J. Hematol. 91:366-370, 2016. © 2016 Wiley Periodicals, Inc. PMID:26689746

  3. Eculizumab effect on the hemostatic state in patients with paroxysmal nocturnal hemoglobinuria.

    PubMed

    Seregina, E A; Tsvetaeva, N V; Nikulina, O F; Zapariy, A P; Erasov, A V; Gribkova, I V; Orel, E B; Ataullakhanov, F I; Balandina, A N

    2015-02-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by a hypercoagulable state associated with acute hemolysis. Eculizumab is used to reduce the intensity of intravascular hemolysis in PNH patients. The hemostatic status of three patients with PNH was assessed during eculizumab treatment by D-dimer assay and the global assays: thromboelastography (TEG), thrombin generation test (TGТ), and thrombodynamics (TD). In the state of hemolytic crisis before the therapy D-dimer concentration was increased in two patients accompanied by hypercoagulation changes in TEG parameter angle (α). TD parameter the clot growth velocity (V) revealed hypercoagulability while TGT parameter ETP was within the normal range in all patients. The lactate dehydrogenase (LDH) activity decreased during the 8months of eculizumab therapy. The physical health was improved, the frequency of hemolytic crisis decreased. Patients periodically exhibited hypercoagulable state: the mean values α=38±11° (with normal range 20-40°), ETP=1311±442nM·min (with normal range 800-1560nM·min), V=31±4μm/min (with normal range 20-29μm/min). During the eculizumab therapy two patients had the repeated clinical manifestation of acute hemolytic crisis, the parameters of the global tests were increased compared to the previous measurement. The global hemostasis tests TEG, TGT and TD revealed hypercoagulability in patients with PNH during eculizumab therapy. PMID:25497169

  4. Long Standing Eculizumab Treatment without Anticoagulant Therapy in High-Risk Thrombogenic Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Al-Jafar, Hassan A.; AlDallal, Salma M.; Askar, Haifa A.; Aljeraiwi, Ali M.; Al-Alansari, Ahmad

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan disease affecting all hematopoietic cell types. The abnormality of red blood cells in this disease predisposes to intravascular complement-mediated hemolysis. Eculizumab is an orphan drug used to treat this rare disease. Thrombosis is the key cause of death in PNH patients in about 40% to 67% of cases. We report the case of a woman presenting with PNH complicated with serious Budd-Chiari syndrome thrombosis and with a stent inserted in the portal vein. She refused to take any anticoagulant treatment since she commenced eculizumab 4 years before. No thrombotic events happened since that time. This case could add an extra benefit for eculizumab, which could be used as an anti-thromboembolic prophylactic agent in PNH, especially in patients with thrombocytopenia, where the use of anticoagulant agents is extremely hazardous. More randomized studies might establish the use of eculizumab without anticoagulants to avoid serious bleeding that could happen in thrombocytopenic PNH patients. PMID:26487933

  5. Eculizumab in the management of paroxysmal nocturnal hemoglobinuria: patient selection and special considerations

    PubMed Central

    Al-Ani, Fatimah; Chin-Yee, Ian; Lazo-Langner, Alejandro

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder resulting from somatic mutation in the PIG-A gene leading to a deficiency of the membrane-anchoring molecule glycosylphosphatidylinositol. The lack of expression of two glycosylphosphatidylinositol-anchored proteins involved in the regulation of the complement system renders PNH erythrocytes susceptible to complement-mediated lysis. Clinical manifestations include thromboembolic disease, chronic kidney injury, pulmonary hypertension, smooth muscle dysfunction, and chronic hemolysis. Until recently, treatment was mainly supportive with most patients suffering from significant morbidity and shortened survival compared to age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has resulted in dramatic improvements of survival and reduction in complications. In this paper, we review some special considerations pertaining to the use of eculizumab for PNH. PMID:27536121

  6. Eculizumab in the management of paroxysmal nocturnal hemoglobinuria: patient selection and special considerations.

    PubMed

    Al-Ani, Fatimah; Chin-Yee, Ian; Lazo-Langner, Alejandro

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder resulting from somatic mutation in the PIG-A gene leading to a deficiency of the membrane-anchoring molecule glycosylphosphatidylinositol. The lack of expression of two glycosylphosphatidylinositol-anchored proteins involved in the regulation of the complement system renders PNH erythrocytes susceptible to complement-mediated lysis. Clinical manifestations include thromboembolic disease, chronic kidney injury, pulmonary hypertension, smooth muscle dysfunction, and chronic hemolysis. Until recently, treatment was mainly supportive with most patients suffering from significant morbidity and shortened survival compared to age-matched controls. The development of eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has resulted in dramatic improvements of survival and reduction in complications. In this paper, we review some special considerations pertaining to the use of eculizumab for PNH. PMID:27536121

  7. Hemoglobinuria test

    MedlinePlus

    ... Hemolytic uremic syndrome (HUS) Kidney infection Kidney tumor Malaria Paroxysmal nocturnal hemoglobinuria Paroxysmal cold hemoglobinuria Sickle cell ... nephritic syndrome Burns Hemolytic anemia Hemolytic-uremic syndrome Malaria Paroxysmal nocturnal hemoglobinuria (PNH) Pulmonary tuberculosis Renal cell ...

  8. Hemoglobinuria after fraternity hazing.

    PubMed

    Baker, B A; Schwartz, K A; Segan, D J; Mayor, G H

    1982-09-01

    We describe a 19-year-old male who presented with traumatic hemoglobinuria. We hypothesize that this patient has a genetic haptoglobin variant with a low hemoglobin binding capacity which resulted in hemoglobinuria after physical fraternity hazing. A review of the literature regarding traumatic hemoglobinuria supports the association between decreased baseline plasma haptoglobin levels and hemoglobinuria after trauma. PMID:7124724

  9. Therapeutic drug monitoring of eculizumab: Rationale for an individualized dosing schedule

    PubMed Central

    Gatault, Philippe; Brachet, Guillaume; Ternant, David; Degenne, Danielle; Récipon, Guillaume; Barbet, Christelle; Gyan, Emmanuel; Gouilleux-Gruart, Valérie; Bordes, Cécile; Farrell, Alexandra; Halimi, Jean Michel; Watier, Hervé

    2015-01-01

    The annual cost of eculizumab maintenance therapy in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic–uremic syndrome (aHUS) exceeds $300,000 per patient. A better understanding of eculizumab pharmacokinetics and subsequent individual dose adjustment could reduce this cost. We measured the trough eculizumab concentration in 9 patients with maintenance therapy (aHUS, n = 7; PNH, n = 2) and determined: 1) the intra- and inter-individual variability; 2) the influence of weight on eculizumab pharmacokinetics; and 3) the rate of elimination of eculizumab following discontinuation. A one-compartment model was developed to describe the pharmacokinetics of eculizumab and predicted complement activity by body weight. Trough eculizumab concentrations were >50 µg/mL in 9/9, >100 µg/mL in 8/9, and >300 µg/mL in 5/9 of patients. Intra-individual variability was low but eculizumab concentrations, closely correlated with patient weight (R2 = 0.66, p = 0.034), varied broadly (55 ± 12 to 733 ± 164 µg/mL). Pharmacokinetic modeling showed that the elimination half-life varied greatly, with an increase from 7.8 d in a patient weighing 100 kg to 19.5 d in a 40 kg patient. We predicted that infusions of 1200 mg could be spaced every 4 or 6 weeks in patients weighing <90 and <70 kg, respectively. In this pilot study, the current recommended use of a fixed eculizumab dose for maintenance therapy is associated with excessively high trough concentrations in many patients. Further prospective larger studies are now required to support an individualized schedule adjusted for patient weight and based on the observed trough serum eculizumab concentration. PMID:26337866

  10. Presentation and Management of Paroxysmal Nocturnal Hemoglobinuria: A Single-Center Experience

    PubMed Central

    Karakuş, Abdullah; Ekmen, Mehmet Önder; Ayyildiz, Orhan

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis. Real-world experience of PNH management is largely unreported. A retrospective analysis was undertaken based on medical records from six patients with PNH [two with aplastic anemia (AA)] treated at our center, Dicle University, Turkey. Diagnosis was based on granulocyte PNH clones, ranging from 93% to 66%. All patients had symptoms consistent with PNH. One patient was managed adequately with supportive measures only. Five were treated with the complement inhibitor eculizumab. Follow-up data (<1 year) were available in four cases (the fifth had received only three infusions by final follow-up). Hemoglobin level in these four patients increased from 4.1-7.2 g/dL to 8.3-13.0 g/dL. Lactate dehydrogenase, a marker for hemolysis, decreased profoundly in the two non-AA patients, with more minor improvements in the two AA patients. Weakness and fatigue improved in all eculizumab-treated patients. Four of the five treated patients became transfusion independent, including the patient given only three infusions. In the remaining case, a patient with AA, transfusion requirement decreased, and abdominal pain and dysphagia resolved. No adverse events occurred. PNH can be successfully managed in routine practice. PMID:27103981

  11. Stratification of responders towards eculizumab using a structural epitope mapping strategy

    PubMed Central

    Volk, Anna-Luisa; Hu, Francis Jingxin; Berglund, Magnus M.; Nordling, Erik; Strömberg, Patrik; Uhlen, Mathias; Rockberg, Johan

    2016-01-01

    The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics. PMID:27509843

  12. Stratification of responders towards eculizumab using a structural epitope mapping strategy.

    PubMed

    Volk, Anna-Luisa; Hu, Francis Jingxin; Berglund, Magnus M; Nordling, Erik; Strömberg, Patrik; Uhlen, Mathias; Rockberg, Johan

    2016-01-01

    The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics. PMID:27509843

  13. Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria

    PubMed Central

    Sahin, Fahri; Ozkan, Melda Comert; Mete, Nihal Gokmen; Yilmaz, Mumtaz; Oruc, Nevin; Gurgun, Alev; Kayikcioglu, Meral; Guler, Ayse; Gokcay, Figen; Bilgir, Ferda; Ceylan, Cengiz; Bilgir, Oktay; Sari, Ismail Hakan; Saydam, Guray

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease caused by clonal expansion of one or more hematopoietic stem cell (HSC) lines due to a somatic mutation of the phosphatidylinositol glycan anchor (PIG-A) gene located on Xp22.1. PNH incidence is 1.5-2 cases per million of the population per year. PNH can affect multiple systems in the body and requires multidisciplinary clinical management. Patients can manifest with severe pancytopenia, life-threatening thrombosis affecting the hepatic, abdominal, cerebral, and subdermal veins, and high requirements for blood transfusion due to haemolytic anemia. PNH can also be associated with bone marrow failure. Advances in diagnostic techniques and a targeted therapeutic approach for PNH have emerged in the last two decades. Eculizumab, a promising humanized monoclonal antibody against C5, is the first approved therapy for PNH. PMID:26171279

  14. Eculizumab in Typical Hemolytic Uremic Syndrome (HUS) With Neurological Involvement

    PubMed Central

    Pape, Lars; Hartmann, Hans; Bange, Franz Christoph; Suerbaum, Sebastian; Bueltmann, Eva; Ahlenstiel-Grunow, Thurid

    2015-01-01

    Abstract In typical hemolytic uremic syndrome (HUS) approximately 25% of patients show central nervous system (CNS) involvement often leading to serious long-term disabilities. We used the C5-complement inhibitor Eculizumab as rescue therapy. From 2011 to 2014, 11 children (median age 22 months, range 11–175) with enterohemorrhagic Escherichia coli-positive HUS requiring dialysis who had seizures (11/11) and/or were in a stupor or coma (10/11) were treated with Eculizumab. Two patients enrolled on the Safety and Efficacy Study of Eculizumab in Shiga-Toxin Producing E coli Hemolytic-Uremic Syndrome (STEC-HUS) each received 6 doses of Eculizumab, 3 patients 2 doses, and 6 patients 1 dose. Laboratory diagnostics of blood samples and magnetic resonance imaging (MRI) were performed as per center practice. Data were analyzed retrospectively. Cranial MRI was abnormal in 8 of 10 patients with findings in the basal ganglia and/or white matter. A 2-year-old boy with severe cardiac involvement and status epilepticus needed repeated cardio-pulmonary resuscitation and extracorporeal membrane oxygenation. He died 8 days after start of Eculizumab treatment. Two patients with hemorrhagic colitis and repeated seizures required artificial ventilation for 6 and 16 days, respectively. At the time of discharge, 1 patient showed severe neurological impairment and 1 mild neurological impairment. The 8 surviving patients experienced no further seizures after the first dose of Eculizumab. Three patients showed mild neurological impairment at discharge, whilst the remaining 5 showed no impairment. The platelets normalized 4 days (median) after the first dose of Eculizumab (range 0–20 days). The mean duration of dialysis after the first dose of Eculizumab was 14.1 ± 6.1 days. In children with typical HUS and CNS involvement early use of Eculizumab appears to improve neurological outcome. In severe HUS cases which progress rapidly with multiple organ involvement, late treatment with

  15. Recent advances in the pathogenesis and treatment of paroxysmal nocturnal hemoglobinuria

    PubMed Central

    Luzzatto, Lucio

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare disease that has been investigated for over one century and has revealed unique aspects of the pathogenesis and pathophysiology of a hemolytic anemia. PNH results from expansion of a clone of hematopoietic cells that, as a consequence of an inactivating mutation of the X-linked gene PIG-A, are deficient in glycosylphosphatidylinositol (GPI)-linked proteins: since these include the surface membrane complement-regulatory proteins CD55 and CD59, the red cells arising from this clone are exquisitely sensitive to lysis by activated complement. Until a decade ago, the treatment options for PNH were either supportive treatment – often including blood transfusion, anti-thrombosis prophylaxis, and sometimes thrombolytic therapy – or allogeneic bone marrow transplantation. Since 2007, PNH has received renewed and much wider attention because a new form of treatment has become available, namely complement blockade through the anti-C5 monoclonal antibody eculizumab. This brief review focuses on two specific aspects of PNH: (1) response to eculizumab, variability of response, and how this new agent has impacted favorably on the outlook and on the quality of life of patients; and (2) with respect to pathogenesis, new evidence supports the notion that expansion of the PNH clone results from T-cell-mediated auto-immune damage to hematopoietic stem cells, with the GPI molecule as target. Indeed, GPI-specific CD8+ T cells – which have been identified in PNH patients – would spare selectively GPI-negative stem cells, thus enabling them to re-populate the marrow of a patient who would otherwise have aplastic anemia. PMID:26962442

  16. Recent advances in the pathogenesis and treatment of paroxysmal nocturnal hemoglobinuria.

    PubMed

    Luzzatto, Lucio

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare disease that has been investigated for over one century and has revealed unique aspects of the pathogenesis and pathophysiology of a hemolytic anemia. PNH results from expansion of a clone of hematopoietic cells that, as a consequence of an inactivating mutation of the X-linked gene PIG-A, are deficient in glycosylphosphatidylinositol (GPI)-linked proteins: since these include the surface membrane complement-regulatory proteins CD55 and CD59, the red cells arising from this clone are exquisitely sensitive to lysis by activated complement. Until a decade ago, the treatment options for PNH were either supportive treatment - often including blood transfusion, anti-thrombosis prophylaxis, and sometimes thrombolytic therapy - or allogeneic bone marrow transplantation. Since 2007, PNH has received renewed and much wider attention because a new form of treatment has become available, namely complement blockade through the anti-C5 monoclonal antibody eculizumab. This brief review focuses on two specific aspects of PNH: (1) response to eculizumab, variability of response, and how this new agent has impacted favorably on the outlook and on the quality of life of patients; and (2) with respect to pathogenesis, new evidence supports the notion that expansion of the PNH clone results from T-cell-mediated auto-immune damage to hematopoietic stem cells, with the GPI molecule as target. Indeed, GPI-specific CD8+ T cells - which have been identified in PNH patients - would spare selectively GPI-negative stem cells, thus enabling them to re-populate the marrow of a patient who would otherwise have aplastic anemia. PMID:26962442

  17. Paroxysmal cold hemoglobinuria.

    PubMed

    Shanbhag, Satish; Spivak, Jerry

    2015-06-01

    Paroxysmal cold hemoglobinuria is a rare cause of autoimmune hemolytic anemia predominantly seen as an acute form in young children after viral illnesses and in a chronic form in some hematological malignancies and tertiary syphilis. It is a complement mediated intravascular hemolytic anemia associated with a biphasic antibody against the P antigen on red cells. The antibody attaches to red cells at colder temperatures and causes red cell lysis when blood recirculates to warmer parts of the body. Treatment is mainly supportive and with red cell transfusion, but immunosuppressive therapy may be effective in severe cases. PMID:26043386

  18. Variable eculizumab clearance requires pharmacodynamic monitoring to optimize therapy for thrombotic microangiopathy after hematopoietic stem cell transplantation

    PubMed Central

    Jodele, Sonata; Fukuda, Tsuyoshi; Mizuno, Kana; Vinks, Alexander A.; Laskin, Benjamin L.; Goebel, Jens; Dixon, Bradley P.; Chima, Ranjit S; Hirsch, Russel; Teusink, Ashley; Lazear, Danielle; Lane, Adam; Myers, Kasiani C.; Dandoy, Christopher E.; Davies, Stella M.

    2015-01-01

    Thrombotic microangiopathy (TMA) after hematopoietic stem cell transplant (HSCT) associated with terminal complement activation, as measured by elevated plasma terminal complement (sC5b-9) concentrations, has a very high mortality. The complement inhibitor eculizumab may be a therapeutic option for HSCT-associated TMA. We examined the pharmacokinetics and pharmacodynamics (PK/PD) of eculizumab in children and young adult HSCT recipients with TMA and activated complement to determine drug dosing requirements for future efficacy trials. We analyzed prospectively collected laboratory samples and clinical data from 18 HSCT recipients with high-risk TMA presenting with complement activation who were treated with eculizumab. We measured eculizumab serum concentrations, total hemolytic complement activity (CH50), and plasma sC5b-9 concentrations. Population PK/PD analyses correlated eculizumab concentrations with complement blockade and clinical response and determined inter-individual differences in PK parameters. We also compared transplant survival in patients treated with eculizumab (n=18) to patients with the same high-risk TMA features who did not receive any targeted therapy during a separate prospective observational study (n=11). In the PK analysis, we found significant inter-patient variability in eculizumab clearance, ranging from 16 to 237 mL/hr/70kg in the induction phase. The degree of complement activation measured by sC5b-9 concentrations at the start of therapy, in addition to actual body weight, were significant determinants of eculizumab clearance and disease response. Sixty one percent of treated patients had complete resolution of TMA and were able to safely discontinue eculizumab without disease recurrence. Overall survival was significantly higher in treated subjects compared to untreated patients (56% versus 9%, p=0.003). Complement blocking therapy is associated with improved survival in HSCT patients with high-risk TMA who historically have

  19. Complement Blockade with a C1 Esterase Inhibitor in Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    DeZern, Amy E.; Uknis, Marc; Yuan, Xuan; Mukhina, Galina L; Varela, Juan; Saye, JoAnne; Pu, Jeffrey; Brodsky, Robert A.

    2014-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, hematopoietic stem cell disorder that manifests with a complement-mediated hemolytic anemia, bone marrow failure and a propensity for thrombosis. These patients experience both intra- and extravascular hemolysis in the context of underlying complement activation. Currently eculizumab effectively blocks the intravascular hemolysis PNH. There remains an unmet clinical need for a complement inhibitor with activity early in the complement cascade to block complement at the classical and alternative pathways. C1 esterase inhibitor (C1INH) is an endogenous human plasma protein that has broad inhibitory activity in the complement pathway through inhibition of the classical pathway by binding C1r and C1s and inhibits the mannose-binding lectin-associated serine proteases in the lectin pathway. In this study, we show that commercially available plasma derived C1INH prevents lysis induced by the alternative complement pathway, of PNH erythrocytes in human serum. Importantly, C1INH was able to block the accumulation of C3 degradation products on CD55 deficient erythrocytes from PNH patient on eculizumab therapy. This could suggest a role for inhibition of earlier phases of the complement cascade than that currently inhibited by eculizumab for incomplete or non-responders to that therapy. PMID:25034232

  20. Notes from the Field: Meningococcal Disease in an International Traveler on Eculizumab Therapy - United States, 2015.

    PubMed

    Applegate, Allen O; Fong, Vanessa C; Tardivel, Kara; Lippold, Susan A; Zarate, Sheilah

    2016-01-01

    On June 2, 2015, CDC was notified that a male airline passenger, aged 41 years, with a fever of 105.4°F, headache, nausea, photophobia, diarrhea, and vomiting, which began approximately 3 hours after departure, was arriving to San Francisco, California, on a flight from Frankfurt, Germany. His symptoms reportedly started with neck stiffness 1 day earlier. Upon arrival, the patient was immediately transported to a local hospital, where he was in septic shock, which was followed by multisystem organ failure. Cerebrospinal fluid, obtained approximately 12 hours after initiation of treatment, was Gram stain- and culture-negative. Blood cultures, which were drawn before antibiotic treatment, were positive for Neisseria meningitides of indeterminate serogroup. A review of the patient's medical records revealed a history of paroxysmal nocturnal hemoglobinuria and current biweekly eculizumab (Soliris) therapy. PMID:27414068

  1. Disease Recurrence After Early Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome With Complement C3 I1157T Mutation.

    PubMed

    Toyoda, Hidemi; Wada, Hideo; Miyata, Toshiyuki; Amano, Keishiro; Kihira, Kentaro; Iwamoto, Shotaro; Hirayama, Masahiro; Komada, Yoshihiro

    2016-04-01

    Eculizumab, terminal complement inhibitor, has become the frontline treatment for atypical hemolytic uremic syndrome (aHUS). However, the optimal treatment schedule has not yet been established. We describe here an aHUS patient with a mutation of C3 I1157T who achieved remission with eculizumab and suffered a recurrence after eculizumab discontinuation, a clinical situation that has not been previously described in patients with C3 mutation. A 9-year-old male experienced an onset of aHUS after viral gastroenteritis and was treated with hemodialysis. At 13 years of age he developed bacterial enterocolitis due to Campylobacter jejuni and experienced a recurrence of aHUS. Eculizumab was initiated on day 4 after disease onset resulting in recovering laboratory parameters. The patient received eculizumab for 5 months before its discontinuation. Second relapse induced by bacterial pharyngitis was confirmed 4 months after eculizumab discontinuation and prompt eculizumab reinitiation resulted in rapid remission. The patients carrying mutations in CFH or C3 have a high frequency of relapse and worse prognosis. More than 50% of aHUS relapses occurred during the first year after the onset. Therefore, long-term treatment with eculizumab is appropriate in patients with aHUS who have experienced a relapse or have mutations associated with poor prognosis. PMID:26840081

  2. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.

    PubMed

    Greenbaum, Larry A; Fila, Marc; Ardissino, Gianluigi; Al-Akash, Samhar I; Evans, Jonathan; Henning, Paul; Lieberman, Kenneth V; Maringhini, Silvio; Pape, Lars; Rees, Lesley; van de Kar, Nicole C A J; Vande Walle, Johan; Ogawa, Masayo; Bedrosian, Camille L; Licht, Christoph

    2016-03-01

    Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children. PMID:26880462

  3. Cerebral Venous Thrombosis in Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Meppiel, Elodie; Crassard, Isabelle; de Latour, Régis Peffault; de Guibert, Sophie; Terriou, Louis; Chabriat, Hugues; Socié, Gérard; Bousser, Marie-Germaine

    2015-01-01

    Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells characterized by hemolytic anemia, marrow failure, and a high incidence of life-threatening venous thrombosis. Cerebral venous system is the second most frequent location of thrombosis after hepatic veins. However, data about PNH-related cerebral venous thrombosis (CVT) are very scarce because of the rarity of both the disorders. We report a French study about PNH patients with CVT. Patients were recruited retrospectively, from the Société Française d’Hématologie (SFH) registry of 465 patients with PNH; the Lariboisière registry of 399 patients with CVT; and a direct contact with 26 French Hematology Units. We review cases reported since 1938 in the English and French language literature. We then compared patients of our series with cases from the literature, with non-PNH-related CVT cases from Lariboisière registry, and with PNH patients without CVT from SFH registry. Fifteen patients were included between 1990 and 2012. Most patients were women (12/15) and half of them presented associated hormonal venous thrombosis risk factors. Three patients had concomitant hepatic vein thrombosis. CVT was the first manifestation of PNH in 4 patients. No major difference in CVT characteristics was found compared with non-PNH-related CVT cases, except for a younger age at diagnosis in PNH patients (P < 0.001). All patients were treated with anticoagulation therapy. One death occurred in acute stage. All surviving patients were independent 1 year after. Median survival time was 9 years. Recurrent thrombosis rate was 50% at 6 years, occurring in patients that did not have bone marrow transplantation or eculizumab therapy. Cases of death were mainly related to hepatic vein thrombosis. Prognosis of CVT was good in our series. However, these patients have a poor long-term prognosis due to PNH disease by itself. PNH treatment should be proposed as soon as possible to

  4. Eculizumab and Recurrent C3 Glomerulonephritis

    PubMed Central

    Gurkan, Sevgi; Fyfe, Billie; Weiss, Lynne; Xiao, Xue; Zhang, Yuzhou; Smith, Richard J.

    2015-01-01

    Background and objectives Hyperactivity of the alternative complement pathway is the principle defect in the C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease. Design, setting, participants & measurements In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of Dense Deposit Disease (DDD) and allograft recurrence of C3 (C3GN) glomerulonephritis was treated with eculizumab every-other-week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/d at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 months and 12 months. Results Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, during therapy it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease. Conclusions Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of alternative pathway remained, showing that eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients. PMID:23689905

  5. Advances in the Diagnosis and Therapy of Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Brodsky, Robert A.

    2008-01-01

    Summary PNH is an uncommon acquired hemolytic anemia that often manifests with hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis. The disease results from the expansion of hematopoietic stem cells harboring a mutation in a gene, PIG-A, that is required for the biosynthesis of a lipid moiety, glycosylphosphatidylinositol (GPI), that attaches dozens of different proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI anchored proteins; this deficiency on erythrocytes leads to intravascular hemolysis since certain GPI anchored proteins normally function as complement regulators. Free hemoglobin released from intravascular hemolysis leads to circulating nitric oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis. Interestingly, rare PIG-A mutations can be found in virtually all healthy control subjects leading to speculation that PIG-A mutations in hematopoietic stem cells are common benign events. However, recent data reveals that most of these mutations in healthy controls are not derived from stem cells. The recently FDA approved complement inhibitor eculizumab has been shown to decrease hemolysis, decrease erythrocyte transfusion requirements, decrease the risk for thrombosis and improve quality of life for PNH patients. PMID:18063459

  6. Paroxysmal nocturnal hemoglobinuria: a single Spanish center's experience over the last 40 yr.

    PubMed

    Muñoz-Linares, Cristina; Ojeda, Emilio; Forés, Rafael; Pastrana, Miguel; Cabero, Martín; Morillo, Daniel; Bautista, Guiomar; Baños, Isolina; Monteserín, Carmen; Bravo, Pilar; Jaro, Esther; Cedena, Teresa; Steegmann, Juan Luis; Villegas, Ana; Cabrera, José Rafael

    2014-10-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease. To date, many reviews and series have been described. We report the experience of our center by presenting a review of 56 PNH patient cases with an average age at diagnosis of 38 yr and follow-ups beginning at approximately 40 yr; the median survival rate was 11 yr. The average clonal size upon diagnosis was 48%, presenting a variable evolution. Thrombotic episodes and cancer were five each, and the main causes of death among our patients were equal at 8.9%. Radiological study by magnetic resonance imaging is presented as a fundamental technique for estimating the deposit of iron levels in the liver and kidney, as well as in some decisive cases at the start of eculizumab therapy. Sixteen patients have been treated with eculizumab so far in our series, and being a safe drug, it provides improvement in the patients' quality of life, and the disappearance of clinical symptoms, and avoids the emergence of new thrombosis. PMID:24758317

  7. Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature

    PubMed Central

    Boucher, Anne; Collette, Suzon; Senécal, Lynne

    2016-01-01

    In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined. PMID:27478676

  8. Compatible Transfusion Therapy for Paroxysmal Cold Hemoglobinuria

    ERIC Educational Resources Information Center

    Rausen, Aaron R.; And Others

    1975-01-01

    Presented are case histories of two children, ages 2 and 4 years, with paroxysmal cold hemoglobinuria (PCH, a syndrome characterized by acute intravascular hemoglobin dissolution and hemoglobin in the urine). (Author/CL)

  9. Eculizumab Salvage Therapy for Antibody-Mediated Rejection in a Desensitization-Resistant Intestinal Re-Transplant Patient.

    PubMed

    Fan, J; Tryphonopoulos, P; Tekin, A; Nishida, S; Selvaggi, G; Amador, A; Jebrock, J; Weppler, D; Levi, D; Vianna, R; Ruiz, P; Tzakis, A

    2015-07-01

    The presence of elevated calculated panel reactive antibody (cPRA) and anti-HLA donor specific antibodies (DSA) are high risk factors for acute antibody-mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization-resistant intestinal re-transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut-off value of 3000 MFI and remains rejection free with a 2-year follow-up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization-resistant patients. PMID:25649227

  10. Can eculizumab be discontinued in aHUS?

    PubMed Central

    Sahutoglu, Tuncay; Basturk, Taner; Sakaci, Tamer; Koc, Yener; Ahbap, Elbis; Sevinc, Mustafa; Kara, Ekrem; Akgol, Cuneyt; Caglayan, Feyza Bayraktar; Unsal, Abdulkadir; Daha, Mohamed R.

    2016-01-01

    Abstract Background: The management of atypical hemolytic uremic syndrome (aHUS) has evolved into better control of thrombotic microangiopathy (TMA) and recovery of renal functions since the recent introduction of the terminal complement cascade blocker, eculizumab, into clinical use. Better characterization of genotype–phenotype relations has become possible with genetic and clinical studies. However, these advances brought up some important issues, such as the possibility and timing of discontinuation of eculizumab and strategy of follow-up that need to be enlightened. Case Summary: One of our aHUS cases with a novel complement factor H mutation, who developed unusual laboratory findings (thrombocytopenia and mild creatinine elevation without other features of TMA) following discontinuation of eculizumab was presented. Literature and case reports relevant to discontinuation of eculizumab in aHUS patients were reviewed. Conclusion: Limited experience suggests that the risk of recurrence of TMA following discontinuation of eculizumab is relatively low for patients with MCP mutations, homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no identifiable mutations, whereas there is a major risk for patients with CFH mutations. Early detection of TMA recurrence and prompt retreatment with eculizumab seem to be efficient in controlling of TMA and restoration of kidney functions. PMID:27495036

  11. [THE METHODICAL APPROACHES TO DIAGNOSTIC OF NIGHT PAROXYSMAL HEMOGLOBINURIA].

    PubMed

    Plekhanova, O S; Naumova, E V; Lugovskaya, S A; Potchtar, M E; Bugrov, I Yu; Dolgov, V V

    2016-03-01

    The article presents diagnostic of night paroxysmal hemoglobinuria. The night paroxysmal hemoglobinuria is an orphan disease characterized by absence of GPI-anchor on blood cells as a result of mutation of PIG-A gene on the short arm of X-chromosome. The particular proteins bounded with GPI-anchor implement function of defense from activation of components of complement and development of membrane-attacking complex. The erythrocytes exposed to destruction in bloodstream are among the most impacted. Therefore, one of the main signs of night paroxysmal hemoglobinuria is complement-depending intravascular hemolysis which indicators for a long time played a key role in diagnostic of night paroxysmal hemoglobinuria. The actual technique of diagnostic of night paroxysmal hemoglobinuria is flow cytometry. The analysis of night paroxysmal hemoglobinuria clone is recommended to patients with hemolysis of unclear genesis, thrombosis of cerebral and abdominal veins, thrombocytopenia and macrocytosis and also patients with AA, myelodysplastic syndrome, myelofibrosis. The international protocol recommended by the International Society of Clinical Cytometry (2010) is implemented to diagnose night paroxysmal hemoglobinuria. The original technique of evaluation of reticulocytes was developed with purpose to detect night paroxysmal hemoglobinuria clone. The high correlation was substantiated between size of night paroxysmal hemoglobinuria clone measured among reticulocytes according to proposed mode and night paroxysmal hemoglobinuria clone measured among granulocytes and monocytes detected according international standardized approach. PMID:27506106

  12. Bovine Postparturient Hemoglobinuria: A Review of the Literature

    PubMed Central

    Macwilliams, P. S.; Searcy, G. P.; Bellamy, J. E. C.

    1982-01-01

    Predisposing causes of bovine post-parturient hemoglobinuria are summarized along with suspected pathogeneses, clinical signs, laboratory findings, clinical management and early experimentation. PMID:17422195

  13. Eculizumab, bortezomib and kidney paired donation facilitate transplantation of a highly sensitized patient without vascular access.

    PubMed

    Lonze, B E; Dagher, N N; Simpkins, C E; Locke, J E; Singer, A L; Segev, D L; Zachary, A A; Montgomery, R A

    2010-09-01

    A 43-year-old patient with end-stage renal disease, a hypercoagulable condition and 100% panel reactive antibody was transferred to our institution with loss of hemodialysis access and thrombosis of the superior and inferior vena cava, bilateral iliac and femoral veins. A transhepatic catheter was placed but became infected. Access through a stented subclavian into a dilated azygos vein was established. Desensitization with two cycles of bortezomib was undertaken after anti-CD20 and IVIg were given. A flow-positive, cytotoxic-negative cross-match live-donor kidney at the end of an eight-way multi-institution domino chain became available, with a favorable genotype for this patient with impending total loss of a dialysis option. The patient received three pretransplant plasmapheresis treatments. Intraoperatively, the superior mesenteric vein was the only identifiable patent target for venous drainage. Eculizumab was administered postoperatively in the setting of antibody-mediated rejection and an inability to perform additional plasmapheresis. Creatinine remains normal at 6 months posttransplant and flow cross-match is negative. In this report, we describe the combined use of new agents (bortezomib and eculizumab) and modalities (nontraditional vascular access, splanchnic drainage of graft and domino paired donation) in a patient who would have died without transplantation. PMID:20636451

  14. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria

    PubMed Central

    Ricklin, Daniel; Huang, Yijun; Reis, Edimara S.; Chen, Hui; Ricci, Patrizia; Lin, Zhuoer; Pascariello, Caterina; Raia, Maddalena; Sica, Michela; Del Vecchio, Luigi; Pane, Fabrizio; Lupu, Florea; Notaro, Rosario; Resuello, Ranillo R. G.; DeAngelis, Robert A.; Lambris, John D.

    2014-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis due to the lack of CD55 and CD59 on affected erythrocytes. The anti-C5 antibody eculizumab has proven clinically effective, but uncontrolled C3 activation due to CD55 absence may result in opsonization of erythrocytes, possibly leading to clinically meaningful extravascular hemolysis. We investigated the effect of the peptidic C3 inhibitor, compstatin Cp40, and its long-acting form (polyethylene glycol [PEG]-Cp40) on hemolysis and opsonization of PNH erythrocytes in an established in vitro system. Both compounds demonstrated dose-dependent inhibition of hemolysis with IC50 ∼4 µM and full inhibition at 6 µM. Protective levels of either Cp40 or PEG-Cp40 also efficiently prevented deposition of C3 fragments on PNH erythrocytes. We further explored the potential of both inhibitors for systemic administration and performed pharmacokinetic evaluation in nonhuman primates. A single intravenous injection of PEG-Cp40 resulted in a prolonged elimination half-life of >5 days but may potentially affect the plasma levels of C3. Despite faster elimination kinetics, saturating inhibitor concentration could be reached with unmodified Cp40 through repetitive subcutaneous administration. In conclusion, peptide inhibitors of C3 activation effectively prevent hemolysis and C3 opsonization of PNH erythrocytes, and are excellent, and potentially cost-effective, candidates for further clinical investigation. PMID:24497537

  15. Eculizumab Treatment in a Patient with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy and Steroid-Refractory Acute Graft Versus Host Disease

    PubMed Central

    Fernández, Cristina; Lario, Ana; Cabrera, Rafael

    2015-01-01

    A 30-year-old man with acquired aplastic anemia underwent an HLA-identical bone marrow transplant. He developed a grade III acute graft versus host disease (GVHD) refractory to various lines of treatment. On post-transplant day 196, he was diagnosed with stem cell transplantation-associated thrombotic micro-angiopathy (HSCT-TMA) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later. After the first dose of eculizumab, the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization. Coinciding with the improved of HSCT-TMA, the patient presented a clear response to his acute GVHD with disappearance of the diarrhea and bilirubin normalization. He was discharged eight weeks after the start of treatment. Unfortunately, one month later, the patient was readmitted for a GVHD relapse and he died two weeks later by an acute respiratory distress syndrome. In our case, the rapid clinical and analytical response to early treatment with eculizumab supports the implication of the complement in HSCT-TMA and suggests that the drug has a beneficial effect when used as coadjuvant therapy in acute GVHD. PMID:26734129

  16. [Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome: a case report].

    PubMed

    Le Guyader, Maïlys; Pineau-Vincent, Fabienne; Lemaire, Pierre

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria is a rare clonal non-malignant disease, linked to an acquired PIG-A gene mutation. We report the case of 81 years old patient hospitalized for articular ache, swelling and temporal arteries' induration in which we diagnose PNH associated with refractory cytopenia with multilineage dysplasia. PMID:26744238

  17. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

    PubMed Central

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach. PMID:27110144

  18. Thrombotic microangiopathy and human immunodeficiency virus in the era of eculizumab.

    PubMed

    Jin, Anna; Boroujerdi-Rad, Laleh; Shah, Gaurang; Chen, Joline L T

    2016-08-01

    Thrombotic microangiopathies (TMAs) include thrombotic thromobocytopenic purpura and hemolytic uremic syndrome (HUS). Among these conditions, atypical HUS is now recognized to be a disease of alternative complement pathway dysregulation. Eculizumab is a recombinant humanized monoclonal antibody that binds to the complement protein C5 and prevents the cleavage of C5 to C5a and C5b. Eculizumab has been used as a novel treatment for complement-mediated TMA. We present a case of a patient with human immunodeficiency virus infection who developed TMA and was successfully treated with eculizumab. The effect of long-term treatment with this new medication is unknown, and further studies are needed to establish guidelines in the management of this condition. PMID:27478600

  19. Thrombotic microangiopathy and human immunodeficiency virus in the era of eculizumab

    PubMed Central

    Jin, Anna; Boroujerdi-Rad, Laleh; Shah, Gaurang; Chen, Joline L.T.

    2016-01-01

    Thrombotic microangiopathies (TMAs) include thrombotic thromobocytopenic purpura and hemolytic uremic syndrome (HUS). Among these conditions, atypical HUS is now recognized to be a disease of alternative complement pathway dysregulation. Eculizumab is a recombinant humanized monoclonal antibody that binds to the complement protein C5 and prevents the cleavage of C5 to C5a and C5b. Eculizumab has been used as a novel treatment for complement-mediated TMA. We present a case of a patient with human immunodeficiency virus infection who developed TMA and was successfully treated with eculizumab. The effect of long-term treatment with this new medication is unknown, and further studies are needed to establish guidelines in the management of this condition. PMID:27478600

  20. Case report: Benefits and challenges of long-term eculizumab in atypical hemolytic uremic syndrome.

    PubMed

    Cullinan, Noelle; Gorman, Kathleen Mary; Riordan, Michael; Waldron, Mary; Goodship, Timothy H J; Awan, Atif

    2015-06-01

    Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated against invasive meningococcal infection before beginning eculizumab therapy and take appropriate antibiotic prophylaxis during treatment, and we suggest that vaccine responses should be checked and followed annually. Clinicians need to maintain a high index of suspicion for invasive meningococcal disease. Neither vaccination nor antibiotic prophylaxis provides complete protection in patients on eculizumab therapy. The appropriate dosage of eculizumab needed to achieve remission in aHUS in the pediatric population is unknown. Having achieved remission in our patient, we monitor eculizumab and CH50 levels to evaluate ongoing blockade of the terminal complement cascade. Such information may help guide dosing intervals in the future. PMID:25941307

  1. Eculizumab for rescue of thrombotic microangiopathy in PM-Scl antibody-positive autoimmune overlap syndrome

    PubMed Central

    Thomas, Christie P.; Nester, Carla M.; Phan, Andrew C.; Sharma, Manisha; Steele, Amanda L.; Lenert, Petar S.

    2015-01-01

    A 46-year-old female with interstitial lung disease presented with proximal muscle weakness, worsening hypertension, microangiopathic hemolysis, thrombocytopenia and deteriorating renal function. She had no sclerodactyly, but had abnormal capillaroscopy. She tested positive for PM-Scl antibodies, and a renal biopsy showed an acute thrombotic microangiopathy consistent with scleroderma renal crisis (SRC). She failed to respond to corticosteroids, plasmapheresis and renin–angiotensin pathway inhibitors. She recovered quickly with the anti-C5 antibody, eculizumab. She had no genetic abnormalities associated with atypical hemolytic uremic syndrome except a DNA variant of unknown significance in C3. This case suggests that eculizumab may be effective for SRC. PMID:26613027

  2. Receivers

    NASA Astrophysics Data System (ADS)

    Donnelly, H.

    1983-07-01

    Before discussing Deep Space Network receivers, a brief description of the functions of receivers and how they interface with other elements of the Network is presented. Different types of receivers are used in the Network for various purposes. The principal receiver type is used for telemetry and tracking. This receiver provides the capability, with other elements of the Network, to track the space probe utilizing Doppler and range measurements, and to receive telemetry, including both scientific data from the onboard experiments and engineering data pertaining to the health of the probe. Another type of receiver is used for radio science applications. This receiver measures phase perturbations on the carrier signal to obtain information on the composition of solar and planetary atmospheres and interplanetary space. A third type of receiver utilizes very long baseline interferometry (VLBI) techniques for both radio science and spacecraft navigation data. Only the telemetry receiver is described in detail in this document. The integration of the Receiver-Exciter subsystem with other portions of the Deep Space Network is described.

  3. Receivers

    NASA Technical Reports Server (NTRS)

    Donnelly, H.

    1983-01-01

    Before discussing Deep Space Network receivers, a brief description of the functions of receivers and how they interface with other elements of the Network is presented. Different types of receivers are used in the Network for various purposes. The principal receiver type is used for telemetry and tracking. This receiver provides the capability, with other elements of the Network, to track the space probe utilizing Doppler and range measurements, and to receive telemetry, including both scientific data from the onboard experiments and engineering data pertaining to the health of the probe. Another type of receiver is used for radio science applications. This receiver measures phase perturbations on the carrier signal to obtain information on the composition of solar and planetary atmospheres and interplanetary space. A third type of receiver utilizes very long baseline interferometry (VLBI) techniques for both radio science and spacecraft navigation data. Only the telemetry receiver is described in detail in this document. The integration of the Receiver-Exciter subsystem with other portions of the Deep Space Network is described.

  4. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

    PubMed

    Ardissino, Gianluigi; Testa, Sara; Possenti, Ilaria; Tel, Francesca; Paglialonga, Fabio; Salardi, Stefania; Tedeschi, Silvana; Belingheri, Mirco; Cugno, Massimo

    2014-10-01

    Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission. PMID:24656451

  5. [Porto-hepatic thrombosis, revealing paroxysmal nocturnal hemoglobinuria, followed by regression induced by heparin therapy].

    PubMed

    Schmets, L; Hagège, H; Merlet, C; Zylberberg, H; Chousterman, M

    1993-01-01

    Budd-Chiari syndrome with or without portal thrombosis occurring during paroxysmal noctural hemoglobinuria is a complication with poor prognosis. We report the case of a 17-year-old woman with a double portal and hepatic venous thrombosis revealing a paroxysmal noctural hemoglobinuria and regressive with heparin. Our case suggests that the early diagnosis of the thrombosis with ultrasonography and Doppler, and rapidly initiated anticoagulant treatment may improve the prognosis of this disease. PMID:8125229

  6. Two case studies and a review of paroxysmal cold hemoglobinuria.

    PubMed

    Slemp, Stephanie N; Davisson, Suzanne M; Slayten, Jayanna; Cipkala, Douglas A; Waxman, Dan A

    2014-01-01

    Paroxysmal cold hemoglobinuria (PCH) is an acquired hemolytic anemia caused by immunoglobulin G (IgG) antibodies that sensitize red blood cells (RBCs) at cold temperatures by fixing complement to the RBCs causing intravascular hemolysis on rewarming. PCH usually appears in young children as recurrent high fevers, chills, and passage of red-brown urine. The diagnostic test for PCH is the Donath-Landsteiner test, an in vitro assay for biphasic hemolysis. Herein, we present 2 cases of PCH that occurred within 12 months of each other. We quickly diagnosed the second case and treated the patient successfully, in part due to our recognition of its characteristics based on the first case. PCH is a hemolytic anemia for which there is a specific diagnostic test; the timely recognition of this entity by physicians and laboratory staff will allow prompt, supportive therapy and will raise the odds of quick resolution of hemolysis. PMID:25051079

  7. A Case of Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab

    PubMed Central

    Thajudeen, B.; Sussman, A.; Bracamonte, E.

    2013-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. Eculizumab, a monoclonal complement C5 antibody which prevents the induction of the terminal complement cascade, has recently emerged as a therapeutic option for aHUS. We report a case of aHUS successfully treated with eculizumab. A 51-year-old male was admitted to the hospital following a mechanical fall. His past medical history was significant for rheumatic valve disease and mitral valve replacement; he was on warfarin for anticoagulation. A computed tomography scan of the head revealed a right-sided subdural hematoma due to coagulopathy resulting from a supratherapeutic international normalized ratio (INR). Following treatment with prothrombin complex concentrate to reverse the INR, urine output dropped and his serum creatinine subsequently increased to 247.52 μmol/l from the admission value of 70.72 μmol/l. Laboratory evaluation was remarkable for hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), low haptoglobin, and low complement C3. A renal biopsy was consistent with TMA, favoring a diagnosis of aHUS. Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH. Hemodialysis was terminated after 2.5 months due to improvement in urine output and solute clearance. The interaction between thrombin and complement pathway might be responsible for the pathogenesis of aHUS in this case. Eculizumab is an effective therapeutic agent in the treatment of aHUS. Early targeting of the complement system may modify disease progression and thus treat aHUS more effectively. PMID:24570684

  8. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

    PubMed Central

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-01-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was −0.99 standard deviation (SD) (range −4.01–+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

  9. Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape

    PubMed Central

    Mastellos, Dimitrios C; Ricklin, Daniel; Yancopoulou, Despina; Risitano, Antonio; Lambris, John D

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder associated with an acquired deficiency in glycophosphatidylinositol-anchor biosynthesis that renders erythrocytes susceptible to complement attack. Intravascular hemolysis via the membrane attack complex is a clinical hallmark of the disease, and C5 blockade is currently the only approved treatment for PNH. However, residual anemia is an emerging observation for many PNH patients receiving anti-C5 treatment. A range of complement-targeted therapeutic approaches, encompassing surface-directed inhibition of C3 convertases, blockade of membrane attack complex assembly or C3 interception using peptidic inhibitors, has yielded promising results and offers leverage for even more effective treatment of PNH. This article discusses recent advances in this rapidly evolving field, integrating critical perspectives from preclinical PNH models and diverse complement modulation strategies with genetic insights and therapy response profiles. It also evaluates the relative efficacy, limitations and benefits afforded by C3 or C5 inhibition in the context of PNH therapeutics. PMID:25213458

  10. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

    PubMed Central

    Hillmen, Peter; Muus, Petra; Röth, Alexander; Elebute, Modupe O; Risitano, Antonio M; Schrezenmeier, Hubert; Szer, Jeffrey; Browne, Paul; Maciejewski, Jaroslaw P; Schubert, Jörg; Urbano-Ispizua, Alvaro; de Castro, Carlos; Socié, Gérard; Brodsky, Robert A

    2013-01-01

    Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. PMID:23617322

  11. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab.

    PubMed

    Khan, Saif A; Al-Riyami, Dawood; Al-Mula Abed, Yasser W; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M

    2016-08-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  12. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab

    PubMed Central

    Khan, Saif A.; Al-Riyami, Dawood; Al-Mula Abed, Yasser W.; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M.

    2016-01-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR. PMID:27606122

  13. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria

    PubMed Central

    Shen, Wenyi; Clemente, Michael J.; Hosono, Naoko; Yoshida, Kenichi; Przychodzen, Bartlomiej; Yoshizato, Tetsuichi; Shiraishi, Yuichi; Miyano, Satoru; Ogawa, Seishi; Maciejewski, Jaroslaw P.; Makishima, Hideki

    2014-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic stem cells that is associated with hemolysis, marrow failure, and thrombophilia. PNH has been considered a monogenic disease that results from somatic mutations in the gene encoding PIGA, which is required for biosynthesis of glycosylphosphatidylinisotol-anchored (GPI-anchored) proteins. The loss of certain GPI-anchored proteins is hypothesized to provide the mutant clone with an extrinsic growth advantage, but some features of PNH argue that there are intrinsic drivers of clonal expansion. Here, we performed whole-exome sequencing of paired PNH+ and PNH– fractions on samples taken from 12 patients as well as targeted deep sequencing of an additional 36 PNH patients. We identified additional somatic mutations that resulted in a complex hierarchical clonal architecture, similar to that observed in myeloid neoplasms. In addition to mutations in PIGA, mutations were found in genes known to be involved in myeloid neoplasm pathogenesis, including TET2, SUZ12, U2AF1, and JAK2. Clonal analysis indicated that these additional mutations arose either as a subclone within the PIGA-mutant population, or prior to PIGA mutation. Together, our data indicate that in addition to PIGA mutations, accessory genetic events are frequent in PNH, suggesting a stepwise clonal evolution derived from a singular stem cell clone. PMID:25244093

  14. Thrombotic Microangiopathy as a Cause of Chronic Kidney Transplant Dysfunction: Case Report Demonstrating Successful Treatment with Eculizumab.

    PubMed

    Iqbal, Z; Wood, K; Carter, V; Goodship, T H; Brown, A L; Sheerin, N S

    2015-09-01

    Atypical hemolytic uremic syndrome is a rare disease associated with genetic or acquired defects in complement regulation which frequently leads to renal failure. Disease often recurs early after kidney transplantation, leading to a rapid irreversible loss of function. Extrarenal features, such as hemolysis and thrombocytopenia, may not always occur, and diagnosis is made by demonstrating the classic features of thrombotic microangiopathy on renal biopsy. Eculizumab, a terminal complement inhibitor, has been used successfully to treat fulminant early recurrent disease after transplantation. We describe a case of disease recurrence presenting in the second year after transplantation with a gradual decline in function and the first report of eculizumab treatment for chronic thrombotic microangiopathy in a transplanted kidney. The resultant diagnostic challenges and successful response to eculizumab in this setting are discussed. PMID:26361694

  15. Abnormality of glycophorin-alpha on paroxysmal nocturnal hemoglobinuria erythrocytes.

    PubMed Central

    Parker, C J; Soldato, C M; Rosse, W F

    1984-01-01

    To investigate the greater enzymatic activity of the alternative pathway convertase (and the subsequent greater fixation of C3b) on paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes, we have examined the topography of binding of C3b to PNH and normal erythrocytes. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, the alpha-chain of C3b was found to bind via predominantly ester bonds to free hydroxyl groups on glycophorin-alpha, the major erythrocyte sialoglycoprotein. The pattern of binding of nascent C3b was the same for normal and PNH erythrocytes. Thus, although C3b binding to a different membrane constituent did not appear to account for the greater enzymatic activity of the alternative pathway convertase when affixed to PNH erythrocytes, it seemed possible that the glycoproteins to which C3b bound might be qualitatively abnormal on the PNH cells, and that structural differences in these molecules might impose modifications in the enzyme-substrate interactions of the alternative pathway convertase. Using methods for radiolabeling both protein and carbohydrate residues, we therefore compared the electrophoretic pattern of the cell-surface glycoproteins on PNH and normal erythrocytes. The glycophorin-alpha dimer was found to be qualitatively abnormal on the PNH cells as evidenced by its greater susceptibility to trypsin-mediated proteolysis. In addition, the abnormal erythrocytes from patients with PNH had fewer periodate oxidizable constituents than did normal erythrocytes, indicating a relative deficiency of cell-surface sialic acid. These investigations suggest that abnormalities in membrane glycoproteins may underlie the aberrant interactions of complement with the hematopoietic elements of PNH. Images PMID:6231312

  16. Impaired phagocyte responses to lipopolysaccharide in paroxysmal nocturnal hemoglobinuria.

    PubMed Central

    Duchow, J; Marchant, A; Crusiaux, A; Husson, C; Alonso-Vega, C; De Groote, D; Neve, P; Goldman, M

    1993-01-01

    Bone marrow-derived cells from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH) show a defect in the expression of phosphatidylinositol-anchored membrane proteins, including the CD14 molecule. Blocking experiments with anti-CD14 monoclonal antibodies have shown that lipopolysaccharide (LPS)-induced tumor necrosis factor alpha production by monocytes depends on the interaction between CD14 and a complex formed by LPS and LPS-binding protein. We used a whole-blood model to examine the LPS-induced production of tumor necrosis factor alpha and interleukin-6 in PNH patients and healthy volunteers. At low endotoxin concentrations (1 ng/ml), PNH patients displayed a marked defect in the production of both cytokines, whereas at high LPS concentrations (100 ng/ml), cytokine production was similar to that in healthy volunteers. Using flow cytometry, we also studied the expression of the adhesion molecules Mac-1 (CD11b/CD18) and ICAM-1 (CD54) by monocytes and granulocytes after LPS stimulation. Compared with phagocytes from healthy volunteers, CD14-deficient cells showed poor Mac-1 and ICAM-1 upregulation when whole blood was stimulated with LPS (1 ng/ml), whereas their response to higher LPS doses (100 and 1,000 ng/ml) was essentially normal. The importance of the CD14 molecule in the activation of phagocytes by low LPS concentrations was confirmed by the inhibitory effect of an anti-CD14 antibody both in healthy volunteers and in PNH patients. Since these patients produce the soluble form of the CD14 molecule, these data suggest that soluble CD14 could play a role in phagocyte responses to LPS. We conclude that, in whole blood, phagocytes from PNH patients show impaired responsiveness to LPS and this phenomenon is most probably related to their defect in expression of membrane CD14. PMID:7691746

  17. Use of Eculizumab in Atypical Hemolytic Uremic Syndrome, Complicating Systemic Lupus Erythematosus.

    PubMed

    Bermea, Rene S; Sharma, Niharika; Cohen, Kenneth; Liarski, Vladimir M

    2016-09-01

    Atypical hemolytic uremic syndrome is characterized by the presence of thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. In this report, we describe two patients with systemic lupus erythematosus who presented with findings compatible with atypical hemolytic uremic syndrome, complicated by acute kidney injury that was refractory to conventional therapies. Both patients exhibited a response to eculizumab, a monoclonal antibody to complement protein C5, with stabilization of their platelet count. On 1-year follow-up from their initial presentation, their hematologic disease remained in remission without recurrence. PMID:27556240

  18. 9 CFR 311.10 - Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Anaplasmosis, anthrax, babesiosis, bacillary hemoglobinuria in cattle, blackleg, bluetongue, hemorrhagic septicemia, icterohematuria in sheep, infectious bovine rhinotracheitis, leptospirosis, malignant epizootic catarrh, strangles, purpura hemorrhagica, azoturia, infectious...

  19. Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

    PubMed Central

    Ring, Troels; Pedersen, Birgitte Bang; Salkus, Giedrius; Goodship, Timothy H.J.

    2015-01-01

    IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement. PMID:26413271

  20. Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

    PubMed

    Ring, Troels; Pedersen, Birgitte Bang; Salkus, Giedrius; Goodship, Timothy H J

    2015-10-01

    IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement. PMID:26413271

  1. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS

    PubMed Central

    Cofiell, Roxanne; Kukreja, Anjli; Bedard, Krystin; Yan, Yan; Mickle, Angela P.; Ogawa, Masayo; Bedrosian, Camille L.

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening disease characterized by uncontrolled complement activation, systemic thrombotic microangiopathy (TMA), and vital organ damage. We evaluated the effect of terminal complement blockade with the anti-C5 monoclonal antibody eculizumab on biomarkers of cellular processes involved in TMA in patients with aHUS longitudinally, during up to 1 year of treatment, compared with in healthy volunteers. Biomarker levels were elevated at baseline in most patients, regardless of mutational status, plasma exchange/infusion use, platelet count, or lactate dehydrogenase or haptoglobin levels. Eculizumab reduced terminal complement activation (C5a and sC5b-9) and renal injury markers (clusterin, cystatin-C, β2-microglobulin, and liver fatty acid binding protein-1) to healthy volunteer levels and reduced inflammation (soluble tumor necrosis factor receptor-1), coagulation (prothrombin fragment F1+2 and d-dimer), and endothelial damage (thrombomodulin) markers to near-normal levels. Alternative pathway activation (Ba) and endothelial activation markers (soluble vascular cell adhesion molecule-1) decreased but remained elevated, reflecting ongoing complement activation in aHUS despite complete terminal complement blockade. These results highlight links between terminal complement activation and inflammation, endothelial damage, thrombosis, and renal injury and underscore ongoing risk for systemic TMA and progression to organ damage. Further research regarding underlying complement dysregulation is warranted. This trial was registered at www.clinicaltrials.gov as #NCT01194973. PMID:25833956

  2. [Efficacy of eculizumab in a case of pregnancy-associated aHUS].

    PubMed

    Cravero, Raffaella; Ardissino, Gianluigi; Colageo, Umberto; Staffa, Piernicola; Bruschetta, Elena; Maroni, Serena; Karvela, Eirini; Spagarino, Ermanno; Ruggeri, Velia; Jura, Roberto

    2016-01-01

    Pregnancy-associated thrombotic microangiopathy (TMA) is a rare condition, but it is burdened by a significant perinatal and maternal morbidity as well as mortality. We describe the case of a 33-year-old woman, who developed a TMA at the 36th week of gestation characterized by increased LDH, haptoglobin consumption, schistocytes, thrombocytopenia and acute renal failure requiring dialysis. There were not gestational hypertension nor proteinuria until the day of hospitalization. ADAMTS 13 deficiency was ruled out and the patient did not have diarrhea. She was initially treated with caesarean section, plasma infusion and plasmapheresis with no benefit. Five days after the onset of TMA, a temptative diagnosis of atypical uremic syndrome (aHUS) was made and the patient was switched to eculizumab. Antibiotic prophylaxis and anti-meningococcal A,B, C, W135 and Y vaccination was performed. TMA rapidly resolved and renal function completely recovered. The newborn had a normal perinatal course. A complement dysregulation was ruled out by testing for mutations on CFH, CFHR3-R1, CFI, MCP, CFB, C3 and for anti CFH antibodies. In conclusion the differential diagnosis of aHUS with HELLP syndrome is often not straightforward. The severity and persistence of TMA, the high mortality associated to peripartum TMA and the risk for irreversible kidney failure require an early therapeutic decision as to the use of eculizumab. PMID:27545639

  3. Atypical Hemolytic Uremic Syndrome and Chronic Ulcerative Colitis Treated with Eculizumab

    PubMed Central

    Webb, Tennille N.; Griffiths, Heidi; Miyashita, Yosuke; Bhatt, Riha; Jaffe, Ronald; Moritz, Michael; Hofer, Johannes; Swiatecka-Urban, Agnieszka

    2016-01-01

    Background Hemolytic-uremic syndrome (HUS) presents with hemolytic anemia, thrombocytopenia, and thrombotic microangiopathy of the kidney and usually results from Shiga-toxin induced activation of the alternative complement pathway. Gastroenteritis is a common feature of the Shiga-toxin producing Escherichia coli HUS, referred to as STEC-HUS. An inherited or acquired complement dysregulation may lead to HUS referred to as non-STEC or atypical (a)HUS. Although gastroenteritis is not a common presentation of aHUS, some patients develop ischemic colitis and may be misdiagnosed as acute appendicitis or acute ulcerative colitis (UC). Case Diagnosis –Treatment We present a patient with low circulating complement (C) 3 levels who developed aHUS in the course of chronic active UC. Resolution of renal and gastrointestinal manifestations in response to treatment with eculizumab, a humanized monoclonal antibody against terminal C5 protein suggests the role of alternative complement in the pathogenesis of both, aHUS and UC. Conclusion This case illustrates that dysregulation of the alternative complement pathway may manifest in other organs besides the kidney and that the circulating C3 levels do not correlate with the disease activity or the clinical response to eculizumab. PMID:27135055

  4. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity.

    PubMed

    Shapiro, Roman; Chin-Yee, Ian; Lam, Selay

    2015-11-01

    Severe cold agglutinin disease with hemodynamic compromise requires rapid stabilization of the autoimmune hemolytic anemia as a bridge to the immunosuppressive effect of rituximab. Herein, we describe eculizumab treatment of severe complement-mediated hemolysis in a patient whose hemodynamic status deteriorated in spite of supportive blood transfusions and therapeutic plasma exchange. PMID:26576277

  5. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies

    PubMed Central

    Licht, Christoph; Greenbaum, Larry A; Muus, Petra; Babu, Sunil; Bedrosian, Camille L; Cohen, David J; Delmas, Yahsou; Douglas, Kenneth; Furman, Richard R; Gaber, Osama A; Goodship, Timothy; Herthelius, Maria; Hourmant, Maryvonne; Legendre, Christophe M; Remuzzi, Giuseppe; Sheerin, Neil; Trivelli, Antonella; Loirat, Chantal

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m2 or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up. PMID:25651368

  6. Cerebral venous thrombosis presenting with intracerebral hemorrhage in a patient with paroxysmal nocturnal hemoglobinuria

    PubMed Central

    Shrestha, Gentle Sunder; Poudyal, Bishesh Sharma; Sedain, Gopal; Mahmud, Khandokar Imran; Acharya, Niranja

    2016-01-01

    Cerebral venous thrombosis (CVT) is an uncommon cause of stroke. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare type of hemolytic anemia, frequently associated with thrombophilia. PNH may rarely present with CVT. Approximately, one-third of the patients with CVT develop cerebral hemorrhage. Here, we present a rare combination of CVT presenting with intracerebral hemorrhage in a patient with PNH. High index of suspicion is needed to avoid misdiagnosis. Patient was successfully managed with anticoagulation therapy. PMID:27076714

  7. Eculizumab Injection

    MedlinePlus

    ... develop a meningococcal infection (an infection that may affect the covering of the brain and spinal cord and/or may spread through the bloodstream) during your treatment or for some time afterward. Meningococcal infections may cause death in a ...

  8. Eculizumab Injection

    MedlinePlus

    ... your child's doctor about giving your child these vaccinations and any other vaccinations your child needs.if you are being treated ... your condition may cause too many red blood cells to break down after you stop ... breathing; swelling in the arms or legs; or any other unusual symptoms.

  9. Eculizumab for Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: A Single-Center Experience.

    PubMed

    Yelken, B; Arpalı, E; Görcin, S; Kocak, B; Karatas, C; Demiralp, E; Turkmen, A

    2015-01-01

    Antibody-mediated rejection (AMR) is responsible for up to 20%-30% of acute rejection episodes after kidney transplantation. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, a monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present 8 cases that were resistant to conventional therapy and in which eculizumab was given as a salvage treatment. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss. PMID:26293046

  10. Frequency of paroxysmal nocturnal hemoglobinuria in patients attended in Belém, Pará, Brazil

    PubMed Central

    de Brito Junior, Lacy Cardoso; Cardoso, Maria do Socorro de Oliveira; Rocha, Euzamar Gaby; Anijar, Herika; Cunha, Mariana; Saraiva, João Carlos Pina

    2011-01-01

    Background Paroxysmal nocturnal hemoglobinuria is a hematological disease with complex physiopathology. It is genetically characterized by a somatic mutation in the PIG-A gene (phosphatidylinositol glycan anchor biosynthesis, class A), in which the best known antigens are DAF (decay accelerating factor or CD55) and MIRL (membrane inhibitor of reactive lysis or CD59). Objective To determine the frequency of paroxysmal nocturnal hemoglobinuria in patients attended at the HEMOPA foundation from November 2008 to July 2009. Method Thirty patients, with ages ranging from two to 79 years old and suspected of having paroxysmal nocturnal hemoglobinuria were examined. All patients were immunophenotyped by flow cytometry for the CD5, CD59, CD16 and CD45 antigens. Results Paroxysmal nocturnal hemoglobinuria was identified in nine of the thirty patients investigated. Another 3 cases had inconclusive results with CD59-negative labeling only for neutrophils. The highest frequency of paroxysmal nocturnal hemoglobinuria patients (7/9) and inconclusive cases (2/3) were between 19 years old and 48 years old, with a median of 28 years. Conclusion These results show the importance of flow cytometry to identify cases in which patients are deficient in only one antigen (CD59). PMID:23284241

  11. Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response

    PubMed Central

    Deuel, J W; Schaer, C A; Boretti, F S; Opitz, L; Garcia-Rubio, I; Baek, J H; Spahn, D R; Buehler, P W; Schaer, D J

    2016-01-01

    Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe2+) to ferric Hb(Fe3+), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria. PMID:26794659

  12. Thrombolytic therapy is effective in paroxysmal nocturnal hemoglobinuria: a series of nine patients and a review of the literature

    PubMed Central

    Araten, David J.; Notaro, Rosario; Thaler, Howard T; Kernan, Nancy; Boulad, Farid; Castro-Malaspina, Hugo; Small, Trudy; Scaradavou, Andromachi; Magnan, Heather; Prockop, Susan; Chaffee, Sara; Gonsky, Jason; Thertulien, Raymond; Tarquini, Roberto; Luzzatto, Lucio

    2012-01-01

    Background Thrombosis is the major risk factor for death in patients with paroxysmal nocturnal hemoglobinuria. Previous case reports indicate that venous thrombosis in patients with paroxysmal nocturnal hemoglobinuria is amenable to thrombolysis. Design and Methods We reviewed the outcome of thrombolytic therapy for patients with paroxysmal nocturnal hemoglobinuria who had thromboses refractory to anticoagulation at our institutions. Results In this study of 41 patients who had at least one thrombotic event, we confirmed a very high incidence of recurrence despite anticoagulation. Nine patients with thrombosis were regarded as eligible for administration of intravenous tissue plasminogen activator, which was effective in reversing thrombi in all of 15 occasions in which it was given. Serious hemorrhagic complications developed in three cases. At last follow-up visit, of the nine patients treated, three had died, and six were in very good to excellent condition in terms of clinical outcome and radiological findings. The only patient in whom thrombolysis may have contributed to a fatal outcome also had complications of “heparin induced thrombocytopenia with thrombosis”, which we diagnosed in three additional patients. In our review of the literature, nine out of 15 patients treated with thrombolysis have had a good outcome. Conclusions Although it is associated with a significant but manageable risk of bleeding, systemic thrombolysis is a highly effective treatment for reversing venous thromboses in patients with paroxysmal nocturnal hemoglobinuria. PMID:22133780

  13. Reduced-intensity stem cell allografting for PNH patients in the eculizumab era: The Mexican experience.

    PubMed

    Schcolnik-Cabrera, Alejandro; Labastida-Mercado, Nancy; Galindo-Becerra, Laura Samantha; Gomez-Almaguer, David; Herrera-Rojas, Miguel Angel; Ruiz-Delgado, Guillermo Jose; Ruiz-Arguelles, Guillermo José

    2015-06-01

    Background Paroxysmal nocturnal haemoglobinuria (PNH) presents as two major entities: the classical form, predominantly haemolytic and a secondary type with marrow failure and resultant aplastic anaemia (AA-PNH). Currently, the treatment of choice of the haemolytic variant is eculizumab; however, the most frequent form of PNH in México is AA-PNH. Patients and methods Six consecutive AA-PNH patients with HLA-identical siblings were allografted in two institutions in México, employing a reduced-intensity conditioning regimen for stem cell transplantation (RIST) conducted on an outpatient basis. Results Median age of the patients was 37 years (range 25-48). The patients were given a median of 5.4 × 10(6)/kg allogeneic CD34(+) cells, using 1-3 apheresis procedures. Median time to achieve above 0.5 × 10(9)/l granulocytes was 21 days, whereas median time to achieve above 20 × 10(9)/l platelets was 17 days. Five patients are alive for 330-3150 days (median 1437) after the allograft. The 3150-day overall survival is 83.3%, whereas median survival has not been reached, being above 3150 days. Conclusion We have shown that hypoplastic PNH patients can be allografted safely using RIST and that the long-term results are adequate, the cost-benefit ratio of this treatment being reasonable. Additional studies are needed to confirm the usefulness of RIST in the treatment of AA-PNH. PMID:25148373

  14. Refractory IgG Warm Autoimmune Hemolytic Anemia Treated with Eculizumab: A Novel Application of Anticomplement Therapy

    PubMed Central

    Ma, Kim; Caplan, Stephen

    2016-01-01

    Warm autoimmune hemolytic anemia (wAIHA) is the most common form of AIHA, with corticosteroids in first-line treatment resulting in a 60–80% response rate. Atypical wAIHA and IgG plus complement mediated disease have a higher treatment failure rate and higher recurrence rate. We report a case of severe wAIHA secondary to Waldenström macroglobulinemia with life threatening intravascular hemolysis refractory to prednisone, rituximab, splenectomy, and plasmapheresis. A four-week treatment of eculizumab in this heavily pretreated patient resulted in a sustained increase in hemoglobin and transfusion independence, suggesting a role for complement inhibition in refractory wAIHA. PMID:27092282

  15. [The C5 gene polymorphism in patients with PNH].

    PubMed

    Nishimura, Jun-Ichi; Kanakura, Yuzuru

    2015-02-01

    This review is a commentary on an article entitled "Genetic variants in C5 and poor response to eculizumab" (N Engl J Med. 2014; 370: 632-639). The molecular basis for the poor response to eculizumab in Japanese patients is unclear. Of 345 Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) who received eculizumab, 11 showed a poor response. All 11 had a single missense C5 heterozygous mutation, c.2654 G>A, which predicts the polymorphism p.Arg885His. The prevalence of this mutation among patients with PNH (3.2%) was similar to that in healthy Japanese persons (3.5%). This polymorphism was also identified in a Han Chinese population. Non-mutant and mutant C5 both caused hemolysis in vitro, but only non-mutant C5 bound to and was blocked by eculizumab. In vitro hemolysis due to non-mutant and mutant C5 was completely blocked by N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab. The functional capacity of the C5 polymorphism p.Arg885His, together with its failure to undergo blockade by eculizumab, accounts for the poor response to this agent in patients who carry this mutation. PMID:25765788

  16. Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm

    PubMed Central

    Fraiman, Yarden S; Cuka, Nathan; Batista, Denise; Vuica-Ross, Milena; Moliterno, Alison R

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure, is associated with mutations in the PIG-A gene, resulting in a deficiency of glycosylphosphatidylinositol-anchored proteins. Many hypotheses have been posed as to whether PNH and PIG-A mutations result in an intrinsic survival benefit of CD55−/CD59− cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment. Recent data have identified the concurrence of PIG-A mutations with additional genetic mutations associated with myeloproliferative disorders, suggesting that some presentations of PNH are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes. We report for the first time in the literature the development of clinically significant PNH in a patient with JAK2V617F-negative, CALR-positive essential thrombocythemia, providing further support to the hypothesis that the development of PNH is associated with the accumulation of multiple genetic mutations that create an intrinsic survival benefit for clonal expansion. This case study additionally highlights the utility of genomic testing in diagnosis and the understanding of disease progression in the clinical setting. PMID:27313483

  17. Terminal Complement Blockade after Hematopoietic Stem Cell Transplantation Is Safe without Meningococcal Vaccination.

    PubMed

    Jodele, Sonata; Dandoy, Christopher E; Danziger-Isakov, Lara; Myers, Kasiani C; El-Bietar, Javier; Nelson, Adam; Wallace, Gregory; Teusink-Cross, Ashley; Davies, Stella M

    2016-07-01

    Eculizumab inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy (TMA) in patients with atypical hemolytic uremic syndrome and is now used as a first-line therapy in these diseases. Eculizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) because of an increased risk of meningococcal infections in persons without adequate functional complement. Administration of meningococcal vaccine is required at least 2 weeks before administering the first dose of eculizumab, and this advice is included in the product label. Eculizumab use for treatment of TMA in hematopoietic stem cell transplantation (HSCT) recipients brings a significant dilemma regarding REMS required meningococcal vaccination. TMA after HSCT usually occurs within the first 100 days after transplantation when patients are severely immunocompromised and are not able to mount a response to vaccines. We evaluated 30 HSCT recipients treated with eculizumab for high-risk TMA without meningococcal vaccine. All patients received antimicrobial prophylaxis adequate for Neisseria meningitides during eculizumab therapy and for 8 weeks after discontinuation of the drug. Median time to TMA diagnosis was 28 days after transplant (range, 13.8 to 48.5). Study subjects received a median of 14 eculizumab doses (range, 2 to 38 doses) for HSCT-associated TMA therapy. There were no incidences of meningococcal infections. The incidences of bacterial and fungal bloodstream infections were similar in patients treated with eculizumab (n = 30) as compared with those with HSCT-associated TMA who did not receive any complement blocking therapy (n = 39). Our data indicate that terminal complement blockade in the early post-transplant period can be performed without meningococcal vaccination while using appropriate antimicrobial prophylaxis until complement

  18. Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-

    PubMed Central

    Perdigones, Nieves; Morales, Mariela; Mason, Philip; Bessler, Monica

    2014-01-01

    We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   ( G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene.  PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( GPI)  anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been selected because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode. PMID:25713697

  19. Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-.

    PubMed

    Perdigones, Nieves; Morales, Mariela; Mason, Philip; Bessler, Monica

    2014-01-01

    We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   ( G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene.  PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( GPI)  anchor synthesis. Two GPI anchored red cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been selected because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD A- red cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDA- at the time of the hemolytic episode. PMID:25713697

  20. The Phenotype of a Germline Mutation in PIGA: The Gene Somatically Mutated in Paroxysmal Nocturnal Hemoglobinuria

    PubMed Central

    Johnston, Jennifer J.; Gropman, Andrea L.; Sapp, Julie C.; Teer, Jamie K.; Martin, Jodie M.; Liu, Cyndi F.; Yuan, Xuan; Ye, Zhaohui; Cheng, Linzhao; Brodsky, Robert A.; Biesecker, Leslie G.

    2012-01-01

    Phosphatidylinositol glycan class A (PIGA) is involved in the first step of glycosylphosphatidylinositol (GPI) biosynthesis. Many proteins, including CD55 and CD59, are anchored to the cell by GPI. Loss of CD55 and CD59 on erythrocytes causes complement-mediated lysis in paroxysmal nocturnal hemoglobinuria (PNH), a disease that manifests after clonal expansion of hematopoietic cells with somatic PIGA mutations. Although somatic PIGA mutations have been identified in many PNH patients, it has been proposed that germline mutations are lethal. We report a family with an X-linked lethal disorder involving cleft palate, neonatal seizures, contractures, central nervous system (CNS) structural malformations, and other anomalies. An X chromosome exome next-generation sequencing screen identified a single nonsense PIGA mutation, c.1234C>T, which predicts p.Arg412∗. This variant segregated with disease and carrier status in the family, is similar to mutations known to cause PNH as a result of PIGA dysfunction, and was absent in 409 controls. PIGA-null mutations are thought to be embryonic lethal, suggesting that p.Arg412∗ PIGA has residual function. Transfection of a mutant p.Arg412∗ PIGA construct into PIGA-null cells showed partial restoration of GPI-anchored proteins. The genetic data show that the c.1234C>T (p.Arg412∗) mutation is present in an affected child, is linked to the affected chromosome in this family, is rare in the population, and results in reduced, but not absent, biosynthesis of GPI anchors. We conclude that c.1234C>T in PIGA results in the lethal X-linked phenotype recognized in the reported family. PMID:22305531

  1. A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America.

    PubMed

    Yu, Fan; Du, Yali; Han, Bing

    2016-06-01

    To accurately analyze the clinical characteristics of paroxysmal nocturnal hemoglobinuria (PNH) in different ethnic backgrounds, we retrieved all retrospective studies on clinical characteristics of PNH with a median follow-up period >60 months published after 2000, analyzed the clinical characteristics of PNH patients in Asia and European/America, and statistically compared enumeration data in these studies. We included 1665 patients in this analysis. The proportion of female patients in Asia was significantly lower than that in Europe/America (P = 0.000). Incidence rates of hemoglobinuria and thromboembolism in Asia were significantly lower than in Europe/America (both P values were 0.000). Within the subgroups of patients with thromboembolism, Asian patients had a higher proportion of arterial thrombosis while Western patients had a higher proportion of abdominal venous thrombosis. Bone marrow failure was not clearly defined in most studies. The proportion of patients with pancytopenia was higher in China than in France (P = 0.048). The total death rates were similar in both ethnic groups (P > 0.05). In Europe/America the major cause of death was thromboembolism and in Asian countries was serious infections. Differences in population characteristics of PNH patients among different ethnic groups indicate the possibility of differential pathogenesis and may be informative for treatment decisions. PMID:27059871

  2. The study on RBC characteristic in paroxysmal nocturnal hemoglobinuria (PNH) patients using common path interferometric quantitative phase microscopy

    NASA Astrophysics Data System (ADS)

    Park, Byung Jun; Won, Youngjae; Kim, Byungyeon; Lee, Seungrag

    2016-03-01

    We have studied the RBC membrane properties between a normal RBC and a RBC in Paroxysrnal nocturnal hemoglobinuria (PNH) patient using common path interferometric quantitative phase microscopy (CPIQPM). CPIQPM system has provided the subnanometer optical path length sensitivity on a millisecond. We have measured the dynamic thickness fluctuations of a normal RBC membrane and a RBC membrane in PNH patient over the whole cell surface with CPIQPM. PNH is a rare and serious disease of blood featured by destruction of red blood cells (RBCs). This destruction happens since RBCs show the defect of protein which protects RBCs from the immune system. We have applied CPIQPM to study the characteristic of RBC membrane in PNH patient. We have shown the morphological shape, volume, and projected surface for both different RBC types. The results have showed both RBCs had the similar shape with donut, but membrane fluctuations in PNH patient was shown to reveal the difference of temporal properties compared with a normal RBC. In order to demonstrate the practical tool of the CPIQPM technique, we have also obtained the time series thickness fluctuation outside a cell.

  3. High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study.

    PubMed

    Stebler, C; Tichelli, A; Dazzi, H; Gratwohl, A; Nissen, C; Speck, B

    1990-12-01

    In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r-HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r-HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO. PMID:2226680

  4. CALUTRON RECEIVER

    DOEpatents

    Barnes, S.W.

    1959-06-16

    An improved receiver and receiver mount for calutrons are described. The receiver can be manipulated from outside the tank by a single control to position it with respect to the beam. A door can be operated exteriorly also to prevent undesired portions of the beam from entering the receiver. The receiver has an improved pocket which is more selective in the ions collected. (T.R.H.)

  5. CALUTRON RECEIVER

    DOEpatents

    Brunk, W.O.

    1959-09-29

    A description is given for an improved calutron receiver having a face plate lying at an angle to the direction of the entering ion beams but having an opening, the plane of which is substantially perpendicular to that of the entering ion beams. By so positioning the opening in the receiver, the effective area through which the desired material may enter the receiver is increased, and at the same time the effective area through which containattng material may enter the receiver is reduced.

  6. CALUTRON RECEIVER

    DOEpatents

    York, H.F.

    1959-07-01

    A receiver construction is presented for calutrons having two or more ion sources and an individual receiver unit for each source. Design requirements dictate that the face plate defining the receiver entrance slots be placed at an angle to the approaching beam, which means that ions striking the face plate are likely to be scattcred into the entrance slots of other receivers. According to the present invention, the face plate has a surface provided with parallel ridges so disposed that one side only of each ridge's exposed directly to the ion beam. The scattered ions are directed away from adjacent receivers by the ridges on the lace plate.

  7. Radio receivers

    NASA Astrophysics Data System (ADS)

    Bankov, V. N.; Barulin, L. G.; Zhodzishskii, M. I.; Malyshev, I. V.; Petrusinskii, V. V.

    The book is concerned with the design of microelectronic radio receivers and their components based on semiconductor and hybrid integrated circuits. Topics discussed include the hierarchical structure of radio receivers, the synthesis of structural schemes, the design of the principal functional units, and the design of radio receiver systems with digital signal processing. The discussion also covers the integrated circuits of multifunctional amplifiers, analog multipliers, charge-transfer devices, frequency filters, piezoelectronic devices, and microwave amplifiers, filters, and mixers.

  8. CALUTRON RECEIVERS

    DOEpatents

    Lofgren, E.J.

    1958-09-01

    Improvements are described in isotope separation devices of the calutron type and, in particular, deals with a novel caiutron receiver which passes the optimum portions of the ion beam to a collecting chamber. In broad aspects the receiver provides means for pass delimited pontion of the beam and an elongated collecting pocket disposed to receive ions passed by the beam delimiting means. The collecting pocket is transversely partitioned into a plurality of ion receiving compartments respectively defined by a corresponding plurality of separately removable liner elements.

  9. CALUTRON RECEIVERS

    DOEpatents

    Schmidt, F.H.; Stone, K.F.

    1958-09-01

    S>This patent relates to improvements in calutron devices and, more specifically, describes a receiver fer collecting the ion curreot after it is formed into a beam of non-homogeneous isotropic cross-section. The invention embodies a calutron receiver having an ion receiving pocket for separately collecting and retaining ions traveling in a selected portion of the ion beam and anelectrode for intercepting ions traveling in another selected pontion of the ion beam. The electrode is disposed so as to fix the limit of one side of the pontion of the ion beam admitted iato the ion receiving pocket.

  10. CALUTRON RECEIVERS

    DOEpatents

    MacKenzie, K.R.

    1958-09-16

    A novel calutron receiver is described for collecting the constituent material of two closely adjacent selected portions of an ion beam in separate compartments. The receiver is so conntructed that ion scatter and intermixing of the closely adjacent beam portions do nnt occur when the ions strike the receiver structure, and the beam is sharply separated Into the two compartments. In essence, these desirable results are achieved by inclining the adjoining wall of one compartment with respect to the approaching ions to reduce possible rebounding of ions from the compartment into the adjacent compartment.

  11. Paroxysmal cold hemoglobinuria (PCH)

    MedlinePlus

    ... the urine. PCH has been linked to secondary syphilis, tertiary syphilis, and other viral or bacterial infections. Sometimes the ... help. For example, if PCH is caused by syphilis, symptoms may get better when the syphilis is ...

  12. Paroxysmal Nocturnal Hemoglobinuria (PNH)

    MedlinePlus

    ... Blood consists of blood cells floating in plasma . Plasma is mostly made of water. It also includes salts, proteins, hormones, minerals, vitamins and other nutrients and chemicals your body needs. What are the 3 Basic Types of Blood Cells? Red blood cells ( ...

  13. Paroxysmal cold hemoglobinuria (PCH)

    MedlinePlus

    ... condition. Bilirubin levels are high in blood and urine Complete blood count (CBC) shows anemia. Coombs test is negative. Donath-Landsteiner test is positive. Level of hemoglobin is increased during attacks. Lactate ...

  14. Paroxysmal nocturnal hemoglobinuria (PNH)

    MedlinePlus

    ... break down too early. The red cells leak hemoglobin into the blood, which can pass into the ... the breakdown of red blood cells and that hemoglobin is being released into the body's circulation and ...

  15. Paroxysmal nocturnal hemoglobinuria (PNH)

    MedlinePlus

    ... morning. The disease can affect people of any age. It may be associated with aplastic anemia , myelodysplastic syndrome, or acute myelogenous leukemia . Risk factors, except for prior aplastic anemia, are not known.

  16. Red Kidney: Kidney Transplant From a Deceased Donor Who Received Massive Blood Transfusion During Cardiopulmonary Bypass.

    PubMed

    Bell, Richard; Hanif, Faisal; Prasad, Padmini; Ahmad, Niaz

    2016-06-01

    Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function. PMID:26030717

  17. CALUTRON RECEIVER

    DOEpatents

    Barnes, S.W.

    1959-08-25

    An improvement in a calutron receiver for collecting the isotopes ts described. The electromagnetic separation of the isotopes produces a mass spectrum of closely adjacent beams of ions at the foci regions, and a dividing wall between the two pockets is arranged at an angle. Substantially all of the tons of the less abundant isotope enter one of the pockets and strike one side of the wall directly, while substantially none of the tons entering the other pocket strikes the wall directly.

  18. Radiation receiver

    DOEpatents

    Hunt, A.J.

    1983-09-13

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles. 5 figs.

  19. Radiation receiver

    DOEpatents

    Hunt, Arlon J.

    1983-01-01

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles.

  20. Expression and function of hematopoiesis-stimulating factor receptors on the GPI− and GPI+ hematopoietic stem cells of patients with paroxysmal nocturnal hemoglobinuria/aplastic anemia syndrome

    PubMed Central

    FU, RONG; DING, SHAO-XUE; LIU, YI; LI, LI-JUAN; LIU, HUI; WANG, HONG-LEI; ZHANG, TIAN; SHAO, ZONG-HONG

    2016-01-01

    Paroxysmal nocturnal hemoglobinuria/aplastic anemia (PNH/AA) syndrome presents a markedly increased population of cells deficient in glycophosphatidylinositol (GPI− cells) and signs of bone marrow failure, which requires treatment with hematopoiesis-stimulating factors, such as granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). However, little is known about the effects of these stimulating factors on GPI− cells. In order to explore the effects of stimulating factors in PNH/AA, G-CSF receptor (CD114) and SCF receptor (CD117) expression levels on GPI+ and GPI− hematopoietic stem cells (HSCs) were measured by flow cytometry (FCM). The mean fluorescence intensity (MFI) values of signal transducer and activator of transcription 5 (STAT5) and phosphorylated (P)-STAT5 were measured in GPI+ and GPI− HSCs by FCM following stimulation with G-CSF or SCF in vitro. The expression levels of CD114 and CD117 on GPI− HSCs were significantly lower (P<0.01) than those on GPI+ HSCs in PNH/AA patients and normal controls. The MFI values of STAT5 in the GPI− and GPI+ HSCs of PNH/AA patients and normal controls were not significantly different. However, the MFI values of P-STAT5 in the GPI− HSCs of PNH/AA patients were significantly lower than those in the GPI+ HSCs of PNH/AA patients and normal controls prior to and following stimulation with G-CSF or SCF (P<0.01). The GPI− HSCs of PNH/AA patients responded poorly to stimulation by hematopoiesis-stimulating factors, which indicates that these factors can be used safely in patients with PNH/AA. PMID:27168787

  1. Preferential expression of human Fc gamma RIIIPMN (CD16) in paroxysmal nocturnal hemoglobinuria. Discordant expression of glycosyl phosphatidylinositol-linked proteins.

    PubMed Central

    Edberg, J C; Salmon, J E; Whitlow, M; Kimberly, R P

    1991-01-01

    The isoform of Fc gamma RIII (CD16) expressed on PMN has a GPI membrane anchor, and in paroxysmal nocturnal hemoglobinuria (PNH) there is a deficiency in Fc gamma RIII expression on PMN. Contrary to expectation, however, CD16 expression is preserved (albeit at reduced levels) in all affected PNH PMN that completely lack the GPI-anchored proteins DAF (CD55) and CD59. Fc gamma RIII negative PMN are not observed in any of the six PNH patients examined in this study. Analysis of the molecular weight of both glycosylated and deglycosylated Fc gamma RIII from PMN with reduced Fc gamma RIII expression indicates no variations in size relative to normal donor Fc gamma RIIIPMN. Indeed, the Fc gamma RIII expressed at intermediate levels is phosphatidylinositol-specific phospholipase C (PI-PLC)-sensitive. Thus, there is no evidence suggestive of expression of a transmembrane isoform and all data indicate that Fc gamma RIIIPMN on affected cells in PNH is a GPI-linked isoform. With Fc gamma RIIIPMN expression preserved at reduced levels on affected cells in PNH, PMN from PNH patients retain the capacity to internalize the Fc gamma RIIIPMN-specific probe E-ConA (at reduced levels) as well as IgG-opsonized erythrocytes. Reduced expression of GPI-anchored molecules on PNH PMN is not restricted to Fc gamma RIIIPMN since intermediate levels of CD59 were observed in the PNH PMN that were decay-accelerating factor (DAF)-negative and Fc gamma RIIIPMN intermediate. In addition, discordant expression of GPI-linked molecules in individual cells is not restricted to PMN since DAF+/CD14- monocytes were observed in one PNH patient. These data suggest that, when analyzed on an individual cell level, the GPI anchor defect in PNH is not absolute and must involve either a hierarchy of access of different protein molecules to available GPI anchors, distinct anchor biochemistries for the different proteins, or differential regulation of protein-anchor assembly. Images PMID:1702101

  2. Spaceborne receivers: Basic principles

    NASA Technical Reports Server (NTRS)

    Stacey, J. M.

    1984-01-01

    The underlying principles of operation of microwave receivers for space observations of planetary surfaces were examined. The design philosophy of the receiver as it is applied to operate functionally as an efficient receiving system, the principle of operation of the key components of the receiver, and the important differences among receiver types are explained. The operating performance and the sensitivity expectations for both the modulated and total power receiver configurations are outlined. The expressions are derived from first principles and are developed through the important intermediate stages to form practicle and easily applied equations. The transfer of thermodynamic energy from point to point within the receiver is illustrated. The language of microwave receivers is applied statistics.

  3. Solar heat receiver

    DOEpatents

    Hunt, A.J.; Hansen, L.J.; Evans, D.B.

    1982-09-29

    A receiver is described for converting solar energy to heat a gas to temperatures from 700 to 900/sup 0/C. The receiver is formed to minimize impingement of radiation on the walls and to provide maximum heating at and near the entry of the gas exit. Also, the receiver is formed to provide controlled movement of the gas to be heated to minimize wall temperatures. The receiver is designed for use with gas containing fine heat absorbing particles, such as carbon particles.

  4. Drugs that inhibit complement.

    PubMed

    Schrezenmeier, Hubert; Höchsmann, Britta

    2012-02-01

    The complement system is an important part of the innate immune system. Complement plays a crucial role in the pathophysiology of many disorders. Despite the pivotal role of the complement system, an approved targeted inhibitor of a complement factor became available only recently. Eculizumab is a humanized monoclonal antibody that inhibits complement factor C5. It is a targeted, disease modifying, treatment of paroxysmal nocturnal hemoglobinuria (PNH). It was approved be the US FDA and the European Commission in 2007. In this review we will update the experience with eculizumab in PNH and discuss potential use of eculizumab in other disorders (e.g. cold agglutinin disease; atypical HUS) and new approaches to complement inhibition with drugs other than eculizumab. PMID:22169380

  5. Optical superheterodyne receiver.

    NASA Technical Reports Server (NTRS)

    Duval, K.; Lang, K.; Lucy, R. F.; Peters, C. J.

    1967-01-01

    Optical communication experiments to compare coherent and noncoherent optical detection fading characteristics in different weather conditions, using laser transmitter and optical superheterodyne receiver

  6. Hybrid receiver study

    NASA Technical Reports Server (NTRS)

    Stone, M. S.; Mcadam, P. L.; Saunders, O. W.

    1977-01-01

    The results are presented of a 4 month study to design a hybrid analog/digital receiver for outer planet mission probe communication links. The scope of this study includes functional design of the receiver; comparisons between analog and digital processing; hardware tradeoffs for key components including frequency generators, A/D converters, and digital processors; development and simulation of the processing algorithms for acquisition, tracking, and demodulation; and detailed design of the receiver in order to determine its size, weight, power, reliability, and radiation hardness. In addition, an evaluation was made of the receiver's capabilities to perform accurate measurement of signal strength and frequency for radio science missions.

  7. Data-fusion receiver

    DOEpatents

    Gabelmann, Jeffrey M.; Kattner, J. Stephen; Houston, Robert A.

    2006-12-19

    This invention is an ultra-low frequency electromagnetic telemetry receiver which fuses multiple input receive sources to synthesize a decodable message packet from a noise corrupted telemetry message string. Each block of telemetry data to be sent to the surface receiver from a borehole tool is digitally encoded into a data packet prior to transmission. The data packet is modulated onto the ULF EM carrier wave and transmitted from the borehole to the surface and then are simultaneously detected by multiple receive sensors disbursed within the rig environment. The receive sensors include, but are not limited to, electric field and magnetic field sensors. The spacing of the surface receive elements is such that noise generators are unequally coupled to each receive element due to proximity and/or noise generator type (i.e. electric or magnetic field generators). The receiver utilizes a suite of decision metrics to reconstruct the original, non noise-corrupted data packet from the observation matrix via the estimation of individual data frames. The receiver will continue this estimation process until: 1) the message validates, or 2) a preset "confidence threshold" is reached whereby frames within the observation matrix are no longer "trusted".

  8. Right to Receive.

    ERIC Educational Resources Information Center

    Oborn, Richard

    The concept of a United States citizen's right to receive information is acquiring increased judicial recognition. This report traces the evolution of that right from its philosophical basis in the United States Consitution, through its interpretation by the Supreme Court, up to the current concern that the public receive certain economic…

  9. CALUTRON RECEIVER STRUCTURE

    DOEpatents

    Roush, J.L.

    1959-09-01

    A receiver is described for collecting isotopes in a calutron The receiver has several compartments, formed by a sertes of parallel metal plates and an open front. Each plate has flanges which space it from the other plates and a flexible extension pressing against a common supporting red to maintain the plate in assembled relation when all but the last rod is removed. The plates may be removed individualy from the front of the receiver, cleaned ard replaced without disturbing the alignment of the other plates.

  10. Ultrasonic pulser-receiver

    SciTech Connect

    Taylor, Steven C.

    2006-09-12

    Ultrasonic pulser-receiver circuitry, for use with an ultrasonic transducer, the circuitry comprising a circuit board; ultrasonic pulser circuitry supported by the circuit board and configured to be coupled to an ultrasonic transducer and to cause the ultrasonic transducer to emit an ultrasonic output pulse; receiver circuitry supported by the circuit board, coupled to the pulser circuitry, including protection circuitry configured to protect against the ultrasonic pulse and including amplifier circuitry configured to amplify an echo, received back by the transducer, of the output pulse; and a connector configured to couple the ultrasonic transducer directly to the circuit board, to the pulser circuitry and receiver circuitry, wherein impedance mismatches that would result if the transducer was coupled to the circuit board via a cable can be avoided.

  11. Ceramic Solar Receiver

    NASA Technical Reports Server (NTRS)

    Robertson, C., Jr.

    1984-01-01

    Solar receiver uses ceramic honeycomb matrix to absorb heat from Sun and transfer it to working fluid at temperatures of 1,095 degrees and 1,650 degrees C. Drives gas turbine engine or provides heat for industrial processes.

  12. Solar energy receiver

    DOEpatents

    Schwartz, Jacob

    1978-01-01

    An improved long-life design for solar energy receivers provides for greatly reduced thermally induced stress and permits the utilization of less expensive heat exchanger materials while maintaining receiver efficiencies in excess of 85% without undue expenditure of energy to circulate the working fluid. In one embodiment, the flow index for the receiver is first set as close as practical to a value such that the Graetz number yields the optimal heat transfer coefficient per unit of pumping energy, in this case, 6. The convective index for the receiver is then set as closely as practical to two times the flow index so as to obtain optimal efficiency per unit mass of material.

  13. Receiver Gain Modulation Circuit

    NASA Technical Reports Server (NTRS)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  14. Highly directional acoustic receivers.

    PubMed

    Cray, Benjamin A; Evora, Victor M; Nuttall, Albert H

    2003-03-01

    The theoretical directivity of a single combined acoustic receiver, a device that can measure many quantities of an acoustic field at a collocated point, is presented here. The formulation is developed using a Taylor series expansion of acoustic pressure about the origin of a Cartesian coordinate system. For example, the quantities measured by a second-order combined receiver, denoted a dyadic sensor, are acoustic pressure, the three orthogonal components of acoustic particle velocity, and the nine spatial gradients of the velocity vector. The power series expansion, which can be of any order, is cast into an expression that defines the directivity of a single receiving element. It is shown that a single highly directional dyadic sensor can have a directivity index of up to 9.5 dB. However, there is a price to pay with highly directive sensors; these sensors can be significantly more sensitive to nonacoustic noise sources. PMID:12656387

  15. Central solar energy receiver

    DOEpatents

    Drost, M. Kevin

    1983-01-01

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  16. Submillimeter wave heterodyne receiver

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutam (Inventor); Manohara, Harish (Inventor); Siegel, Peter H. (Inventor); Ward, John (Inventor)

    2011-01-01

    In an embodiment, a submillimeter wave heterodyne receiver includes a finline ortho-mode transducer comprising thin tapered metallic fins deposited on a thin dielectric substrate to separate a vertically polarized electromagnetic mode from a horizontally polarized electromagnetic mode. Other embodiments are described and claimed.

  17. Olympus beacon receiver

    NASA Technical Reports Server (NTRS)

    Ostergaard, Jens

    1988-01-01

    A medium-size Beacon Receiving System for reception and processing of the B1 (20 GHz) and B2 (30 GHz) beacons from Olympus has been developed. Integration of B1 and B2 receiving equipment into one system using one antenna and a common computer for control and data processing provides the advantages of a compact configuration and synchronization of the two receiver chains. Range for co-polar signal attenuation meaurement is about 30 dB for both beacons, increasing to 40 dB for B2 if the receivers are synchronized to B1. The accuracy is better than 0.5 dB. Cross-polarization discriminations of the order of 10 to 30 dB may be determined with an accuracy of 1 to 2 dB. A number of radiometers for complementary measurements of atmospheric attenuation of 13 to 30 GHz has also been constructed. A small multi-frequency system for operation around 22 GHz and 31 GHz is presently under development.

  18. Simplified OMEGA receivers

    NASA Technical Reports Server (NTRS)

    Burhans, R. W.

    1974-01-01

    The details are presented of methods for providing OMEGA navigational information including the receiver problem at the antenna and informational display and housekeeping systems based on some 4 bit data processing concepts. Topics discussed include the problem of limiters, zero crossing detectors, signal envelopes, internal timing circuits, phase counters, lane position displays, signal integrators, and software mapping problems.

  19. A digital beacon receiver

    NASA Technical Reports Server (NTRS)

    Ransome, Peter D.

    1988-01-01

    A digital satellite beacon receiver is described which provides measurement information down to a carrier/noise density ratio approximately 15 dB below that required by a conventional (phase locked loop) design. When the beacon signal fades, accuracy degrades gracefully, and is restored immediately (without hysteresis) on signal recovery, even if the signal has faded into the noise. Benefits of the digital processing approach used include the minimization of operator adjustments, stability of the phase measuring circuits with time, repeatability between units, and compatibility with equipment not specifically designed for propagation measuring. The receiver has been developed for the European Olympus satellite which has continuous wave (CW) beacons at 12.5 and 29.7 GHz, and a switched polarization beacon at 19.8 GHz approximately, but the system can be reconfigured for CW and polarization-switched beacons at other frequencies.

  20. Galileo probe relay receiver

    NASA Technical Reports Server (NTRS)

    Prouty, D. A.; Von Der Embse, U. A.

    1982-01-01

    For the Jovian mission, the data link from the Galileo probe to the orbiter uses suppressed-carrier Manchester encoded BPSK modulation and is protected with R = 1/2, K = 7 convolutional coding. The receiver closes the link by acquiring, tracking, and demodulating the data. It has to operate in a highly stressed environment with severe frequency offset, frequency rate, wind gust, and antenna spin conditions. Salient features are described and breadboard test data presented.

  1. Multichannel homodyne receiver

    DOEpatents

    Landt, Jeremy A.

    1982-01-01

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  2. Multichannel homodyne receiver

    DOEpatents

    Landt, J.A.

    1981-01-19

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals is described. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  3. LANL receiver system development

    SciTech Connect

    Laubscher, B.; Cooke, B.; Cafferty, M.; Olivas, N.

    1997-08-01

    The CALIOPE receiver system development at LANL is the story of two technologies. The first of these technologies consists of off-the-shelf mercury-cadmium-telluride (MCT) detectors and amplifiers. The vendor for this system is Kolmar Technologies. This system was fielded in the Tan Trailer I (TTI) in 1995 and will be referred to in this paper as GEN I. The second system consists of a MCT detector procured from Santa Barbara Research Center (SBRC) and an amplifier designed and built by LANL. This system was fielded in the Tan Trailer II (TTII) system at the NTS tests in 1996 and will be referred to as GEN II. The LANL CALIOPE experimental plan for 1996 was to improve the lidar system by progressing to a higher rep rate laser to perform many shots in a much shorter period of time. In keeping with this plan, the receiver team set a goal of developing a detector system that was background limited for the projected 100 nanosecond (ns) laser pulse. A set of detailed simulations of the DIAL lidar experiment was performed. From these runs, parameters such as optimal detector size, field of view of the receiver system, nominal laser return power, etc. were extracted. With this information, detector physics and amplifier electronic models were developed to obtain the required specifications for each of these components. These derived specs indicated that a substantial improvement over commercially available, off-the-shelf, amplifier and detector technologies would be needed to obtain the goals. To determine if the original GEN I detector was usable, the authors performed tests on a 100 micron square detector at cryogenic temperatures. The results of this test and others convinced them that an advanced detector was required. Eventually, a suitable detector was identified and a number of these single element detectors were procured from SBRC. These single element detectors were witness for the detector arrays built for another DOE project.

  4. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1994-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  5. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1996-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  6. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1996-06-04

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, {+-}UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 21 figs.

  7. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1994-09-06

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, [+-] UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 16 figs.

  8. Weather Data Receiver

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Northern Video Graphics, Inc. developed a low-cost satellite receiving system for users such as independent meteorologists, agribusiness firms, small airports or flying clubs, marine vessels and small TV stations. Called Video Fax, it is designed for use with certain satellites; the GOES (Geostationary Operational Environmental Satellite) spacecraft operated by the National Oceanic and Atmospheric Administration, the European Space Agency's Meteosat and Japan's Geostationary Meteorological Satellite. By dictum of the World Meteorological Organization, signals from satellites are available to anyone without cost so the Video Fax user can acquire signals directly from the satellite and cut out the middle man, enabling savings. Unit sells for about one-fifth the cost of the equipment used by TV stations. It consists of a two-meter antenna; a receiver; a microprocessor-controlled display computer; and a video monitor. Computer stores data from the satellites and converts it to an image which is displayed on the monitor. Weather map can be preserved as signal data on tape, or it can be stored in a video cassette as a permanent image.

  9. Digital Receiver Phase Meter

    NASA Technical Reports Server (NTRS)

    Marcin, Martin; Abramovici, Alexander

    2008-01-01

    The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density <5 microcycle/(Hz)1/2 and to be capable of determining the power spectral density of the phase difference over the frequency range from 1 mHz to 1 Hz. Such a phase meter could also be used on Earth to perform similar measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

  10. Solar thermal energy receiver

    NASA Technical Reports Server (NTRS)

    Baker, Karl W. (Inventor); Dustin, Miles O. (Inventor)

    1992-01-01

    A plurality of heat pipes in a shell receive concentrated solar energy and transfer the energy to a heat activated system. To provide for even distribution of the energy despite uneven impingement of solar energy on the heat pipes, absence of solar energy at times, or failure of one or more of the heat pipes, energy storage means are disposed on the heat pipes which extend through a heat pipe thermal coupling means into the heat activated device. To enhance energy transfer to the heat activated device, the heat pipe coupling cavity means may be provided with extensions into the device. For use with a Stirling engine having passages for working gas, heat transfer members may be positioned to contact the gas and the heat pipes. The shell may be divided into sections by transverse walls. To prevent cavity working fluid from collecting in the extensions, a porous body is positioned in the cavity.

  11. Advanced space solar dynamic receivers

    NASA Technical Reports Server (NTRS)

    Strumpf, Hal J.; Coombs, Murray G.; Lacy, Dovie E.

    1988-01-01

    A study has been conducted to generate and evaluate advanced solar heat receiver concepts suitable for orbital application with Brayton and Stirling engine cycles in the 7-kW size range. The generated receiver designs have thermal storage capability (to enable power production during the substantial eclipse period which accompanies typical orbits) and are lighter and smaller than state-of-the-art systems, such as the Brayton solar receiver being designed and developed by AiResearch for the NASA Space Station. Two receiver concepts have been developed in detail: a packed bed receiver and a heat pipe receiver. The packed bed receiver is appropriate for a Brayton engine; the heat pipe receiver is applicable for either a Brayton or Stirling engine. The thermal storage for both concepts is provided by the melting and freezing of a salt. Both receiver concepts offer substantial improvements in size and weight compared to baseline receivers.

  12. Anchorage Receives Record Snowfall

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The forecast called for flurries, but the snow accumulated on the ground in Anchorage, Alaska, at the rate of 2 inches per hour (5 cm per hour) for much of Saturday, March 16, 2002. By the time the winter storm passed on Sunday afternoon, Anchorage had received 28.6 inches (72.6 cm) of snow, surpassing by far the previous record of 15.6 inches (39.6 cm) set on December 29, 1955. Flights were canceled and schools were closed as a result of the storm. This true-color image of Alaska was acquired by the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), flying aboard the OrbView-2 satellite, on March 18. It appears another large, low-pressure system is heading toward the Anchorage region, which could bring substantially more snowfall. The low-pressure system can be identified by the characteristic spiral pattern of clouds located off Alaska's southwestern coast in this scene.

  13. ADMX Receiver and Analysis

    NASA Astrophysics Data System (ADS)

    Malagon, Ana; ADMX Collaboration

    2016-03-01

    ADMX looks for the excess radiation deposited into a cavity from the conversion of a dark matter axion into a microwave photon. The sensitivity of the experiment increases by reducing the background thermal noise and minimizing the electronic noise of the readout system. The axion masses that the experiment can detect are determined by the resonant frequency of the cavity mode of interest, which is tuned using a two rod configuration. One can also increase the search rate by measuring the output from two cavity modes at once, which requires two separate readout schemes. I will discuss the ADMX dual-channel receiver which has been upgraded to have near quantum-limited sensitivity on both channels, and describe how the correct modes are verified, using simulations, in the presence of dense electromagnetic structure. I conclude by describing upgrades to the ADMX analysis which allow for real-time exclusion limits. Supported by DOE Grants DE-FG02-97ER41029, DE-FG02-96ER40956, DE- AC52-07NA27344, DE-AC03-76SF00098, and the Livermore LDRD program.

  14. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2007-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  15. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2006-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  16. High temperature solar thermal receiver

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A design concept for a high temperature solar thermal receiver to operate at 3 atmospheres pressure and 2500 F outlet was developed. The performance and complexity of windowed matrix, tube-header, and extended surface receivers were evaluated. The windowed matrix receiver proved to offer substantial cost and performance benefits. An efficient and cost effective hardware design was evaluated for a receiver which can be readily interfaced to fuel and chemical processes or to heat engines for power generation.

  17. High-temperature ceramic receivers

    SciTech Connect

    Jarvinen, P. O.

    1980-01-01

    An advanced ceramic dome cavity receiver is discussed which heats pressurized gas to temperatures above 1800/sup 0/F (1000/sup 0/C) for use in solar Brayton power systems of the dispersed receiver/dish or central receiver type. Optical, heat transfer, structural, and ceramic material design aspects of the receiver are reported and the development and experimental demonstration of a high-temperature seal between the pressurized gas and the high-temperature silicon carbide dome material is described.

  18. Receiving signals of any polarization

    NASA Technical Reports Server (NTRS)

    Ohlson, J. E.; Seidel, B. L.; Stelzried, C. H.

    1981-01-01

    Two-channel detection accomodates linear, circular, and elliptical polarization in one receiving unit. Receiver employs orthomode transducer which breaks any type signal into one left and one right circular component. These are processed in separate receiver channels with equal time-delay, and then recombined for data extraction. System eliminates losses due to polarization mismatch.

  19. Reflux solar receiver design considerations

    NASA Astrophysics Data System (ADS)

    Diver, R. B.

    Reflux heat-pipe and pool-boiler receivers are being developed to improve upon the performance and life of directly-illuminated tube receiver technology used in previous successful demonstrations of dish-Stirling systems. The design of a reflux receiver involves engineering tradeoffs. In this paper, on-sun performance measurements of the Sandia pool-boiler receiver are compared with results from the reflux receiver thermal analysis model, AEETES. Flux and performance implications of various design options are analyzed and discussed.

  20. Advanced solar thermal receiver technology

    NASA Technical Reports Server (NTRS)

    Kudirka, A. A.; Leibowitz, L. P.

    1980-01-01

    Development of advanced receiver technology for solar thermal receivers designed for electric power generation or for industrial applications, such as fuels and chemical production or industrial process heat, is described. The development of this technology is focused on receivers that operate from 1000 F to 3000 F and above. Development strategy is mapped in terms of application requirements, and the related system and technical requirements. Receiver performance requirements and current development efforts are covered for five classes of receiver applications: high temperature, advanced Brayton, Stirling, and Rankine cycle engines, and fuels and chemicals.

  1. Genetics Home Reference: paroxysmal nocturnal hemoglobinuria

    MedlinePlus

    ... at increased risk of developing cancer in blood-forming cells (leukemia). In some cases, people who have ... mutations of the PIGA gene occur in blood-forming cells called hematopoietic stem cells, which are found ...

  2. Bragg-cell receiver study

    NASA Technical Reports Server (NTRS)

    Wilson, Lonnie A.

    1987-01-01

    Bragg-cell receivers are employed in specialized Electronic Warfare (EW) applications for the measurement of frequency. Bragg-cell receiver characteristics are fully characterized for simple RF emitter signals. This receiver is early in its development cycle when compared to the IFM receiver. Functional mathematical models are derived and presented in this report for the Bragg-cell receiver. Theoretical analysis is presented and digital computer signal processing results are presented for the Bragg-cell receiver. Probability density function analysis are performed for output frequency. Probability density function distributions are observed to depart from assumed distributions for wideband and complex RF signals. This analysis is significant for high resolution and fine grain EW Bragg-cell receiver systems.

  3. RFI receiver. [deep space network

    NASA Technical Reports Server (NTRS)

    Lay, R.

    1980-01-01

    An S-band radio frequency interference (RFI) receiver to analyze and identify sources of RFI problems in the Deep Space Network DSN tracking stations is described. The RFI receiver is a constant gain, double conversion, open loop receiver with dual sine/cosine channel outputs, providing a total of 20 MHZ monitoring capability. This receiver is computer controlled using a MODCOMP II miniprocessor. The RFI receiver has been designed to operate at a 150 Kelvin system noise temperature accomplished by cascading two low noise field effect transistor (FET) amplifiers for the receiver front-end. The first stage low noise FET amplifier is mounted at the feed horn to minimize any cable losses to achieve a lower system noise temperature. The receiver is tunable over the frequency range of 2150 to 2450 MHz in both sine/cosine output channels with a resolution of 100 kHz.

  4. Performance testing of lidar receivers

    NASA Technical Reports Server (NTRS)

    Shams, M. Y.

    1986-01-01

    In addition to the considerations about the different types of noise sources, dynamic range, and linearity of a lidar receiver, one requires information about the pulse shape retaining capabilities of the receiver. For this purpose, relatively precise information about the height resolution as well as the recovery time of the receiver, due both to large transients and to fast changes in the received signal, is required. As more and more analog receivers using fast analog to digital converters and transient recorders will be used in the future lidar systems, methods to test these devices are essential. The method proposed for this purpose is shown. Tests were carried out using LCW-10, LT-20, and FTVR-2 as optical parts of the optical pulse generator circuits. A commercial optical receiver, LNOR, and a transient recorder, VK 220-4, were parts of the receiver system.

  5. Immigration: perspectives from receiving countries.

    PubMed

    Weiner, M

    1990-01-01

    The author examines the issue of international migration from the standpoint of receiving countries. He attempts "to understand how and why migrant-receiving countries respond as they do, and to suggest some of the new issues in international migration that arise in a world in which the supply of would-be migrants and refugees is now greater than receiving countries are willing to accept." PMID:12283227

  6. UWB delay and multiply receiver

    DOEpatents

    Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

    2013-09-10

    An ultra-wideband (UWB) delay and multiply receiver is formed of a receive antenna; a variable gain attenuator connected to the receive antenna; a signal splitter connected to the variable gain attenuator; a multiplier having one input connected to an undelayed signal from the signal splitter and another input connected to a delayed signal from the signal splitter, the delay between the splitter signals being equal to the spacing between pulses from a transmitter whose pulses are being received by the receive antenna; a peak detection circuit connected to the output of the multiplier and connected to the variable gain attenuator to control the variable gain attenuator to maintain a constant amplitude output from the multiplier; and a digital output circuit connected to the output of the multiplier.

  7. Customizable Digital Receivers for Radar

    NASA Technical Reports Server (NTRS)

    Moller, Delwyn; Heavey, Brandon; Sadowy, Gregory

    2008-01-01

    Compact, highly customizable digital receivers are being developed for the system described in 'Radar Interferometer for Topographic Mapping of Glaciers and Ice Sheets' (NPO-43962), NASA Tech Briefs, Vol. 31, No. 7 (August 2007), page 72. The receivers are required to operate in unison, sampling radar returns received by the antenna elements in a digital beam-forming (DBF) mode. The design of these receivers could also be adapted to commercial radar systems. At the time of reporting the information for this article, there were no commercially available digital receivers capable of satisfying all of the operational requirements and compact enough to be mounted directly on the antenna elements. A provided figure depicts the overall system of which the digital receivers are parts. Each digital receiver includes an analog-to-digital converter (ADC), a demultiplexer (DMUX), and a field-programmable gate array (FPGA). The ADC effects 10-bit band-pass sampling of input signals having frequencies up to 3.5 GHz. The input samples are demultiplexed at a user-selectable rate of 1:2 or 1:4, then buffered in part of the FPGA that functions as a first-in/first-out (FIFO) memory. Another part of the FPGA serves as a controller for the ADC, DMUX, and FIFO memory and as an interface between (1) the rest of the receiver and (2) a front-panel data port (FPDP) bus, which is an industry-standard parallel data bus that has a high data-rate capability and multichannel configuration suitable for DBF. Still other parts of the FPGA in each receiver perform signal-processing functions. The digital receivers can be configured to operate in a stand-alone mode, or in a multichannel mode as needed for DBF. The customizability of the receiver makes it applicable to a broad range of system architectures. The capability for operation of receivers in either a stand-alone or a DBF mode enables the use of the receivers in an unprecedentedly wide variety of radar systems.

  8. Coe Receives 2007 Gilbert Award

    NASA Astrophysics Data System (ADS)

    Bogue, Scott W.; Coe, Robert S.

    2008-05-01

    Robert S. Coe received the 2007 William Gilbert Award at the 2007 AGU Fall Meeting in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  9. Streak camera receiver definition study

    NASA Technical Reports Server (NTRS)

    Johnson, C. B.; Hunkler, L. T., Sr.; Letzring, S. A.; Jaanimagi, P.

    1990-01-01

    Detailed streak camera definition studies were made as a first step toward full flight qualification of a dual channel picosecond resolution streak camera receiver for the Geoscience Laser Altimeter and Ranging System (GLRS). The streak camera receiver requirements are discussed as they pertain specifically to the GLRS system, and estimates of the characteristics of the streak camera are given, based upon existing and near-term technological capabilities. Important problem areas are highlighted, and possible corresponding solutions are discussed.

  10. Next generation digital GPS receiver

    NASA Astrophysics Data System (ADS)

    Frank, G. B.; Yakos, Michael D.

    1990-07-01

    The architecture and technology features of the next-generation (NGR) digital GPS receiver manufactured by Collins are described. The project's objective was to develop an advanced GPS receiver chipset with high antijam capabilities. The program, initiated in 1985, has provided the technology for miniature receiver products for both unmanned and manned vehicle applications. A two-channel version of the receiver is currently in full-scale development for tactical missile applications. A five-channel version is being tested and evaluated as a drop-in replacement for RCVR-3A, the US Department of Defense standard high dynamic receiver. The NGR design started with the digital signal processing architecture developed for the Defense Advanced Research Project Agency (DARPA) hand-held GPS receiver. Enhancements were made to improve the antijam and signal acquisition performance. Producible, qualifiable and cost-effective silicon monolithic microwave integrated circuits and semicustom digital technologies were used to develop the core GPS chipset. A system design approach was established to permit reuse of mature and validated GPS software.

  11. Solar dynamic heat receiver technology

    NASA Technical Reports Server (NTRS)

    Sedgwick, Leigh M.

    1991-01-01

    A full-size, solar dynamic heat receiver was designed to meet the requirements specified for electrical power modules on the U.S. Space Station, Freedom. The heat receiver supplies thermal energy to power a heat engine in a closed Brayton cycle using a mixture of helium-xenon gas as the working fluid. The electrical power output of the engine, 25 kW, requires a 100 kW thermal input throughout a 90 minute orbit, including when the spacecraft is eclipsed for up to 36 minutes from the sun. The heat receiver employs an integral thermal energy storage system utilizing the latent heat available through the phase change of a high-temperature salt mixture. A near eutectic mixture of lithium fluoride and calcium difluoride is used as the phase change material. The salt is contained within a felt metal matrix which enhances heat transfer and controls the salt void distribution during solidification. Fabrication of the receiver is complete and it was delivered to NASA for verification testing in a simulated low-Earth-orbit environment. This document reviews the receiver design and describes its fabrication history. The major elements required to operate the receiver during testing are also described.

  12. PPM Receiver Implemented in Software

    NASA Technical Reports Server (NTRS)

    Gray, Andrew; Kang, Edward; Lay, Norman; Vilnrotter, Victor; Srinivasan, Meera; Lee, Clement

    2010-01-01

    A computer program has been written as a tool for developing optical pulse-position- modulation (PPM) receivers in which photodetector outputs are fed to analog-to-digital converters (ADCs) and all subsequent signal processing is performed digitally. The program can be used, for example, to simulate an all-digital version of the PPM receiver described in Parallel Processing of Broad-Band PPM Signals (NPO-40711), which appears elsewhere in this issue of NASA Tech Briefs. The program can also be translated into a design for digital PPM receiver hardware. The most notable innovation embodied in the software and the underlying PPM-reception concept is a digital processing subsystem that performs synchronization of PPM time slots, even though the digital processing is, itself, asynchronous in the sense that no attempt is made to synchronize it with the incoming optical signal a priori and there is no feedback to analog signal processing subsystems or ADCs. Functions performed by the software receiver include time-slot synchronization, symbol synchronization, coding preprocessing, and diagnostic functions. The program is written in the MATLAB and Simulink software system. The software receiver is highly parameterized and, hence, programmable: for example, slot- and symbol-synchronization filters have programmable bandwidths.

  13. Receiver-exciter controller design

    NASA Astrophysics Data System (ADS)

    Jansma, P. A.

    1982-06-01

    A description of the general design of both the block 3 and block 4 receiver-exciter controllers for the Deep Space Network (DSN) Mark IV-A System is presented along with the design approach. The controllers are designed to enable the receiver-exciter subsystem (RCV) to be configured, calibrated, initialized and operated from a central location via high level instructions. The RECs are designed to be operated under the control of the DMC subsystem. The instructions are in the form of standard subsystem blocks (SSBs) received via the local area network (LAN). The centralized control provided by RECs and other DSCC controllers in Mark IV-A is intended to reduce DSN operations costs from the Mark III era.

  14. Receiver-exciter controller design

    NASA Technical Reports Server (NTRS)

    Jansma, P. A.

    1982-01-01

    A description of the general design of both the block 3 and block 4 receiver-exciter controllers for the Deep Space Network (DSN) Mark IV-A System is presented along with the design approach. The controllers are designed to enable the receiver-exciter subsystem (RCV) to be configured, calibrated, initialized and operated from a central location via high level instructions. The RECs are designed to be operated under the control of the DMC subsystem. The instructions are in the form of standard subsystem blocks (SSBs) received via the local area network (LAN). The centralized control provided by RECs and other DSCC controllers in Mark IV-A is intended to reduce DSN operations costs from the Mark III era.

  15. UWB communication receiver feedback loop

    DOEpatents

    Spiridon, Alex; Benzel, Dave; Dowla, Farid U.; Nekoogar, Faranak; Rosenbury, Erwin T.

    2007-12-04

    A novel technique and structure that maximizes the extraction of information from reference pulses for UWB-TR receivers is introduced. The scheme efficiently processes an incoming signal to suppress different types of UWB as well as non-UWB interference prior to signal detection. Such a method and system adds a feedback loop mechanism to enhance the signal-to-noise ratio of reference pulses in a conventional TR receiver. Moreover, sampling the second order statistical function such as, for example, the autocorrelation function (ACF) of the received signal and matching it to the ACF samples of the original pulses for each transmitted bit provides a more robust UWB communications method and system in the presence of channel distortions.

  16. Frequency synthesizers for telemetry receivers

    NASA Astrophysics Data System (ADS)

    Stirling, Ronald C.

    1990-07-01

    The design of a frequency synthesizer is presented for telemetry receivers. The synthesizer contains two phase-locked loops, each with a programmable frequency counter, and incorporates fractional frequency synthesis but does not use a phase accumulator. The selected receiver design has a variable reference loop operating as a part of the output loop. Within the synthesizer, a single VTO generates the output frequency that is voltage-tunable from 375-656 MHz. The single-sideband phase noise is measured with an HP 8566B spectrum analyzer, and the receiver's bit error rate (BER) is measured with a carrier frequency of 250 MHz, synthesized LO at 410 MHz, and the conditions of BPSK, NRZ-L, and 2.3 kHz bit rate. The phase noise measurement limits and the BER performance data are presented in tabular form.

  17. Central solar-energy receiver

    DOEpatents

    Not Available

    1981-10-27

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan is described. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  18. Digital Receiver for Microwave Radiometry

    NASA Technical Reports Server (NTRS)

    Ellingson, Steven W.; Hampson, Grant A.; Johnson, Joel T.

    2005-01-01

    A receiver proposed for use in L-band microwave radiometry (for measuring soil moisture and sea salinity) would utilize digital signal processing to suppress interfering signals. Heretofore, radio frequency interference has made it necessary to limit such radiometry to a frequency band about 20 MHz wide, centered at .1,413 MHz. The suppression of interference in the proposed receiver would make it possible to expand the frequency band to a width of 100 MHz, thereby making it possible to obtain greater sensitivity and accuracy in measuring moisture and salinity

  19. Optical receivers using rough reflectors

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V. A.

    1985-01-01

    This report examines the possible use of rough, or nondiffraction-limited, reflectors for collecting optical signals. It is shown that in the absence of background radiation, the reflector's surface quality has little effect on the performance of a properly designed receiver, but that the presence of even small amounts of background radiation can lead to severe performance degradation. Techniques are suggested for improving receiver performance in high-background environments, and bounds and approximations to the exact error-probability expressions are derived.

  20. The GBT 4mm Receiver

    NASA Astrophysics Data System (ADS)

    Frayer, David T.; White, S.; Watts, G.; Stennes, M.; Maddalena, R. J.; Simon, R.; Pospieszalski, M.; Bryerton, E.

    2013-01-01

    The new 4mm receiver (67--93 GHz) for the Robert C. Byrd Green Bank Telescope (GBT) was built to take advantage of the improved surface accuracy of the dish. The low frequency end of the 3mm atmospheric window is not available with ALMA (<84 GHz), and the sensitivity of the GBT is better than any other facility within this band. We discuss the design and performance of this new receiver for the GBT, and highlight the science opportunities available with the instrument. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

  1. Advances in SIS receiver technology

    NASA Technical Reports Server (NTRS)

    Frerking, M. A.

    1988-01-01

    Significant advances in SIS receiver technology since the last Asilomar meeting include: superconductor materials, integrated inductive tuning elements, and planar mounting structures. The effect of these advances is to push the upper frequency operating limit from about 600 to 1500 GHz, and to enhance the feasibility of focal plane arrays of heterodyne receivers. A fundamental high frequency operating limit of SIS mixers is set by the superconducting energy gap. A practical limitation for high frequency operation of SIS junctions is their parasitic capacitance and resistance. The performance of the mixer will be degraded by the Resistor-Capacitor rolloff. Several designs were reported for inductive elements integrated on the same substrate as the SIS junctions to tune out the bulk junction capacitance. Most millimeter SIS-based heterodyne receivers have used waveguide coupling structures. Technology has advanced to the state where programs that have a high probability of success can be defined to produce arrays of SIS receivers for frequencies as high as 1500 GHz.

  2. Microwave blackbodies for spaceborne receivers

    NASA Technical Reports Server (NTRS)

    Stacey, J. M.

    1985-01-01

    The properties of microwave blackbody targets are explained as they apply to the calibration of spaceborne receivers. Also described are several practicable, blackbody targets used to test and calibrate receivers in the laboratory and in the thermal vacuum chamber. Problems with the precision and the accuracy of blackbody targets, and blackbody target design concepts that overcome some of the accuracy limitations present in existing target designs, are presented. The principle of the Brewster angle blackbody target is described where the blackbody is applied as a fixed-temperature test target in the laboratory and as a variable-temperature target in the thermal vacuum chamber. The reflectivity of a Brewster angle target is measured in the laboratory. From this measurement, the emissivity of the target is calculated. Radiatively cooled thermal suspensions are discussed as the coolants of blackbody targets and waveguide terminations that function as calibration devices in spaceborne receivers. Examples are given for the design of radiatively cooled thermal suspensions. Corrugated-horn antennas used to observe the cosmic background and to provide a cold-calibration source for spaceborne receivers are described.

  3. RFID receiver apparatus and method

    DOEpatents

    Scott, Jeffrey Wayne

    2006-12-26

    An RFID backscatter interrogator for transmitting data to an RFID tag, generating a carrier for the tag, and receiving data from the tag modulated onto the carrier, the interrogator including a single grounded-coplanar wave-guide circuit board and at least one surface mount integrated circuit supported by the circuit board.

  4. Clark Receives Ocean Sciences Award

    NASA Astrophysics Data System (ADS)

    Roman, Michael R.; Clark, H. Lawrence

    2008-09-01

    H. Lawrence Clark received the 2008 Ocean Sciences Award at the 2008 Ocean Sciences Meeting, held 2-7 March 2008 in Orlando, Fla. The award is given in recognition of outstanding and long-standing service to the ocean sciences.

  5. Converting accounts receivable into cash.

    PubMed

    Folk, M D; Roest, P R

    1995-09-01

    In recent years, increasing numbers of healthcare providers have converted their accounts receivable into cash through a process called securitization. This practice has gained popularity because it provides a means to raise capital necessary to healthcare organizations. Although securitization transactions can be complex, they may provide increased financial flexibility to providers as they prepare for continuing change in the healthcare industry. PMID:10145096

  6. Femtosecond Photon-Counting Receiver

    NASA Technical Reports Server (NTRS)

    Krainak, Michael A.; Rambo, Timothy M.; Yang, Guangning; Lu, Wei; Numata, Kenji

    2016-01-01

    An optical correlation receiver is described that provides ultra-precise distance and/or time-pulse-width measurements even for weak (single photons) and short (femtosecond) optical signals. A new type of optical correlation receiver uses a fourth-order (intensity) interferometer to provide micron distance measurements even for weak (single photons) and short (femtosecond) optical signals. The optical correlator uses a low-noise-integrating detector that can resolve photon number. The correlation (range as a function of path delay) is calculated from the variance of the photon number of the difference of the optical signals on the two detectors. Our preliminary proof-of principle data (using a short-pulse diode laser transmitter) demonstrates tens of microns precision.

  7. Femtosecond Photon-Counting Receiver

    NASA Technical Reports Server (NTRS)

    Krainak, Michael A.; Rambo, Timothy M.; Yang, Guangning; Lu, Wei; Numata, Kenji

    2016-01-01

    An optical correlation receiver is described that provides ultra-precise distance and/or time/pulse-width measurements even for weak (single photons) and short (femtosecond) optical signals. A new type of optical correlation receiver uses a fourth-order (intensity) interferometer to provide micron distance measurements even for weak (single photons) and short (femtosecond) optical signals. The optical correlator uses a low-noise-integrating detector that can resolve photon number. The correlation (range as a function of path delay) is calculated from the variance of the photon number of the difference of the optical signals on the two detectors. Our preliminary proof-of principle data (using a short-pulse diode laser transmitter) demonstrates tens of microns precision.

  8. SAW correlator spread spectrum receiver

    DOEpatents

    Brocato, Robert W

    2014-04-01

    A surface acoustic wave (SAW) correlator spread-spectrum (SS) receiver is disclosed which utilizes a first demodulation stage with a chip length n and a second demodulation stage with a chip length m to decode a transmitted SS signal having a code length l=n.times.m which can be very long (e.g. up to 2000 chips or more). The first demodulation stage utilizes a pair of SAW correlators which demodulate the SS signal to generate an appropriate code sequence at an intermediate frequency which can then be fed into the second demodulation stage which can be formed from another SAW correlator, or by a digital correlator. A compound SAW correlator comprising two input transducers and a single output transducer is also disclosed which can be used to form the SAW correlator SS receiver, or for use in processing long code length signals.

  9. 30 GHz Commercial Satellite Receivers

    NASA Technical Reports Server (NTRS)

    Kerczewski, Robert J.; Ponchak, George E.; Romanofsky, Robert R.

    1989-01-01

    NASA's research and development work in satellite communications for the past 10 years has included a major technology thrust aimed at opening the Ka frequency band to commercial exploitation. This has included the development and testing of advanced system network architectures, on-board switching and processing, multibeam and phased array antennas, and satellite and ground terminal RF and digital hardware. Development work in system hardware has focused on critical components including power amplifiers, satellite IF switch matrices, low noise receivers, baseband processors, and high data rate bandwidth efficient modems. This paper describes NASA's work in developing and testing 30 GHz low noise satellite receivers for commercial space communications uplink applications. Frequencies allotted for fixed service commercial satellite communications in the Ka band are 27.5 - 30.0 GHz for uplink transmission and 17.7 - 20.2 GHz for downlink transmission. The relatively large 2.5 GHz bandwidth lends itself to wideband, high data rate digital transmission applications.

  10. Scintillation-Hardened GPS Receiver

    NASA Technical Reports Server (NTRS)

    Stephens, Donald R.

    2015-01-01

    CommLargo, Inc., has developed a scintillation-hardened Global Positioning System (GPS) receiver that improves reliability for low-orbit missions and complies with NASA's Space Telecommunications Radio System (STRS) architecture standards. A software-defined radio (SDR) implementation allows a single hardware element to function as either a conventional radio or as a GPS receiver, providing backup and redundancy for platforms such as the International Space Station (ISS) and high-value remote sensing platforms. The innovation's flexible SDR implementation reduces cost, weight, and power requirements. Scintillation hardening improves mission reliability and variability. In Phase I, CommLargo refactored an open-source GPS software package with Kalman filter-based tracking loops to improve performance during scintillation and also demonstrated improved navigation during a geomagnetic storm. In Phase II, the company generated a new field-programmable gate array (FPGA)-based GPS waveform to demonstrate on NASA's Space Communication and Navigation (SCaN) test bed.

  11. Digital-data receiver synchronization

    DOEpatents

    Smith, Stephen F.; Turner, Gary W.

    2005-08-02

    Digital-data receiver synchronization is provided with composite phase-frequency detectors, mutually cross-connected comparison feedback or both to provide robust reception of digital data signals. A single master clock can be used to provide frequency signals. Advantages can include fast lock-up time in moderately to severely noisy conditions, greater tolerance to noise and jitter when locked, and improved tolerance to clock asymmetries.

  12. Stennis group receives NESC award

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The NASA Engineering & Safety Center recently presented its Group Achievement Award to a Stennis team in recognition of technical excellence in evaluating the operational anomalies and reliability improvements associated with the space shuttle engine cut-off system. Stennis employees receiving the award were: (standing, l to r) Freddie Douglas (NASA), George Drouant (Jacobs Technology Inc.), Fred Abell (Jacobs), Robert Drackett (Jacobs) and Mike Smiles (NASA); (seated, l to r): Binh Nguyen (Jacobs), Stennis Director Gene Goldman and Joseph Lacker (NASA). Phillip Hebert of NASA is not pictured.

  13. Front end for GPS receivers

    NASA Technical Reports Server (NTRS)

    Thomas, Jr., Jess Brooks (Inventor)

    1999-01-01

    The front end in GPS receivers has the functions of amplifying, down-converting, filtering and sampling the received signals. In the preferred embodiment, only two operations, A/D conversion and a sum, bring the signal from RF to filtered quadrature baseband samples. After amplification and filtering at RF, the L1 and L2 signals are each sampled at RF at a high selected subharmonic rate. The subharmonic sample rates are approximately 900 MHz for L1 and 982 MHz for L2. With the selected subharmonic sampling, the A/D conversion effectively down-converts the signal from RF to quadrature components at baseband. The resulting sample streams for L1 and L2 are each reduced to a lower rate with a digital filter, which becomes a straight sum in the simplest embodiment. The frequency subsystem can be very simple, only requiring the generation of a single reference frequency (e.g. 20.46 MHz minus a small offset) and the simple multiplication of this reference up to the subharmonic sample rates for L1 and L2. The small offset in the reference frequency serves the dual purpose of providing an advantageous offset in the down-converted carrier frequency and in the final baseband sample rate.

  14. Solar receiver with integrated optics

    NASA Astrophysics Data System (ADS)

    Jiang, Lun; Winston, Roland

    2012-10-01

    The current challenge for PV/Thermal (PV/T) systems is the reduction of radiation heat loss. Compared to solar thermal selective coating, the solar cells cannot be used as an efficient thermal absorber due to their large emissivity of the encapsulation material. Many commercial PV/T products therefore require a high concentration (more than 10x) to reach an acceptable thermal efficiency for their receivers. Such a concentration system inevitably has to track or semi-track, which induces additional cost and collects only the direct radiation from the sun. We propose a new PV/T design using a vacuum encapsulated thin film cell to solve this problem. The proposed design also collects the diffuse sun light efficiently by using an external compound parabolic concentrator (XCPC). Since the transparent electrode (TCO) of thin film cell is inherently transparent in visible light and reflective beyond infrared, this design uses this layer instead of the conventional solar cell encapsulation as the outmost heat loss surface. By integrating such a vacuum design with a tube shaped absorber, we reduce the complexity of conducting the heat energy and electricity out of the device. A low concentration standalone non-tracking solar collector is proposed in this paper. We also analyzed the thermosyphon system configuration using heat transfer and ray tracing models. The economics of such a receiver are presented.

  15. A cryogenic receiver for EPR.

    PubMed

    Narkowicz, R; Ogata, H; Reijerse, E; Suter, D

    2013-12-01

    Cryogenic probes have significantly increased the sensitivity of NMR. Here, we present a compact EPR receiver design capable of cryogenic operation. Compared to room temperature operation, it reduces the noise by a factor of ≈2.5. We discuss in detail the design and analyze the resulting noise performance. At low microwave power, the input noise density closely follows the emission of a cooled 50Ω resistor over the whole measurement range from 20K up to room temperature. To minimize the influence of the microwave source noise, we use high microwave efficiency (≈1.1-1.7mTW(-1/2)) planar microresonators. Their efficient conversion of microwave power to magnetic field permits EPR measurements with very low power levels, typically ranging from a few μW down to fractions of nW. PMID:24161681

  16. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... receivers. (a) If a medium frequency radiotelephone installation is provided, the receiver must be capable... kHz, and the receiving frequency(s) of public coast stations serving the area in which the vessel is... reception of H3E and J3E emissions on 2182 kHz and J3E emission on any receiving frequency...

  17. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... receivers. (a) If a medium frequency radiotelephone installation is provided, the receiver must be capable... kHz, and the receiving frequency(s) of public coast stations serving the area in which the vessel is... reception of H3E and J3E emissions on 2182 kHz and J3E emission on any receiving frequency...

  18. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... receivers. (a) If a medium frequency radiotelephone installation is provided, the receiver must be capable... kHz, and the receiving frequency(s) of public coast stations serving the area in which the vessel is... reception of H3E and J3E emissions on 2182 kHz and J3E emission on any receiving frequency...

  19. Development of an Air Brayton solar receiver

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Various receiver configurations and operating conditions were examined. The interface requirements between the receiver/concentrator/power module were addressed. Production cost estimates were obtained to determine the cost of the receiver during the 1980 timeframe. A conceptual design of an air Brayton solar receiver is presented based on the results. The following design goals were established: (1)peak thermal input power - 85 KWt; (2)receiver outlet air temperature - 1500 F; (3)receiver inlet air temperature - 1050 F; (4)design mass flow rate - 0.533 lb/sec; and (5)design receiver inlet pressure - 36.75 psia.

  20. Fluid absorption solar energy receiver

    NASA Technical Reports Server (NTRS)

    Bair, Edward J.

    1993-01-01

    A conventional solar dynamic system transmits solar energy to the flowing fluid of a thermodynamic cycle through structures which contain the gas and thermal energy storage material. Such a heat transfer mechanism dictates that the structure operate at a higher temperature than the fluid. This investigation reports on a fluid absorption receiver where only a part of the solar energy is transmitted to the structure. The other part is absorbed directly by the fluid. By proportioning these two heat transfer paths the energy to the structure can preheat the fluid, while the energy absorbed directly by the fluid raises the fluid to its final working temperature. The surface temperatures need not exceed the output temperature of the fluid. This makes the output temperature of the gas the maximum temperature in the system. The gas can have local maximum temperatures higher than the output working temperature. However local high temperatures are quickly equilibrated, and since the gas does not emit radiation, local high temperatures do not result in a radiative heat loss. Thermal radiation, thermal conductivity, and heat exchange with the gas all help equilibrate the surface temperature.

  1. Lunar Receiving Laboratory Project History

    NASA Technical Reports Server (NTRS)

    Mangus, Susan; Larsen, William

    2004-01-01

    As early as 1959, the Working Group on Lunar Exploration within NASA advocated that 'one of the prime objectives of the first lunar landing mission should be the collection of samples for return to Earth, where they could be subjected to detailed study and analysis.' Within NASA, neither this group nor any other scientists working with the Agency were concerned about back contamination issues. Outside of NASA, back contamination concerns had been raised as early as 1960. Although NASA did not seem to pay any attention to the concerns at that time, the scientific community continued to be interested in the topic. In 1962 and again in 1963, as the Apollo Program loomed large, further discussions were held. These early discussions of back contamination did not make their way into NASA's administration, however, and when Manned Spacecraft Center personnel began to articulate early concepts for the Lunar Receiving Laboratory (LRL), the back contamination issue was not considered. Once this concern became a major focus, however, the LRL's development became increasingly complex. This is the history of that development.

  2. Recent developments in superconducting receivers

    SciTech Connect

    Richards, P.L.

    1990-09-01

    A description is given of recent work at Berkeley on superconducting mixers and detectors for infrared and millimeter wavelengths. The first report is a review article which summarizes the status of development of superconducting components for infrared and millimeter wave receivers. The next report describes accurate measurements and also theoretical modeling of an SIS quasiparticle waveguide mixer for W-band which uses very high quality Ta junctions. The best mixer noise is only 1.3 times the quantum limit. Both the mixer gain and the noise are in quantitative agreement with the quantum theory. Next, a report is given on measurements and theoretical modeling of the absorptivity (surface resistance) of high quality epitaxial films of the high {Tc} superconductor YBCO from 750 GHz to 21 THz. Finally, there are reports on the design and experimental performance of two different types of high {Tc} bolometric detectors. One is a conventional bolometer with a gold-black absorber. The other is an antenna coupled microbolometer.

  3. Thermal resistance model for CSP central receivers

    NASA Astrophysics Data System (ADS)

    de Meyer, O. A. J.; Dinter, F.; Govender, S.

    2016-05-01

    The receiver design and heliostat field aiming strategy play a vital role in the heat transfer efficiency of the receiver. In molten salt external receivers, the common operating temperature of the heat transfer fluid or molten salt ranges between 285°C to 565°C. The optimum output temperature of 565°C is achieved by adjusting the mass flow rate of the molten salt through the receiver. The reflected solar radiation onto the receiver contributes to the temperature rise in the molten salt by means of heat transfer. By investigating published work on molten salt external receiver operating temperatures, corresponding receiver tube surface temperatures and heat losses, a model has been developed to obtain a detailed thermographic representation of the receiver. The steady state model uses a receiver flux map as input to determine: i) heat transfer fluid mass flow rate through the receiver to obtain the desired molten salt output temperature of 565°C, ii) receiver surface temperatures iii) receiver tube temperatures iv) receiver efficiency v) pressure drop across the receiver and vi) corresponding tube strain per panel.

  4. Structuring a sound securitization of healthcare receivables.

    PubMed

    Spradling, Mark

    2003-02-01

    Securitization of receivables allows healthcare providers to obtain an additional funding source by selling their accounts receivables to investors. A double-lock-box structure allows providers to securitize Medicare and Medicaid receivables without violating federal laws. A 2001 revision to the Uniform Commercial Code facilitates providers' securitization of private healthcare insurance receivables by underscoring rights of a purchaser of those receivables. HIPAA privacy standards appear to permit the use and disclosure of protected health information in crafting a securitization program. The securitization should be structured to shield the value of the receivables to be transferred from the potential backruptcies of the originator and the purchaser. PMID:12602313

  5. Percentage of Surgical Patients Receiving Recommended Care

    MedlinePlus

    ... Recommended Care Percentage of Surgical Patients Receiving Recommended Care This is a composite measure based on individual ... Age Group Percentage of Surgical Patients Receiving Recommended Care by Age Group uzrc-9bvr Download these data » ...

  6. 47 CFR 32.1170 - Receivables.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... demand or time notes, bills and drafts receivable, or other similar evidences (except interest coupons) of money receivable on demand or within a time not exceeding one year from date of issue. (d)...

  7. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Irwin, S. H.; NELSON; Roleyni, G.

    1977-01-01

    Optimal design studies of MLS angle-receivers and a theoretical design-study of MLS DME-receivers are reported. The angle-receiver results include an integration of the scan data processor and tracking filter components of the optimal receiver into a unified structure. An extensive simulation study comparing the performance of the optimal and threshold receivers in a wide variety of representative dynamical interference environments was made. The optimal receiver was generally superior. A simulation of the performance of the threshold and delay-and-compare receivers in various signal environments was performed. An analysis of combined errors due to lateral reflections from vertical structures with small differential path delays, specular ground reflections with neglible differential path delays, and thermal noise in the receivers is provided.

  8. Advanced solar receivers for space power

    NASA Technical Reports Server (NTRS)

    Strumpf, H. J.; Coombs, M. G.; Lacy, D. E.

    1988-01-01

    A study has been conducted to generate and evaluate advanced solar heat receiver concepts suitable for orbital application with Brayton and Stirling engine cycles in the 7-kW size range. The generated receiver designs have thermal storage capability and, when implemented, will be lighter, smaller, and/or more efficient than baseline systems such as the configuration used for the Brayton solar receiver under development by Garrett AiResearch for the NASA Space Station. In addition to the baseline designs, four other receiver concepts were designed and evaluated with respect to Brayton and Stirling engines. These concepts include a higher temperature version of the baseline receiver, a packed bed receiver, a plate-fin receiver, and a heat pipe receiver. The thermal storage for all designs is provided by the melting and freezing of a salt.

  9. Trough Receiver Heat Loss Testing (Presentation)

    SciTech Connect

    Lewandowski, A.; Feik, C.; Hansen, R.; Phillips, S.; Bingham, C.; Netter, J.; Forristal, R.; Burkholder, F.; Meglan, B.; Wolfrum, E.

    2006-02-01

    This presentation describes the design, fabrication, and qualification of an experimental capability for thermal loss testing of full-size trough receiver elements; and the testing on a variety of receivers.

  10. How To Improve You Shipping and Receiving.

    ERIC Educational Resources Information Center

    Sturgeon, Julie

    2001-01-01

    Discusses how two universities improved their shipping and receiving operations and cut costs. Examples from the University of Texas at Dallas and John Hopkins University, Baltimore, Maryland, illustrate how they established greater shipping and receiving department efficiencies. (GR)

  11. Telemetry Tests Of The Advanced Receiver II

    NASA Technical Reports Server (NTRS)

    Hinedi, Sami M.; Bevan, Roland P.; Marina, Miguel

    1993-01-01

    Report describes telemetry tests of Advanced Receiver II (ARX-II): digital radio receiving subsystem operating on intermediate-frequency output of another receiving subsystem called "multimission receiver" (MMR), detecting carrier, subcarrier, and data-symbol signals transmitted by spacecraft, and extracts Doppler information from signals. Analysis of data shows performance of MMR/ARX-II system comparable and sometimes superior to performances of Blk-III/BPA and Blk-III/SDA/SSA systems.

  12. Battle Keeps Solar Energy in Receiver

    NASA Technical Reports Server (NTRS)

    Mcdougal, A. R.; Hale, R. R.

    1982-01-01

    Mirror structure in solar concentrator reduces heat loss by reflection and reradiation. Baffle reflects entering rays back and forth in solar-concentrator receiver until they reach heat exchanger. Similarly, infrared energy reradiated by heat exchanger is prevented from leaving receiver. Surfaces of baffle and inside wall of receiver are polished and highly reflective at solar and infrared wavelengths.

  13. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  14. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  15. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  16. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Receiver. 80.1013 Section 80.1013 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be...

  17. 17 CFR 256.141 - Notes receivable.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... COMPANY ACT OF 1935 3. Current and Accrued Assets § 256.141 Notes receivable. This account shall include the cost of all notes receivable and similar evidences of amounts due within one year from persons... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Notes receivable....

  18. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  19. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  20. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  1. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  2. On board low noise 30 GHz receiver

    NASA Astrophysics Data System (ADS)

    Dambrosio, A.; Castelli, G.; Mazzini, C.

    An advanced receiver for onboard application in a 30/20 GHz SS-TDMA satellite communication system is described. The basic requirements of the receiver are a total noise temperature of 1000 K and a bandwidth of 250 MHz. Attention is given to system requirements, the receiver configuration, the parametric preamplifier, and the down converter and IF preamplifier.

  3. 49 CFR 393.88 - Television receivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Television receivers. 393.88 Section 393.88... NECESSARY FOR SAFE OPERATION Miscellaneous Parts and Accessories § 393.88 Television receivers. Any motor vehicle equipped with a television viewer, screen or other means of visually receiving a...

  4. 29 CFR 1917.155 - Air receivers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Air receivers. 1917.155 Section 1917.155 Labor Regulations...) MARINE TERMINALS Related Terminal Operations and Equipment § 1917.155 Air receivers. (a) Application. This section applies to compressed air receivers and equipment used for operations such as...

  5. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Highfill, J. H., III

    1979-01-01

    The angle tracking problems in microwave landing system receivers along with a receiver design capable of optimal performance in the multipath environments found in air terminal areas were studied. Included were various theoretical and evaluative studies like: (1) signal model development; (2) derivation of optimal receiver structures; and (3) development and use of computer simulations for receiver algorithm evaluation. The development of an experimental receiver for flight testing is presented. An overview of the work and summary of principal results and conclusions are reported.

  6. A minimalist approach to receiver architecture

    NASA Astrophysics Data System (ADS)

    Collins, O.

    1991-11-01

    New signal processing techniques are described for Deep Space Network radios and a proposed receiver architecture is presented, as well as experimental results on this new receiver's analog front end. The receiver's design employs direct downconversion rather than high speed digitization, and it is just as suitable for use as a space based probe relay receiver as it is for installation at a ground antenna. The advantages of having an inexpensive, shoe box size receiver, which could be carried around to antennas of opportunity, used for spacecraft testing or installed in the base of every antenna in a large array are the force behind this project.

  7. A minimalist approach to receiver architecture

    NASA Technical Reports Server (NTRS)

    Collins, O.

    1991-01-01

    New signal processing techniques are described for Deep Space Network radios and a proposed receiver architecture is presented, as well as experimental results on this new receiver's analog front end. The receiver's design employs direct downconversion rather than high speed digitization, and it is just as suitable for use as a space based probe relay receiver as it is for installation at a ground antenna. The advantages of having an inexpensive, shoe box size receiver, which could be carried around to antennas of opportunity, used for spacecraft testing or installed in the base of every antenna in a large array are the force behind this project.

  8. More Efficient Solar Thermal-Energy Receiver

    NASA Technical Reports Server (NTRS)

    Dustin, M. O.

    1987-01-01

    Thermal stresses and reradiation reduced. Improved design for solar thermal-energy receiver overcomes three major deficiencies of solar dynamic receivers described in literature. Concentrator and receiver part of solar-thermal-energy system. Receiver divided into radiation section and storage section. Concentrated solar radiation falls on boiling ends of heat pipes, which transmit heat to thermal-energy-storage medium. Receiver used in number of applications to produce thermal energy directly for use or to store thermal energy for subsequent use in heat engine.

  9. A zero-power radio receiver.

    SciTech Connect

    Brocato, Robert Wesley

    2004-09-01

    This report describes both a general methodology and some specific examples of passive radio receivers. A passive radio receiver uses no direct electrical power but makes sole use of the power available in the radio spectrum. These radio receivers are suitable as low data-rate receivers or passive alerting devices for standard, high power radio receivers. Some zero-power radio architectures exhibit significant improvements in range with the addition of very low power amplifiers or signal processing electronics. These ultra-low power radios are also discussed and compared to the purely zero-power approaches.

  10. Future GOES-R global ground receivers

    NASA Astrophysics Data System (ADS)

    Dafesh, P. A.; Grayver, E.

    2006-08-01

    The Aerospace Corporation has developed an end-to-end testbed to demonstrate a wide range of modern modulation and coding alternatives for future broadcast by the GOES-R Global Rebroadcast (GRB) system. In particular, this paper describes the development of a compact, low cost, flexible GRB digital receiver that was designed, implemented, fabricated, and tested as part of the development. This receiver demonstrates a 10-fold increase in data rate compared to the rate achievable by the current GOES generation, without a major impact on either cost or size. The digital receiver is integrated on a single PCI card with an FPGA device, and analog-to-digital converters. It supports a wide range of modulations (including 8-PSK and 16-QAM) and turbo coding. With appropriate FPGA firmware and software changes, it can also be configured to receive the current (legacy) GOES signals. The receiver has been validated by sending large image files over a high-fidelity satellite channel emulator, including a space-qualified power amplifier and a white noise source. The receiver is a key component of a future GOES-R weather receiver system (also called user terminal) that includes the antenna, low-noise amplifier, downconverter, filters, digital receiver, and receiver system software. This work describes this receiver proof of concept and its application to providing a very credible estimate of the impact of using modern modulation and coding techniques in the future GOES-R system.

  11. Integration Window Position Estimation in TR Receivers

    SciTech Connect

    Nekoogar, F; Dowla, F; Spiridon, A

    2005-03-15

    Transmitted-reference (TR) receivers avoid the stringent synchronization requirements that exist in conventional pulse detection schemes. However, the performance of such receivers is highly sensitive to precise timing acquisition and tracking as well as the length of their integration window. This window in TR receivers defines the limits of the finite integrator prior to the final decision making block. In this paper, we propose a novel technique that allows us to extract the timing information of the integration window very accurately in UWB-TR receivers in the presence of channel noise. The principles of the method are presented and the BER performance of a modified UWB-TR receiver is investigated by computer simulation. Our studies show that the proposed estimation technique adds value to the conventional TR receiver structure with modest increase in complexity.

  12. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Scanning receivers and frequency converters used with scanning receivers. 15.121 Section 15.121 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.121 Scanning receivers and frequency converters used with scanning receivers. (a)...

  13. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Scanning receivers and frequency converters used with scanning receivers. 15.121 Section 15.121 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.121 Scanning receivers and frequency converters used with scanning receivers. (a)...

  14. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Scanning receivers and frequency converters... GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.121 Scanning receivers and frequency... receivers and frequency converters designed or marketed for use with scanning receivers, shall: (1)...

  15. 47 CFR 15.121 - Scanning receivers and frequency converters used with scanning receivers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Scanning receivers and frequency converters... GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.121 Scanning receivers and frequency... receivers and frequency converters designed or marketed for use with scanning receivers, shall: (1)...

  16. The Caltech airborne submillimeter SIS receiver

    NASA Technical Reports Server (NTRS)

    Zmuidzinas, Jonas; Carlstrom, J.; Miller, D.; Ugras, N. G.

    1995-01-01

    We have constructed a sensitive submillimeter receiver for the NASA Kuiper Airborne Observatory (KAO) which at present operates in the 500-750 GHz band. The DSB receiver noise temperature is about 5 h nu/k(sub B) over the 500-700 GHz range. This receiver has been used to detect H2O(18)O, HCl, and CH in interstellar molecular clouds, and also to search for C(+) emission from the highly redshifted galaxy (z = 2.3) IRAS 10214.

  17. High-stability detectors for radioastronomical receivers

    NASA Astrophysics Data System (ADS)

    Teuber, Ute; Schmidt, Axel

    The increased bandwidths of radioastronomical receivers has increased the detector stability requirements. A detector with a short-term stability of 0.01 percent, required in a receiver with a 9 mm wavelength receiver, could not be achieved using previously available detectors and dc amplifiers. This paper describes a switched detector which meets these requirements, and presents resulting rms values as a function of integration time.

  18. Receiver System: Lessons Learned From Solar Two

    SciTech Connect

    LITWIN, ROBERT Z.; PACHECO, JAMES E.

    2002-03-01

    The Boeing Company fabricated the Solar Two receiver as a subcontractor for the Solar Two project. The receiver absorbed sunlight reflected from the heliostat field. A molten-nitrate-salt heat transfer fluid was pumped from a storage tank at grade level, heated from 290 to 565 C by the receiver mounted on top of a tower, then flowed back down into another storage tank. To make electricity, the hot salt was pumped through a steam generator to produce steam that powered a conventional Rankine steam turbine/generator. This evaluation identifies the most significant Solar Two receiver system lessons learned from the Mechanical Design, Instrumentation and Control, Panel Fabrication, Site Construction, Receiver System Operation, and Management from the perspective of the receiver designer/manufacturer. The lessons learned on the receiver system described here consist of two parts: the Problem and one or more identified Solutions. The appendix summarizes an inspection of the advanced receiver panel developed by Boeing that was installed and operated in the Solar Two receiver.

  19. DMSK Receiver For Mobile/Satellite Service

    NASA Technical Reports Server (NTRS)

    Davarian, Faramaz; Simon, Marvin K.; Sumida, Joe T.

    1989-01-01

    Receiver for 2.4-kbit/s differential minimum-shift keying (DMSK) and Gaussian minimum-shift keying(GMSK) suitable for communication between land-mobile stations via geostationary satellites. Operating on phase-shifted signal in 800-MHz band, in presence of fading and Doppler frequency shifts, receiver compact, makes efficient use of frequency spectrum, and wastes little power. Receiver design implemented in very-large-scale-integrated circuits. Basic DMSK receiver design relies on baseband rather than intermediate-frequency processing of in-phase and quadrature signal components because phase errors due to differential delays smaller at baseband.

  20. Ceramic high temperature receiver design and tests

    SciTech Connect

    Davis, S.B.

    1982-07-01

    The High Temperature Solar Thermal Receiver, which was tested a Edwards AFB, CA during the winter of 1980-1981, evolved from technologies developed over a five year period of work. This receiver was tested at the Army Solar Furnace at White Sands, NM in 1976. The receiver, was tested successfully at 1768 deg F and showed thermal efficiencies of 85%. The results were sufficiently promising to lead ERDA to fund our development and test of a 250 kW receiver to measure the efficiency of an open cavity receiver atop a central tower of a heliostat field. This receiver was required to be design scalable to 10, 50, and 100 MW-electric sizes to show applicability to central power tower receivers. That receiver employed rectangular silicon carbide panels and vertical stanchions to achieve scalability. The construction was shown to be fully scalable, and the receiver was operated at temperatures up to 2000 deg F to achieve the performance goals of the experiment during tests at the GIT advanced components test facility during the fall of 1978.

  1. Ceramic high temperature receiver design and tests

    NASA Technical Reports Server (NTRS)

    Davis, S. B.

    1982-01-01

    The High Temperature Solar Thermal Receiver, which was tested a Edwards AFB, CA during the winter of 1980-1981, evolved from technologies developed over a five year period of work. This receiver was tested at the Army Solar Furnace at White Sands, NM in 1976. The receiver, was tested successfully at 1768 deg F and showed thermal efficiencies of 85%. The results were sufficiently promising to lead ERDA to fund our development and test of a 250 kW receiver to measure the efficiency of an open cavity receiver atop a central tower of a heliostat field. This receiver was required to be design scalable to 10, 50, and 100 MW-electric sizes to show applicability to central power tower receivers. That receiver employed rectagular silicon carbide panels and vertical stanchions to achieve scalability. The construction was shown to be fully scalable; and the receiver was operated at temperatures up to 2000 deg F to achieve the performance goals of the experiment during tests at the GIT advanced components test facility during the fall of 1978.

  2. Receivers for the Microwave Radiometer on Juno

    NASA Technical Reports Server (NTRS)

    Maiwald, F.; Russell, D.; Dawson, D.; Hatch, W.; Brown, S.; Oswald, J.; Janssen, M.

    2009-01-01

    Six receivers for the MicroWave Radiometer (MWR) are currently under development at JPL. These receivers cover a frequency range of 0.6 to 22 GHz in approximately octave steps, with 4 % bandwidth. For calibration and diagnosis three noise diodes and a Dicke switch are integrated into each receiver. Each receiver is connected to its own antenna which is mounted with its bore sights perpendicular to the spin axis of the spacecraft. As the spacecraft spins at 2 RPM, the antenna field of view scans Jupiter's atmosphere from limb to nadir to limb, measuring microwave emission down to 1000-bar.

  3. Nursing process approach improves receivables management.

    PubMed

    Dias, K; Stockamp, D

    1992-09-01

    The "nursing process" is a systematic decision-making approach to problem solving based on open-system theory. This theory assumes that there is an on-going interchange between all system components. Components cannot be viewed in isolation, because decisions regarding one component will affect other components. Receivables management is similar to the nursing process, in that it involves constant diagnosis, assessment, and intervention in the work in process during all phases of the receivables cycle. In experiments that applied the nursing process concept to the management of accounts receivable in several hospitals, gross days in accounts receivable were reduced and cash flow was increased. PMID:10145682

  4. Optimization of MLS receivers for multipath environments

    NASA Technical Reports Server (NTRS)

    Mcalpine, G. A.; Highfill, J. H., III; Irwin, S. H.; Padgett, J. E.

    1975-01-01

    A receiver is designed for aircraft (A/C), which, as a component of the proposed Microwave Landing System (MLS), is capable of optimal performance in the multipath environments found in air terminal areas. Topics discussed include: the angle-tracking problem of the MLS receiver; signal modeling; preliminary approaches to optimal design; suboptimal design; and simulation study.

  5. The Information Processing Consequences of Receiver Apprehension.

    ERIC Educational Resources Information Center

    Preiss, Raymond W.; Rindo, John

    This paper discusses receiver apprehension, an information processing syndrome, in the context of counterattitudinal advocacy. Receiver apprehension was conceptualized as a trait anxiety associated with misinterpreting, inadequately processing, and/or being unable to adjust to incoming messages. This processing anxiety suggested cognitive rigidity…

  6. Liquid cooled fiber thermal radiation receiver

    DOEpatents

    Butler, Barry L.

    1987-01-01

    A radiation-to-thermal receiver apparatus for collecting radiation and converting it to thermal energy is disclosed. The invention includes a fibrous mat material which captures radiation striking the receiver. Captured radiation is removed from the fibrous mat material by a transparent fluid within which the material is bathed.

  7. Heat-Energy Analysis for Solar Receivers

    NASA Technical Reports Server (NTRS)

    Lansing, F. L.

    1982-01-01

    Heat-energy analysis program (HEAP) solves general heat-transfer problems, with some specific features that are "custom made" for analyzing solar receivers. Can be utilized not only to predict receiver performance under varying solar flux, ambient temperature and local heat-transfer rates but also to detect locations of hotspots and metallurgical difficulties and to predict performance sensitivity of neighboring component parameters.

  8. 47 CFR 80.1013 - Receiver.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Radiotelephone Installations Required by the Bridge-to-Bridge Act § 80.1013 Receiver. The bridge-to-bridge receiver must be capable of reception of G3E emission on the navigational frequency...

  9. Cashier/Accounts Receivable Clerk Exploration.

    ERIC Educational Resources Information Center

    Portsmouth City School Board, VA.

    The student materials present exercises designed to simulate the job performed by a cashier/accounts receivable clerk. The content of the course covers job instructions, writing receipts, proving cash, customer accounts, preparing statements, and schedule of accounts receivable. Also included in the document are a pretest and post test for the…

  10. 7 CFR 966.124 - Approved receiver.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TOMATOES GROWN IN FLORIDA Rules and..., as an approved receiver, tomatoes for purposes as set forth in § 966.120(a), shall annually, prior... specified purpose is to occur; (4) Whether or not the receiver packs, repacks or sells fresh tomatoes; (5)...

  11. 17 CFR 256.143 - Accounts receivable.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Accounts receivable. 256.143... SYSTEM OF ACCOUNTS FOR MUTUAL SERVICE COMPANIES AND SUBSIDIARY SERVICE COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 3. Current and Accrued Assets § 256.143 Accounts receivable. This account...

  12. 17 CFR 256.143 - Accounts receivable.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Accounts receivable. 256.143... SYSTEM OF ACCOUNTS FOR MUTUAL SERVICE COMPANIES AND SUBSIDIARY SERVICE COMPANIES, PUBLIC UTILITY HOLDING COMPANY ACT OF 1935 3. Current and Accrued Assets § 256.143 Accounts receivable. This account...

  13. Liquid cooled fiber thermal radiation receiver

    DOEpatents

    Butler, B.L.

    1985-03-29

    A radiation-to-thermal receiver apparatus for collecting radiation and converting it to thermal energy is disclosed. The invention includes a fibrous mat material which captures radiation striking the receiver. Captured radiation is removed from the fibrous mat material by a transparent fluid within which the material is bathed.

  14. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Radiotelephone receiver. 80.858 Section 80.858 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Technical Equipment Requirements for Cargo Vessels Not Subject to Subpart W § 80.858 Radiotelephone receiver. (a)...

  15. 47 CFR 80.913 - Radiotelephone receivers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Radiotelephone receivers. 80.913 Section 80.913 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Compulsory Radiotelephone Installations for Small Passenger Boats § 80.913 Radiotelephone receivers. (a) If a...

  16. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Radiotelephone receiver. 80.858 Section 80.858 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Technical Equipment Requirements for Cargo Vessels Not Subject to Subpart W § 80.858 Radiotelephone receiver. (a)...

  17. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... H3E and J3E emissions on the radiotelephone distress frequency. The receiver must be capable of... the distress frequency (2182 kHz) watch at the principal operating position and at any other place... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  18. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... H3E and J3E emissions on the radiotelephone distress frequency. The receiver must be capable of... the distress frequency (2182 kHz) watch at the principal operating position and at any other place... receiver input to produce an audio output of 50 milliwatts to the loudspeaker with a signal-to-noise...

  19. Advanced heat receiver conceptual design study

    NASA Technical Reports Server (NTRS)

    Kesseli, James; Saunders, Roger; Batchelder, Gary

    1988-01-01

    Solar Dynamic space power systems are candidate electrical power generating systems for future NASA missions. One of the key components of the solar dynamic power system is the solar receiver/thermal energy storage (TES) subsystem. Receiver development was conducted by NASA in the late 1960's and since then a very limited amount of work has been done in this area. Consequently the state of the art (SOA) receivers designed for the IOC space station are large and massive. The objective of the Advanced Heat Receiver Conceptual Design Study is to conceive and analyze advanced high temperature solar dynamic Brayton and Stirling receivers. The goal is to generate innovative receiver concepts that are half of the mass, smaller, and more efficient than the SOA. It is also necessary that these innovative receivers offer ease of manufacturing, less structural complexity and fewer thermal stress problems. Advanced Brayton and Stirling receiver storage units are proposed and analyzed in this study which can potentially meet these goals.

  20. 47 CFR 80.858 - Radiotelephone receiver.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the section must: (1) Have a sensitivity of 50 microvolts; (2) Be capable of operation when energized... showing the name of the receiver manufacturer and the type or model. (d) The sensitivity of a receiver is... of at least 6 decibels. Evidence of a manufacturer's rating or a demonstration of the sensitivity...

  1. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... designed to receive and display a television picture through broadcast, cable, or closed circuit television... parallel to the external surface of the receiver with an area of ten (10) square centimeters and no... from that component or circuit failure which maximizes x-radiation emissions. (4) Critical...

  2. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... designed to receive and display a television picture through broadcast, cable, or closed circuit television... parallel to the external surface of the receiver with an area of ten (10) square centimeters and no... from that component or circuit failure which maximizes x-radiation emissions. (4) Critical...

  3. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... designed to receive and display a television picture through broadcast, cable, or closed circuit television... parallel to the external surface of the receiver with an area of ten (10) square centimeters and no... from that component or circuit failure which maximizes x-radiation emissions. (4) Critical...

  4. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... designed to receive and display a television picture through broadcast, cable, or closed circuit television... parallel to the external surface of the receiver with an area of ten (10) square centimeters and no... from that component or circuit failure which maximizes x-radiation emissions. (4) Critical...

  5. 21 CFR 1020.10 - Television receivers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... designed to receive and display a television picture through broadcast, cable, or closed circuit television... parallel to the external surface of the receiver with an area of ten (10) square centimeters and no... from that component or circuit failure which maximizes x-radiation emissions. (4) Critical...

  6. 49 CFR 236.730 - Coil, receiver.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.730 Coil, receiver. Concentric layers of insulated wire wound around the core of a receiver of an automatic train stop, train control or cab signal device on a locomotive....

  7. A planar quasi-optical SIS receiver

    NASA Technical Reports Server (NTRS)

    Stimson, Philip A.; Dengler, Robert J.; Leduc, Henry G.; Cypher, Scott R.; Siegel, Peter H.

    1993-01-01

    A planar, quasi-optical SIS receiver operating at 230 GHz is described. The receiver consists of a 2 x 5 array of half wave dipole antennas with ten niobium-aluminum oxide-niobium SIS junctions on a quartz dielectric-filled parabola. The 1.4 GHz intermediate frequency is coupled from the mixer via coplanar strip transmission lines and 4:1 balun transformers. The receiver is operated at 4.2 K in a liquid helium immersion cryostat. We report accurate measurements of the performance of single receiver elements. A mixer noise temperature of 89 K DSB, receiver noise temperature of 156 K DSB, and conversion loss of 3 dB into a matched load have been obtained.

  8. High dynamic, low volume GPS receiver

    NASA Technical Reports Server (NTRS)

    Hurd, W. J.

    1983-01-01

    A new GPS receiver concept and design are presented to meet the high dynamic and low volume requirements for range applications in missiles and drones. The receiver has the potential to satisfy all range requirements with one basic receiver, which has significant potential economic benefit over the alternate approach of using a family of receivers, each tailored for specific applications. The main new concept is to use approximate maximum likelihood estimates of pseudo range and range-rate, rather than tracking with carrier phase locked loops and code delay locked loops. Preliminary analysis indicates that receivers accelerating at 50 g or more can track with position errors due to acceleration of approximately 0.2 m/g, or 10 m at 50 g. Implementation is almost entirely digital to meet the low volume requirements.

  9. EHF low-noise FET receiver

    NASA Technical Reports Server (NTRS)

    Schellenberg, J. M.; Watkins, E. T.

    1983-01-01

    Extremely high frequency (EHF) receivers for military and NASA programs must be small, lightweight, and highly reliable. In connection with recent advances in the development of mm-wave FET devices and circuits, a basis has been obtained for the eventual replacement of diode mixer front-ends by FET preamplifiers in receivers up to 94 GHz. By placing a low noise amplifier in front of the mixer it is possible to achieve a lower system noise figure than that found in conventional mm-wave receivers. A broader bandwidth can also be provided. Attention is given to the receiver configuration, a low noise FET amplifier, an image rejection filter, a dual-gate FET mixer, a FET local oscillator, and a FET receiver.

  10. Temperature influences in receiver clock modelling

    NASA Astrophysics Data System (ADS)

    Wang, Kan; Meindl, Michael; Rothacher, Markus; Schoenemann, Erik; Enderle, Werner

    2016-04-01

    In Precise Point Positioning (PPP), hardware delays at the receiver site (receiver, cables, antenna, …) are always difficult to be separated from the estimated receiver clock parameters. As a result, they are partially or fully contained in the estimated "apparent" clocks and will influence the deterministic and stochastic modelling of the receiver clock behaviour. In this contribution, using three years of data, the receiver clock corrections of a set of high-precision Hydrogen Masers (H-Masers) connected to stations of the ESA/ESOC network and the International GNSS Service (IGS) are firstly characterized concerning clock offsets, drifts, modified Allan deviations and stochastic parameters. In a second step, the apparent behaviour of the clocks is modelled with the help of a low-order polynomial and a known temperature coefficient (Weinbach, 2013). The correlations between the temperature and the hardware delays generated by different types of antennae are then analysed looking at daily, 3-day and weekly time intervals. The outcome of these analyses is crucial, if we intend to model the receiver clocks in the ground station network to improve the estimation of station-related parameters like coordinates, troposphere zenith delays and ambiguities. References: Weinbach, U. (2013) Feasibility and impact of receiver clock modeling in precise GPS data analysis. Dissertation, Leibniz Universität Hannover, Germany.