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Articles de revues sur le sujet "551..2"
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Ito, Makoto, Sumiaki Fukuda, Shohei Sakata, Hisayo Morinaga et Takeshi Ohta. « Pharmacological Effects of JTT-551, a Novel Protein Tyrosine Phosphatase 1B Inhibitor, in Diet-Induced Obesity Mice ». Journal of Diabetes Research 2014 (2014) : 1–7. http://dx.doi.org/10.1155/2014/680348.
Texte intégralRésumé :
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity.
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Gladstone, Douglas, Marc Andre, Jan Zaucha, Sarit Assouline, Naresh Bellam, Nicole Cascavilla, Eric Jourdan et al. « Results of a Phase 2 Study of MEDI-551 and Bendamustine Vs Rituximab and Bendamustine in Relapsed or Refractory Chronic Lymphocytic Leukemia ». Blood 124, no 21 (6 décembre 2014) : 4472. http://dx.doi.org/10.1182/blood.v124.21.4472.4472.
Texte intégralRésumé :
Abstract Background: In patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), novel therapies are needed to prolong disease control. MEDI-551, an afucoslylated, affinity-optimized, anti-CD19 antibody, functions by antibody-dependent cellular cytotoxicity, with a 30% monotherapy response rate in CLL. A phase 2 randomized, open-label study (NCT01466153) is evaluating the clinical activity, efficacy, and safety of combination therapy with MEDI-551 + bendamustine compared with rituximab + bendamustine in R/R CLL patients. Methods: Patients were initially randomized to receive bendamustine 70 mg/m2 intravenously (IV) on days 1, 2 with either MEDI-551 2 or 4 mg/kg on days 2, 8 of cycle 1 (on day 1 of subsequent cycles) or rituximab 375 mg/m2 IV on day 1 of cycle 1 (then 500 mg/m2 IV on day 2 of subsequent cycles), for up to six 28-day cycles. The 4-mg/kg dose of MEDI-551 was selected for the final efficacy analysis against rituximab. Safety assessments included adverse events (AEs) and laboratory parameters. Disease response was determined using 2008 International Working Group criteria. Exploratory objectives included micro RNA (miRNA) expression levels before and after treatment. Results: As of March 2014, the safety population comprised 147 patients across all treatment arms. The median age was 66 years (range 41–81), with 11% of patients with deletion (del) (17p), 20% with del (11q), 30% with del (13q), 12% with trisomy 12, and 39% with unmutated immunoglobulin heavy chains (IgVH). The median number of treatment cycles was 4 (range 1–6). Treatment-related AEs observed in ≥20% of patients included nausea, infusion-related reactions (IRRs), nausea, fatigue, pyrexia, neutropenia, and cough in the MEDI-551 arm vs nausea, fatigue, constipation, asthenia, pyrexia, and neutropenia in the rituximab arm. Grade 3/4 treatment-related AEs are listed in the table. Table. Treatment-Related Grade 3/4 AEs (≥5% of patients in any treatment group) Parameter, n (%) MEDI-551 + Bendamustine Rituximab + Bendamustine 2 mg/kg (n=32) 4 mg/kg (n=56) (n=59) Patients reporting ≥1 event 20 (63) 25 (45) 29 (49) Neutropenia 8 (25) 9 (16) 20 (34) IRR* 6 (19) 4 (7) 1 (2) Thrombocytopenia 2 (6) 1 (2) 5 (9) Lymphopenia 2 (6) 1 (2) 4 (7) Anemia 1 (3) 0 3 (5) Fatigue 0 0 3 (5) *Note: After 42 patients were enrolled in the study (all treatment groups), corticosteroid prophylaxis was recommended before patients receiving the initial dose of MEDI-551. Discontinuation of study treatment because of AEs occurred in 26% of patients receiving MEDI-551/bendamustine (including neutropenia, thrombocytopenia, bradycardia, abdominal pain, asthenia, fatigue, cytokine release syndrome, hypersensitivity, pneumonia, infusion-related reactions, elevated liver function tests, dehydration, hyponatremia, headache, depression, epistaxis, hypoxia, rash, and hypotension) and in 20% of those receiving rituximab/bendamustine (including febrile neutropenia, leukopenia, neutropenia, thrombocytopenia, cardiac failure, uveitis, small intestine obstruction, upper gastrointestinal hemorrhage, asthenia, fatigue, and systemic inflammatory response syndrome). No treatment-related deaths occurred in any treatment arm. Clinical activity was observed in both the MEDI-551 and rituximab arms, and a biomarker has been identified that may predict for MEDI-551 responders. Expression of a miRNA signature is specifically elevated in NHL patient samples. Low pretreatment levels of this miRNA signature in whole blood may predict for responders to MEDI-551. Three-fold lower levels (P<.0001) in pretreatment samples from MEDI-551 responders vs nonresponders were noted, but no differences in miRNA signature expression were noted between responders and nonresponders in the rituximab arm. Conclusions: Data show evidence of clinical activity in R/R CLL patients, with comparable safety observed between the MEDI-551 and rituximab arms. Expression level of a miRNA signature is able to predict for those more likely to respond to MEDI-551, with MEDI-551 responders having low pretreatment miRNA signature expression. Disclosures Gladstone: MedImmune: Research Funding. Andre:MedImmune: Research Funding. Zaucha:MedImmune: Research Funding. Assouline:MedImmune: Research Funding. Bellam:Genentech: Research Funding; Janssen: Research Funding; MedImmune: Research Funding; Facet: Research Funding. Cascavilla:MedImmune: Research Funding. Jourdan:MedImmune: Research Funding; Roche: Research Funding. Panwalkar:MedImmune: Research Funding. Patti:MedImmune: Research Funding. Zaja:MedImmune: Research Funding. Goswami:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Elgeioushi:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Streicher:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Bao:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Spaner:MedImmune: Research Funding.
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Forero-Torres, Andres, Mehdi Hamadani, Michelle A. Fanale, Celeste M. Bello, Thomas J. Kipps, Fritz Offner, Gregor Verhoef et al. « Safety Profile and Clinical Response To MEDI-551, a Humanized Monoclonal Anti-CD19, In a Phase 1/2 Study In Adults With Relapsed Or Refractory Advanced B-Cell Malignancies ». Blood 122, no 21 (15 novembre 2013) : 1810. http://dx.doi.org/10.1182/blood.v122.21.1810.1810.
Texte intégralRésumé :
Abstract Background MEDI-551 is an affinity-optimized and afucosylated humanized IgG kappa monoclonal antibody directed against CD19 and induces malignant clone destruction by antibody-dependent cellular cytotoxicity. This study evaluates the safety profile and clinical activity of MEDI-551 in patients with relapsed/refractory B-cell malignancies. These include chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM). Objectives Determine the safety profile and maximum tolerated dose (MTD) of MEDI-551 in patients with relapsed/refractory B-cell malignancies. Secondary objectives include clinical activity of MEDI-551. Methods In this phase 1/2 open-label multicenter, global dose-escalation and expansion study, patients with relapsed or refractory CLL, DLBCL, FL, or MM received MEDI-551 (at 0.5, 1, 2, 4, 8, or 12 mg/kg) by intravenous infusion administered over 28-day cycles using standard 3+3 dose escalation. Dose escalation continued to the maximum dose ≤12 mg/kg or until MTD was reached. Therapy continued for 2 cycles beyond complete response (CR), or until unacceptable toxicity or disease progression. Dose-limiting toxicity was defined as a MEDI-551-related adverse event (AE) that prevented completion of a full first cycle of MEDI-551, or as a ≥grade 3 toxicity (excluding hematologic toxicity) that could not be ascribed to another cause. Results Of 91 patients who received ≥1 dose of MEDI-551, 25 patients (CLL [3], DLBCL [6], FL [12], MM [4]) were enrolled in the phase 1 escalation portion (Jun 2010–Aug 2011). No MTD was achieved. The phase 2 expansion phase included 66 patients (CLL [23], DLBCL [20], FL [22], MM [1]) as of 14Jul2013. Three patients were re-treated with MEDI-551 upon relapse. Median age of patients treated was 66 years; median lines of prior therapy was 6. The median number of treatment cycles was 5 with a maximum of 28 cycles. There were 14 deaths due to AEs (none were drug-related) and 15 subjects discontinued treatment. One subject each discontinued due to drug-related neutropenia and infusion reaction. Most AEs were grade 1/2 with dose-independent frequency and severity (Table). Of 91 patients, 5 (5.5%) patients had grade 4 TEAEs (2 with drug-related neutropenia) and 9 (9.9%) had grade 5 events, none were drug related. Of 19 patients with 38 serious AEs (SAE), 2 patients had 3 events that were considered drug-related; pneumonia and sepsis in 1 patient and infusion related reaction in the other. Of 83 patients in the efficacy evaluable population (includes all patients who received any treatment of MEDI-551 and completed at least 1 post-baseline disease assessment), 9 had CR, 12 had partial responses (PR) and 42 had stable disease (SD; Figure 1). ORR to single-agent MEDI-551 was 24%, 24%, or 31% respectively in heavily pre-treated patients with CLL, DLBCL, or FL. Median progression-free survival was ≈9 months (Figure 2). Conclusions MEDI-551 has an acceptable safety profile warranting further study. Anti-tumor activity was achieved in a heavily pre-treated population of DLBCL, CLL, and FL patients respectively in this single-agent study. Phase 2 studies of MEDI-551 in combination with chemotherapy in DLBCL and CLL are ongoing. Funding Source This study was sponsored by MedImmune. Disclosures: Forero-Torres: MedImmune: Research Funding. Hamadani:MedImmune: Research Funding. Fanale:MedImmune: Research Funding. Bello:MedImmune: Research Funding. Kipps:MedImmune: Research Funding. Offner:MedImmune: Research Funding. Verhoef:MedImmune: Research Funding. Federico:MedImmune: Research Funding. Gregory:MedImmune: Research Funding. Sonet:MedImmune: Research Funding. Assouline:MedImmune: Research Funding. Pérez de Oteyza:MedImmune: Research Funding. Tomas:MedImmune: Research Funding. Cuneo:MedImmune: Research Funding. Elgeioushi:MedImmune: Employment, Stock/stock options from AstraZeneca Other. Goswami:MedImmune: Employment, Stock/stock options from AstraZeneca Other. Ibrahim:MedImmune: Employment, Stock/stock options from AstraZeneca Other. Herbst:MedImmune: Employment, Stock/stock options from AstraZeneca Other. Cheson:MedImmune: Research Funding.
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Forero, Andres, Mehdi Hamadani, Michelle A. Fanale, Celeste M. Bello, Thomas J. Kipps, Fritz Offner, Gregor Verhoef et al. « MEDI-551, a Humanized Monoclonal Anti-CD19, in Adults with Relapsed or Refractory Advanced B-Cell Malignancies : Results From a Phase 1/2 Study ». Blood 120, no 21 (16 novembre 2012) : 3677. http://dx.doi.org/10.1182/blood.v120.21.3677.3677.
Texte intégralRésumé :
Abstract Abstract 3677 Background: MEDI-551 is an affinity-optimized and afucosylated humanized IgG kappa monoclonal antibody directed against CD19 and induces malignant clone destruction by antibody-dependent cellular cytotoxicity. This study evaluates the safety and preliminary efficacy profile of MEDI-551 in patients with relapsed/refractory B-cell malignancies. These include chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM). Objectives: To determine the safety profile and maximum tolerated dose (MTD) or optimal biological dose of MEDI-551 in patients with relapsed/refractory B-cell malignancies. Secondary objectives include pharmacokinetics, immunogenicity, and clinical activity of MEDI-551. Methods: In this phase 1/2 open-label multicenter, global dose-escalation and expansion study, patients with relapsed or refractory CLL, DLBCL, FL, or MM received MEDI-551 (at 0.5, 1, 2, 4, 8, or 12 mg/kg) by intravenous infusion administered over 28-day cycles using standard 3+3 dose escalation. Dose escalation continued until the MTD (≤12 mg/kg) was reached. Therapy continued for 2 cycles beyond complete response (CR), or until unacceptable toxicity or disease progression. Dose-limiting toxicity was defined as a MEDI-551-related adverse event (AE) that prevented completion of a full first cycle of MEDI-551, or as a grade 3 or higher toxicity (excluding hematologic toxicity) that could not be ascribed to another cause, such as disease progression or accident. Results: Of the 63 patients (CLL [12], DLBCL [23], FL [23], MM [5]) who received ≥1 dose of MEDI-551, 25 patients (CLL [3], DLBCL [6], FL [12], MM [4]) were enrolled in the phase 1 escalation portion (Jun 2010–Aug 2011). No MTD was achieved. The phase 2 expansion phase is ongoing. Median age of patients treated was 62 years. The median of completed treatment cycles was 4.0 with a maximum of 15 cycles. Dose intensity was approximately 98%. There were 6 deaths due to AEs (none were drug-related) and 9 subjects discontinued treatment (2 [neutropenia and infusion site reaction] were nonserious drug-related AEs). Most AEs were grade 1/2 with dose-independent frequency and severity (Table). 13 patients had serious treatment-emergent adverse events (TEAEs); pneumonia, sepsis, and bacteremia in 1 patient were considered drug-related. 7 patients had grade 4 TEAEs (2 with neutropenia were drug-related) and 7 had grade 5 events, none related to drug. Of 43 patients in the evaluable for efficacy population (includes all patients who received any treatment of MEDI-551 and completed at least 1 post-baseline disease assessment), 5 had CR, 6 had partial responses (PR) and 21 had stable disease (SD; Figure 1). Median progression-free survival was ≈6 months (Figure 2). Conclusions: MEDI-551 demonstrated a safety profile warranting further study and no MTD was identified at the highest dose studied. The responses (CR: 11.6%; PR: 14.0%, objective response of 25.6% and SD of 48.8%) achieved in this single-agent study in heavily pretreated patients provide encouraging evidence of antitumor activity. Disclosures: Fanale: MedImmune: Research Funding. Kipps:MedImmune: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gregory:MedImmune (ALLRESEARCH FINDING PROCEEDS GO TO RUSH UVERSITY MEDICAL CENTER, NOT TOT ME PERSONALLY: Honoraria, Research Funding. Zhang:MedImmune: Employment. Goswami:MedImmune: Employment; AstraZeneca: Stocks, Stocks Other. Ibrahim:MedImmune: Employment; AstraZeneca: Stocks, Stocks Other. Yao:MedImmune: Employment. Herbst:MedImmune: Employment.
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Ogura, Michinori, Kiyoshi Ando, Naokuni Uike, Yoshiaki Ogawa, Toshiki Uchida, Yasunobu Abe, Takanobu Morishita et al. « A Multicenter Phase I Study of the Humanized Anti-CD19 Monoclonal Antibody, MEDI-551, in Patients with Relapsed or Refractory B-Cell Lymphoma and Multiple Myeloma ». Blood 124, no 21 (6 décembre 2014) : 1756. http://dx.doi.org/10.1182/blood.v124.21.1756.1756.
Texte intégralRésumé :
Abstract Background: MEDI-551 is an affinity-optimized and afucosylated humanized IgG kappa anti-CD19 monoclonal antibody enhanced for antibody-dependent cellular cytotoxicity. In a previous multicenter, phase 1/2 trial conducted in the United States and Europe, an overall disease control (objective response + stable disease) rate of 73.5% was achieved with MEDI-551 in patients (N=83) with relapsed or refractory B-cell malignancies, and median progression-free survival was 9.4 months (95% CI, 3.9–18.6 months) (Forero-Torres A, et al. 2013, ASH meeting). Objective: We conducted an open-label, multicenter, phase 1 dose escalation study of MEDI-551 in Japan in patients with relapsed or refractory B-cell lymphoma and myeloma to determine the safety profile, maximum tolerated dose (MTD) or optimal biologic dose (OBD), and the preliminary antitumor activity of MEDI-551. Methods: Patients aged 20 years or older with relapsed or refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or multiple myeloma (MM) were enrolled at 3 institutes in Japan. All patients received MEDI-551 (at 2, 4, or 8 mg/kg) intravenously on days 1 and 8 of the first 28-day cycle, then once every 28 days, with an additional dose cohort of 12 mg/kg added. Dose escalation continued to the maximum dose of 12 mg/kg or until MTD was reached. Therapy continued for 2 cycles after the achievement of complete response (CR) or until unacceptable toxicity or disease progression. Dose-limiting toxicity (DLT) was defined as a MEDI-551–related adverse event (AE) that inhibited completion of a full first cycle of MEDI-551, or as a grade ≥3 toxicity that could not be attributed to another cause. Results: From April 2011 through June 30, 2014, a total of 20 patients, including 6 with DLBCL, 11 with FL, 2 with CLL, and 1 with MM, received study treatment across 4 dose levels (2-mg/kg cohort; n=3; 4-mg/kg cohort, n=7; 8-mg/kg cohort, n=4; 12-mg/kg cohort, n=6). Two DLTs, including one infusion-related reaction and one case of neutropenia/leukopenia, were observed at the 12-mg/kg dose; thus, the MTD was determined to be 8 mg/kg. The AEs most commonly reported (in ≥15% of patients) were infusion-related reaction, hypertriglyceridemia, leukopenia, nasopharyngitis, decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and rash. A serious AE of epiglottitis (not treatment-related) was observed on day 64 after 4 cycles of MEDI-551 12-mg/kg. No treatment-related deaths were reported. Two patients with 12-mg/kg were discontinued due to treatment-related AEs (infusion-related reaction, decreased neutrophil count). Among 20 patients evaluable for response, 2 and 10 patients achieved CR and partial response, respectively, with an overall response rate of 60%. Six patients (30%) had stable disease. Response was obtained in 3/6 patients with DLBCL, 0/2 with CLL, 9/11 with FL, and 0/1 with MM, and in 2/3 at the MEDI-551 2-mg/kg dose, 3/7 at 4 mg/kg, 3/4 at 8 mg/kg, and 4/6 at 12 mg/kg. Data from this phase I study are being finalized. Conclusions: This phase I study demonstrated acceptable toxicity and preliminary but promising antitumor activity of MEDI-551, with an MTD of 8 mg/kg, in Japanese patients with relapsed or refractory DLBCL or FL. Disclosures Ogura: AstraZeneca: Research Funding; Pfizer: Research Funding; GSK: Research Funding; Eizai: Research Funding; Symbio: Research Funding; Kyowahakko-Kirin: Research Funding; Chugai: Research Funding; Zenyaku: Research Funding; Otsuka: Research Funding; Dainippon Sumitomo: Research Funding; Jansen: Research Funding; Soraisia: Research Funding; Mundi: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Ando:Kyowahakko-Kirin: Research Funding. Yagawa:AstraZeneca: Employment; AstraZeneca: Stock ownership, Stock ownership Other. Yokoi:AstraZeneca: Employment; AstraZeneca: Stock ownership, Stock ownership Other.
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Hamadani, Mehdi, Andres Forero, Thomas J. Kipps, Michelle A. Fanale, Antonio Cuneo, Jaime Perez de Oteyza, Douglas Gladstone et al. « MEDI-551, an anti-CD19 antibody active in chronic lymphocytic leukemia (CLL) patients previously treated with rituximab. » Journal of Clinical Oncology 31, no 15_suppl (20 mai 2013) : 7045. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.7045.
Texte intégralRésumé :
7045 Background: Anti-CD20 mAb therapy has provided survival advantage to patients (pts) with CLL; but pts invariably relapse after anti-CD20 therapy and new approaches are needed. The CLL cells of most pts express CD19, which are upregulated following anti-CD20 therapy. MEDI-551, an affinity-optimized anti-CD19 antibody, destroys malignant cells by Ab-dependent cellular cytotoxicity (ADCC) once bound to CD19. Methods: The activity and toxicity of single-agent MEDI-551 in CLL pts with prior rituximab administration was assessed in a phase 1/2, open-label, dose-escalation and expansion study (NCT00983619). Response was assessed using the 2008 Intl Working Group criteria. B-cell depletion was assessed with flow cytometry and confirmed with biomarker analyses (BAFF). Safety assessments included laboratory parameters and adverse events (AEs and serious AEs [SAEs]). Results: Of 91 pts with refractory B-cell malignancies included in the study, 26 had CLL. CLL pts had received a median of 6 prior therapies: 89% with chemotherapy, 27% with single-agent biologics. Within 3 cycles of MEDI-551 (3 mos), >60% of assessable pts achieved CD20+ B-cell depletion to <20 cell/uL. Decreases in circulating CD20+ and CD22+B cells were associated with concomitant increases in serum BAFF concentrations. Of 20 pts evaluable for response, 4 achieved partial response and 13 had stable disease. Commonly reported AEs were generally grade 1/2 and included infusion reactions (62%), nausea (23%), pyrexia (23%), and neutropenia (23%). Six SAEs were noted in 3 pts: 1 had infusion reaction and general health deterioration, another had subarachnoid hemorrhage (SAH), and a third had dyspnea, pyrexia, and back pain. Only infusion reaction was considered treatment related. Two treatment-unrelated events of general health deterioration and SAH resulted in death. Conclusions: Single-agent activity with a manageable toxicity profile was seen in CLL pts treated in this phase 1/2 study of MEDI-551. An ongoing phase 2 study of MEDI-551 in combination with bendamustine in relapsed CLL patients (NCT01466153) is evaluating clinical response to MEDI-551 and chemotherapy. This study was sponsored by MedImmune, LLC.
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Tordi, M. G., M. C. Silvestrini, A. Colosimo, L. Tuttobello et M. Brunori. « Cytochrome c-551 and azurin oxidation catalysed by Pseudomonas aeruginosa cytochrome oxidase. A steady-state kinetic study ». Biochemical Journal 230, no 3 (15 septembre 1985) : 797–805. http://dx.doi.org/10.1042/bj2300797.
Texte intégralRésumé :
The kinetics of oxidation of azurin and cytochrome c-551 catalysed by Pseudomonas aeruginosa cytochrome oxidase were re-investigated, and the steady-state parameters were evaluated by parametric and non-parametric methods. At low concentrations of substrates (e.g. less than or equal to 50 microM) the values obtained for Km and catalytic-centre activity are respectively 15 +/- 3 microM and 77 +/- 6 min-1 for azurin and 2.15 +/- 0.23 microM and 66 +/- 2 min-1 for cytochrome c-551, in general accord with previous reports assigning to cytochrome c-551 the higher affinity for the enzyme and to azurin a slightly higher catalytic rate. However, when the cytochrome c-551 concentration was extended well beyond the value of Km, the initial velocity increased, and eventually almost doubled at a substrate concentration greater than or equal to 100 microM. This result suggests a ‘half-hearted’ behaviour, since at relatively low cytochrome c-551 concentrations only one of the two identical binding sites of the dimeric enzyme seems to be catalytically active, possibly because of unfavourable interactions influencing the stability of the Michaelis-Menten complex at the second site. When reduced azurin and cytochrome c-551 are simultaneously exposed to Ps. aeruginosa cytochrome oxidase, the observed steady-state oxidation kinetics are complex, as expected in view of the rapid electron transfer between cytochrome c-551 and azurin in the free state. In spite of this complexity, it seems likely that a mechanism involving a simple competition between the two substrates for the same active site on the enzyme is operative. Addition of a chemically modified and redox inactive form of azurin (Hg-azurin) had no effect on the initial rate of oxidation of either azurin and cytochrome c-551, but clearly altered the time course of the overall process by removing, at least partially, the product inhibition. The results lead to the following conclusions: (i) reduced azurin and cytochrome c-551 bind at the same site on the enzyme, and thus compete; (ii) Hg-azurin binds at a regulatory site, competing with the product rather than the substrate; (iii) the two binding sites on the dimeric enzyme, though intrinsically equivalent, display unfavourable interactions. Since water is the product of the reduction of oxygen, point (iii) has important implications for the reaction mechanism.
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Streicher, Katie, Philip Brohawn, Mike Kuziora, Fernanda Pilataxi, Brandon Higgs, Kim Lehmann, Kathleen McKeever et al. « A microRNA Signature Predicts Response to Anti-CD19 Therapy (MEDI-551) in B-Cell Malignancies ». Blood 124, no 21 (6 décembre 2014) : 2198. http://dx.doi.org/10.1182/blood.v124.21.2198.2198.
Texte intégralRésumé :
Abstract Background: microRNAs (miRNA, miR) are a class of highly conserved short noncoding, 17–25 nucleotide long RNA products (Ambros; Nature, 2004) that regulate gene expression at the posttranscriptional level (Bartel; Cell, 2004). Specific miRNA expression signatures can distinguish cancer from benign tissues and may provide the basis for developing new diagnostic and therapeutic strategies (Nelson et al.; Mol Can Ther, 2008). Despite numerous studies focused on understanding the regulation of miRNA in cancer development and progression, the relationship between miRNA expression and response to B-cell therapy has not been fully explored; therefore, we sought to identify microRNAs that would identify patients with B cell malignancies who may derive improved benefit from MEDI-551, an afucosylated, affinity-optimized anti--CD19 antibody with enhanced antibody dependent cell cytotoxicity (ADCC). Methods: A miRNA signature was found to be highly differentially expressed between cell lines of high sensitivity (n = 4) versus low sensitivity (n = 3) to in vitro ADCC with MEDI-551. miRNA expression patterns were confirmed across four broad profiling platforms to ensure their reproducibility. This miRNA signature was pre-specified for testing in a Phase 1 and Phase 2 trials of MEDI-551 in B-cell malignancies to assess its clinical utility in predicting patient response to MEDI-551 treatment. For this analysis, quantitative PCR (TaqMan) was utilized on pre-treatment (baseline) whole blood or PBMC samples. Results: In patient samples, we found that the miRNA signature displayed consistent results between in vitro and in vivo experiments. The in vitro data showed a 12-fold (p < 0.001) lower median miRNA signature in cell lines highly sensitive to in vitro ADCC with MEDI-551 compared to those with lower sensitivity. In a Phase I trial evaluating multiple doses of MEDI-551, diffuse large B cell lymphoma (DLBCL) patients who responded to MEDI-551 (CR/PR, n = 5) had significantly lower (7-fold; p < 0.0001) median miRNA signature expression compared to patients who did not respond (PD, n = 10) (Figure 1). Similar results were observed in patients (n=34) with follicular lymphoma (FL) included in the Phase I trial and a Phase II trial for chronic lymphocytic leukemia (CLL) patients (n=160). Importantly, the microRNA signature did not appear to predict response to rituximab. Correlation of the miRNA signature with prognostic factors is covered in an abstract titled “MEDI-551 MicroRNA Signature is Not Correlated With Prognostic Markers in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia From a Phase 2 Study of MEDI-551 and Bendamustine vs Rituximab and Bendamustine.” To ensure that performance of the molecular test was sufficient for testing in a late stage clinical development, the original research assay was altered to make it more amenable to clinical testing and a validation plan was designed and executed to create a sensitive and specific miRNA signature test that demonstrated equivalence with the original assay utilized to evaluate clinical trial samples. Figure 1: miRNA signature expression is lower in DLBCL patient samples who respond to MEDI-551 compared to non-responders. Expression of the miRNA signature was evaluated in pre-treatment whole blood samples from DLBCL patients (n=26) enrolled in a Phase I trial by TaqMan qPCR and compared with expression in blood samples from healthy donors (n=13) to generate fold change values. Conclusions: Potential use of miRNA signatures as molecular biomarkers in human cancers is supported by a large body of literature, but their clinical implementation has been hindered by technical hurdles. Using cell lines with differing sensitivities to ADCC mediated by MEDI-551, we discovered a microRNA signature that correlates with response to MEDI-551.in Phase I and II clinical trials in patients with B-cell malignancies. This work, combined with the creation of an analytically validated miRNA signature test show promise as a potential predictive marker for response to MEDI-551. Additional larger trials will be necessary to confirm the utility of the microRNA signature as a potential companion diagnostic for MEDI-551 in the treatment of B cell malignancies. In addition, ongoing work is focused on gaining an understanding of the biological significance of this miRNA signature in B cell malignancies and its relationship to the mechanism of action for MEDI-551. Disclosures Streicher: MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Brohawn:MedImmune: Employment, Equity Ownership. Kuziora:MedImmune: Employment, Equity Ownership. Pilataxi:MedImmune: Employment, Equity Ownership. Higgs:MedImmune: Employment, Equity Ownership. Lehmann:MedImmune: Employment, Equity Ownership. McKeever:MedImmune: Employment, Equity Ownership. Goswami:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Herbst:MedImmune: Employment, Equity Ownership. Yao:MedImmune: Employment, Equity Ownership. Ranade:MedImmune: Employment, Equity Ownership.
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CUTRUZZOLÀ, Francesca, Ilaria CIABATTI, Gabriella ROLLI, Sabrina FALCINELLI, Marzia ARESE, Graziella RANGHINO, Andrea ANSELMINO, Elisabetta ZENNARO et Maria Chiara SILVESTRINI. « Expression and characterization of Pseudomonas aeruginosa cytochrome c-551 and two site-directed mutants : role of tryptophan 56 in the modulation of redox properties ». Biochemical Journal 322, no 1 (15 février 1997) : 35–42. http://dx.doi.org/10.1042/bj3220035.
Texte intégralRésumé :
The gene coding for Pseudomonas aeruginosacytochrome c-551 was expressed in Pseudomonas putidaunder aerobic conditions, using two different expression vectors; the more efficient proved to be pNM185, induced by m-toluate. Mature holo-(cytochrome c-551) was produced in high yield by this expression system, and was purified to homogeneity. Comparison of the recombinant wild-type protein with that purified from Ps. aeruginosashowed no differences in structural and functional properties. Trp56, an internal residue in cytochrome c-551, is located at hydrogen-bonding distance from haem propionate-17, together with Arg47. Ionization of propionate-17 was related to the observed pH-dependence of redox potential. The role of Trp56 in determining the redox properties of Ps. aeruginosacytochrome c-551 was assessed by site-directed mutagenesis, by substitution with Tyr (W56Y) and Phe (W56F). The W56Y mutant is similar to the wild-type cytochrome. On the other hand, the W56F mutant, although similar to the wild-type protein in spectral properties and electron donation to azurin, is characterized by a weakening of the FeŐMet61 bond, as shown in the oxidized protein by the loss of the 695 nm band approx. 2 pH units below the wild-type. Moreover, in W56F, the midpoint potential and its pH-dependence are both different from the wild-type. These results are consistent with the hypothesis that hydrogen-bonding to haem propionate-17 is important in modulation of the redox properties of Ps. aeruginosacytochrome c-551.
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Goswami, Trishna, Andres Forero, Mehdi Hamadani, Anne Sonet, Gregor Verhoef, Michelle A. Fanale, Celeste M. Bello, Wenmei Huang et Bruce D. Cheson. « Phase I/II study of MEDI-551, a humanized monoclonal antibody targeting CD19, in subjects with relapsed or refractory advanced B-cell malignancies. » Journal of Clinical Oncology 30, no 15_suppl (20 mai 2012) : 8065. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.8065.
Texte intégralRésumé :
8065 Background: Novel B-cell targeting agents, including monoclonal antibodies such as rituximab, are among recent advances in treatment of B-cell malignancies. New approaches are needed for patients progressing after rituximab-based therapies. MEDI-551 is an afucosylated monoclonal antibody targeting CD-19, a B-cell restricted transmembrane protein with enhanced affinity and antibody-dependent cellular cytotoxicity. Methods: Pts with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia, or multiple myeloma received single agent MEDI-551 at dosages ranging from 0.5 mg/kg to 12 mg/kg via intravenous infusion over 28-day cycles; cohorts 1-6 received 0.5, 1, 2, 4, 8, and 12 mg/kg, respectively. Results: 25 pts were enrolled in the phase I portion Jun 2010–Aug 2011. No maximum tolerated dose (MTD) was achieved. Most AEs were grade 1/2 with dose-independent frequency and severity (Table). Six pts had grade 3 toxicities including tumor lysis syndrome, infusion reaction, thrombocytopenia, and neutropenia, or grade 4 neutropenia. No grade 5 AEs were seen. All pts recovered. Three partial responses (PR) and 2 complete responses (CR) were seen in DLBCL and FL pts at 0.5, 4, and 8 mg/kg. Activity included a CR lasting 9 mo. in a FL pt in cohort 1, who is currently being retreated with MEDI-551 on relapse. Conclusions: MEDI-551 demonstrated a safety profile warranting further study and showed no MTD reached at the highest dose studied. Anti-tumor activity is suggested by the responses achieved across dose levels. Phase II is currently enrolling subjects. This study is funded by MedImmune, LLC. [Table: see text]
Thèses sur le sujet "551..2"
1
Coskun, Yelda. « Synthesis Of Conducting Polymers Of Terepthalic Acid Bis-(2-thiophen-3-yl-ethyl)ester And Investigation Of Their Electrochromic Properties ». Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/2/12605062/index.pdf.
Texte intégralRésumé :
Terepthalic acid bis-(2-thiophen-3-yl-ethyl)ester (TATE) was synthesized through the reaction of 2-thiophen-3-yl-ethanol and terepthaloyl chloride. Electrochemical behavior of the TATE and TATE in the presence of thiophene were studied by cyclic voltammetry (CV). The chemical structure of monomer is characterized via Nuclear Magnetic Resonance Spectroscopy (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Homopolymer of TATE was synthesized by galvanostatic and potentiostatic methods, and copolymerization of TATE with thiophene was achieved via potentiostatic method. Both homopolymer (PTATE) and copolymer [P(TATE-co-Th)] were characterized by various techniques including cyclic voltammetry, FTIR, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermal Gravimetry Analysis (TGA) and UV-VIS Spectrophotometer. Conductivities of samples were measured by four probe technique. Electronic band gap of polymers measured as the onset of the π
-&
#960
* transition using spectroelectrochemical analysis and colorimetry studies were investigated. Dual type polymer electrochromic devices (ECDs) based on PTATE, P(TATE-co-Th) and poly(3,4-ethylenedioxythiophene) (PEDOT) have been constructed. Spectroelectrochemistry, switching ability and stability of the devices were investigated by UV-Vis Spectrophotometer and Cyclic Voltammetry.
2
Köhler, Claas H. « Radiative Effect of Mixed Mineral Dust and Biomass Burning Aerosol in the Thermal Infrared ». Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-131635.
Texte intégralRésumé :
This thesis treats the optical properties of mixed mineral dust and biomass burning aerosol in the thermal infrared (TIR) based on Fourier Transform infrared spectrometer (FTIR) measurements and radiative transfer simulations. The measurements were part of the Saharan Mineral Dust Experiment 2 (SAMUM-2) conducted from January to February 2008 at Praia, Cape Verde. The large amount of different instruments co-located at the main field site during the campaign resulted in a unique dataset comprising in-situ information and remote sensing data perfectly suited for column closure studies. The ultimate goal of this work is to investigate the consistency of microphysical and TIR remote sensing data. This is achieved by reproducing the measured radiances at top and bottom of the atmosphere (TOA, BOA) with a radiative transfer model, which assimilates the microphysical aerosol information gathered during SAMUM-2.
The first part of the thesis describes several experimental efforts, including a novel calibration method and a drift correction algorithm for the ground-based FTIR instrument operated within the scope of SAMUM-2 by the author. The second part introduces the concurrent radiative transfer library PIRATES, which has been developed in the framework of this thesis for the analysis of TIR aerosol optical properties. The third and final part of the treatise compares measured and simulated spectra for various typical scenarios encountered during SAMUM-2.
It is demonstrated in three case studies, that measured radiances in the TIR atmospheric window region (8-12 µm) can be reproduced at BOA and TOA by radiative transfer simulations assuming spheroidal model particles. Moreover,
spherical particles are shown to be an inadequate model for mineral dust aerosol
in this spectral region unless the aerosol optical depth is small.
3
Meredith, David. « 2-D and 3-D computer modelling of lithosphere dynamics and sedimentary basin formation ». Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288437.
Texte intégral
4
Leclère, Henri. « Comportement sismo-mécanique des failles crustales et interactions fluides-séismes : Une étude de la région de l'Ubaye (Alpes du sud) combinant sismologie, géologie structurale, pétrophysique et modélisation numérique ». Electronic Thesis or Diss., Besançon, 2012. http://www.theses.fr/2012BESA2044.
Texte intégralRésumé :
Ce travail s'intéresse à l'étude du comportement en conditions statiques des failles dans la croûte supérieure continentale et plus particulièrement à l'effet des surpressions de fluides sur la réactivation des failles et le déclenchement des séismes. Pour ce faire, une analyse associant sismologie, géologie structurale, pétrophysique, géochimie et modélisation hydromécanique a été menée dans la région de l'Ubaye (Alpes du sud) où a eu lieu, en 2003-2004, un essaim sismique en relation avec des failles régionales affleurant plus au sud dans le massif cristallin de l'Argentera. Les mécanismes au foyer de 74 événements de cet essaim sismique ont été déterminés. À partir de ces mécanismes et d'autres données sismologiques ainsi que de modèles mécaniques basés sur la théorie de Mohr-Coulomb, cette étude a permis de confirmer que l'activité sismique de l'essaim était liée à la présence de surpressions de fluides et d'expliquer l'évolution spatio-temporelle des surpressions. Un modèle hydromécanique est proposé afin de concilier les évolutions spatio-temporelles de la sismicité et des surpressions de fluides. L'étude d'un affleurement d'une faille régionale de l'Argentera combinant analyse structurale, mesures pétrophysiques et modélisation hydromécanique a ensuite permis de préciser le comportement hydromécanique des failles aux profondeurs hypocentrales et plus particulièrement leur capacité à être compactées et à développer des surpressions de fluides. Finalement, l'initiation des séismes à la base de la zone sismogénique est explorée à partir d'analyses géochimiques et mécaniques menées sur de veines à paragénèse quartz-chlorite formées à la base de la zone sismogène. Ces résultats sont comparés avec ceux déduits de l'analyse de l'essaim sismique de l'Ubaye. Ce travail a permis d'étudier le comportement sismomécanique des failles et les interactions entre failles, fluides et séismes à travers la zone sismogène. Il met l'accent sur l'importance de coupler les approches sismologiques, hydrauliques et mécaniques dans l'étude des failles activesThis work adresses the behavior of faults in the upper continental crust under static conditions and moreparticularly the effect of fluid overpressures on fault reactivation and earthquake triggering. In order toreach this goal, an analysis combining seismology, structural geology, petrophysics, geochemistry andhydromechanical modeling has been carried out in the Ubaye region (southern French-Italian Alps) wherea seismic swarm related to regional faults exposed in the Argentera basement massif (located furthersouth) occurred in 2003-2004. Focal mechanisms of 74 events from this seismic swarm have beendetermined. Based on these mechanisms and other seismological data and on mechanical modeling basedon the Mohr-Coulomb theory, this study allows to confirm that the seismic activity of the swarm waslinked to the presence of overpressurized fluids and to explain the spatio-temporal evolution ofoverpressures. A hydromechanical model is proposed in order to account for the spatio-temporalevolutions of both seismicity and pore fluid overpressures. The study of an exposure of an Argenteraregional fault combining a structural analysis, petrophysical measurements and a hydromechanicalmodeling has allowed to decipher the hydromechanical behavior of faults at hypocentral depths, and moreparticularly to determine the ability of faults to be compacted and to develop fluid overpressures. Lastly,the initiation of earthquakes at or near the base of the seismogenic zone is explored through geochemicaland mechanical analyses of quartz-chlorite veins formed at the base of the seismogenic zone. Theseresults are then compared with those deduced from the analysis of the Ubaye seismic swarm. This workallows to study the seismo-mechanical behavior of faults and the interactions between faults, fluids andearthquakes across the seismogenic zone. It emphasizes the importance of associating seismological,hydraulic et mechanical analyses in the study of active faults
5
Weithäuser, Ina, Gunter Stober, Kristina Fröhlich et Christoph Jacobi. « Untersuchung der Quasi - 2 - Tage Welle im Sommer 2005 ». Universität Leipzig, 2007. https://ul.qucosa.de/id/qucosa%3A15568.
Texte intégralRésumé :
Das seit Juli 2004 kontinuierlich arbeitende Meteorradar am Observatorium Collm (53,3°N, 13°E) der Universität Leipzig dient der Messung des horizontalen Windfeldes sowie der Temperatur in der Mesopausenregion. Neben der Betrachtung des jahreszeitlichen Verhaltens von Grund- und Gezeitenwind ist es möglich, die Aktivität planetarer Wellen zu untersuchen. Spezielles Interesse gilt dabei der Quasi-2-Tage Welle im Sommer 2005, da zu dieser Zeit sowohl eine Verschiebung der maximalen Amplituden hin zu kürzeren als auch zu längeren Perioden beobachtbar war. Als mögliche Ursache dafür werden nichtlineare Wechselwirkungen zwischen der Quasi-2-Tage Welle und planetaren Wellen mit größeren Perioden gesehen. Die Untersuchung derartiger Wechselwirkungen erfolgt mit Hilfe der Bispektralanalyse.Since July 2004 the meteor radar operates continuously at the Observatory (53,3°N, 13°E) of the University of Leipzig. It provides data of the horizontal wind field as well as the temperature of the mesopause region. In addition to the consideration of the seasonal behaviour of prevailing and tidal winds it is possible to examine the activity of planetary waves. Because of the shift of maximum amplitudes of the quasi-2-day wave in summer 2005 to shorter as well as longer periods the event has to be considered more in detail. Possible reasons for the displacements are nonlinear couplings between the quasi-2-day wave and planetary waves with longer periods. The examination of those couplings is performed using bispectral analyses.
6
Trautmann, Thomas, et Andreas Bott. « Ein numerisches Modell zur lokalen Nebelvorhersage. Teil 2 : Behandlung von Erdboden und Vegetation ». Universität Leipzig, 2002. https://ul.qucosa.de/id/qucosa%3A15216.
Texte intégralRésumé :
Die im Nebelvorhersagemodell PAFOG enthaltenen Modellkomponenten für parametrisierte Wolkenphysik, Strahlung und Sichtweitenbestimmung wurden durch Module zur Beschreibung der Interaktion mit dem Boden und der Vegetation ergänzt. Das auf diese
Weise komplettierte Modellsystem PAFOG-V kann dazu verwendet werden, das lokale Auftreten von Strahlungsnebel und niedriger stratiformer Bewölkung vorherzusagen.The paper presents an extension of the model components for parameterized cloud physics, radiation and visibility determination as implemented in the local forecast model PAFOG to include the interaction with the soil and the vegetation. The resulting forecast system PAFOG-V can be used to predict local events of radiation fogs and of low level stratiform clouds.
7
Nadin, P. A. « Cretaceous-tertiary post-rift subsidence across the NE Atlantic margin : an analysis using quantitative 2-D and reverse stratigraphic modelling ». Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283040.
Texte intégral
8
Jacobi, Christoph, Rudolf Schminder et Dierk Kürschner. « Long-period (2-18 Days) oscillations of mesopause winds at Collm ». Wissenschaftliche Mitteilungen des Leipziger Instituts für Meteorologie ; 4 = Meteorologische Arbeiten aus Leipzig ; 2 (1996), S. 131-143, 1996. https://ul.qucosa.de/id/qucosa%3A15060.
Texte intégralRésumé :
Daily analyses of the zonal and meridional prevailing wind at the mesopause ( - 95 km height) are investigated with respect to planetary wave scale oscillations with periods ranging between 2 and 18 days. A mean climatology of the years 1983 - 1994 is presented. Time series of planetary wave activity show a significant increase during this period, which is in accordance with results from literature.Tägliche Analysen des zonalen und meridionalen Grundwindes in der Mesopausenregion (- 95 km Höhe) werden hinsichtlich planetarer Wellenaktivität im Periodenbereich von 2 bis 18 Tagen untersucht. Es wird eine mittlere Klimatologie der Jahre 1983 - 1994 dargestellt. In diesem Zeitraum ist eine signifikante Zunahme der Wellenaktivität zu verzeichnen, die in Übereinstimmung mit Literaturangaben steht.
9
Trautmann, Thomas, et Andreas Bott. « Ein numerisches Modell zur lokalen Nebelvorhersage. Teil 2 : Behandlung von Erdboden und Vegetation ». Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-216944.
Texte intégralRésumé :
Die im Nebelvorhersagemodell PAFOG enthaltenen Modellkomponenten für parametrisierte Wolkenphysik, Strahlung und Sichtweitenbestimmung wurden durch Module zur Beschreibung der Interaktion mit dem Boden und der Vegetation ergänzt. Das auf diese Weise komplettierte Modellsystem PAFOG-V kann dazu verwendet werden, das lokale Auftreten von Strahlungsnebel und niedriger stratiformer Bewölkung vorherzusagenThe paper presents an extension of the model components for parameterized cloud physics, radiation and visibility determination as implemented in the local forecast model PAFOG to include the interaction with the soil and the vegetation. The resulting forecast system PAFOG-V can be used to predict local events of radiation fogs and of low level stratiform clouds
10
Weithäuser, Ina, Gunter Stober, Kristina Fröhlich et Christoph Jacobi. « Untersuchung der Quasi - 2 - Tage Welle im Sommer 2005 ». Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-223188.
Texte intégralRésumé :
Das seit Juli 2004 kontinuierlich arbeitende Meteorradar am Observatorium Collm (53,3°N, 13°E) der Universität Leipzig dient der Messung des horizontalen Windfeldes sowie der Temperatur in der Mesopausenregion. Neben der Betrachtung des jahreszeitlichen Verhaltens von Grund- und Gezeitenwind ist es möglich, die Aktivität planetarer Wellen zu untersuchen. Spezielles Interesse gilt dabei der Quasi-2-Tage Welle im Sommer 2005, da zu dieser Zeit sowohl eine Verschiebung der maximalen Amplituden hin zu kürzeren als auch zu längeren Perioden beobachtbar war. Als mögliche Ursache dafür werden nichtlineare Wechselwirkungen zwischen der Quasi-2-Tage Welle und planetaren Wellen mit größeren Perioden gesehen. Die Untersuchung derartiger Wechselwirkungen erfolgt mit Hilfe der BispektralanalyseSince July 2004 the meteor radar operates continuously at the Observatory (53,3°N, 13°E) of the University of Leipzig. It provides data of the horizontal wind field as well as the temperature of the mesopause region. In addition to the consideration of the seasonal behaviour of prevailing and tidal winds it is possible to examine the activity of planetary waves. Because of the shift of maximum amplitudes of the quasi-2-day wave in summer 2005 to shorter as well as longer periods the event has to be considered more in detail. Possible reasons for the displacements are nonlinear couplings between the quasi-2-day wave and planetary waves with longer periods. The examination of those couplings is performed using bispectral analyses
Livres sur le sujet "551..2"
1
Christine, Becker, et Hauptverband der Gewerblichen Berufsgenossenschaften (Germany), dir. Erfahrungen mit der Anwendung von [Paragraph] 551 Abs. 2 RVO bei beruflichen Erkrankungen. 2e éd. Sankt Augustin : Hauptverband der Gewerblichen Berufsgenossenschaften, 1989.
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2
United States. Congress. Senate. Committee on Foreign Relations, dir. 106-2 Hearing : The Legacies of The Holocaust, S. Hrg. 106-551, April 5, 2000. [S.l : s.n., 2000.
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3
United States. Congress. Senate. Committee on Foreign Relations, dir. 106-2 Hearing : The Legacies of The Holocaust, S. Hrg. 106-551, April 5, 2000. [S.l : s.n., 2000.
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4
United States. Congress. Senate. Committee on Foreign Relations., dir. 106-2 Hearing : The Legacies of The Holocaust, S. Hrg. 106-551, April 5, 2000. [S.l : s.n., 2000.
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5
United States. Congress. Senate. Committee on Foreign Relations, dir. 106-2 Hearing : The Legacies of The Holocaust, S. Hrg. 106-551, April 5, 2000. [S.l : s.n., 2000.
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6
Гаман, В. І один в ЦК воїн. У політиці друзів не буває. Київ : Логос, 2005.
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7
McGilloway, D. A., dir. Grassland : a global resource. The Netherlands : Wageningen Academic Publishers, 2005. http://dx.doi.org/10.3920/978-90-8686-551-2.
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Mulvenna, Maurice D., et Chris D. Nugent, dir. Supporting People with Dementia Using Pervasive Health Technologies. London : Springer London, 2010. http://dx.doi.org/10.1007/978-1-84882-551-2.
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Oliveira, Antonella Carvalho de, dir. Coleção desafios das engenharias : Engenharia de materiais e metalúrgica 2 : -. Brazil : Atena Editora, 2021.
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106-2 Hearing : The Legacies of The Holocaust, S. Hrg. 106-551, April 5, 2000. [S.l : s.n., 2000.
Trouver le texte intégralChapitres de livres sur le sujet "551..2"
1
Hamacher, E. « Entstehungsgeschichte und Fortentwicklung nach § 551 Abs. 2 RVO ». Dans Gutachtenkolloquium 3, 163–68. Berlin, Heidelberg : Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73550-9_24.
Texte intégral
2
Bauers, G. « Erweiterung der BK Nr. 2102 nach § 551 Abs. 2 RVO — Arbeitstechnische Voraussetzungen — ». Dans Gutachtenkolloquium 3, 175–83. Berlin, Heidelberg : Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73550-9_26.
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3
Greinemann, H. « Erweiterung der BK Nr. 2102 nach § 551 Abs. 2 RVO — Medizinische Voraussetzungen — ». Dans Gutachtenkolloquium 3, 195–203. Berlin, Heidelberg : Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73550-9_28.
Texte intégral
4
Oh-oka, Hirozo, Saki Kakutani, Shoichiro Kamei, Hiroshi Matsubara, Masayo Iwaki et Shigeru Itoh. « Photoactive Reaction Center (PscA/Cytochrome c 551)2 Complex of Chlorobium limicola ». Dans Photosynthesis : from Light to Biosphere, 1061–64. Dordrecht : Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-009-0173-5_250.
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Bonnermann, R. « Erweiterung der BK Nr. 2102 nach § 551 Abs. 2 RVO — Erste Erfahrungen aus der Sicht der Verwaltung — ». Dans Gutachtenkolloquium 3, 185–93. Berlin, Heidelberg : Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-73550-9_27.
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Demaison, J. « 551 C5H9F3O2 1,4-Dioxane - trifluoromethane (1/1) ». Dans Asymmetric Top Molecules. Part 2, 511. Berlin, Heidelberg : Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-10400-8_299.
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7
Alexander IV. « 551 Anagni, 1256 Sept. 2 ». Dans Original Papal Documents in England and Wales from the Accession of Pope Innocent III to the Death of Pope Benedict XI (1198–1304), sous la direction de Jane E. Sayers. Oxford University Press, 1999. http://dx.doi.org/10.1093/oseo/instance.00255019.
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« I.79 39.7 Aug.2°,fol.551 EBRIETAS. Wem Trunckenheit gefeit ». Dans Ethica. Physica, 176–77. De Gruyter, 1985. http://dx.doi.org/10.1515/9783112695661-080.
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Kraus, Rob, Brian Barber, Mike Borkin et Naomi J. Alpern. « Exchange Server – Mail Service Attacks ». Dans Seven Deadliest Microsoft Attacks, 71–92. Elsevier, 2010. http://dx.doi.org/10.1016/b978-1-59749-551-6.00004-2.
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Nugus, Sue. « Selecting and Evaluating Forecasting Techniques ». Dans Financial Planning Using Excel, 93–100. Elsevier, 2009. http://dx.doi.org/10.1016/b978-1-85617-551-7.00008-2.
Texte intégralActes de conférences sur le sujet "551..2"
1
Tong, F., R. M. Macfarlane, W. P. Risk et Wilfred Lenth. « A 551-nm diode laser pumped upconversion laser ». Dans OSA Annual Meeting. Washington, D.C. : Optica Publishing Group, 1989. http://dx.doi.org/10.1364/oam.1989.fp1.
Texte intégralRésumé :
There have recently been several reports of visible upconversion lasers that are pumped by cw dye lasers.1,2 We report the first operation to our knowledge of an upconversion laser pumped by a semiconductor diode laser. Using a GaAlAs diode laser array as the pump source, upconversion lasing at 551 nm was observed in LiYF4:Er3+ (5%) at 41 K. The ~791-nm pump light populates the long-lived (~5 ms) intermediate 4I11/2 state of Er3+ and an efficient energy transfer upconversion process involving two ions in 4I11/2 results in excitation of the 4S3/2 upper laser level. When the near infrared pump laser was turned off rapidly the green laser continued to oscillate for several hundred microseconds, demonstrating that upconversion pumping occurs predominantly by energy transfer rather than sequential two-photon absorption. The relatively poor spectral overlap of the multimode output spectrum (~3-nm band-width) of the laser array and the 0.8-nm wide Er3+ absorption lines resulted in only 15% absorption of the pump light in the 3mm long laser crystal which had mirror coatings directly deposited on spherically polished faces. As a consequence, the pump threshold of 225 mW of incident diode laser power was relatively high; with 340 mW of pump power the green output was 100 µW. A much lower pump threshold of 13 mW of incident power was observed with a cw near infrared narrowband dye laser. With 130 mW of dye laser power a 551-nm output of 4.2 mW was achieved. This latter result suggests the use of index guided single-mode GaAlAs diode lasers for efficient pumping of erbium upconversion lasers.
2
Pollnau, M., E. Heumann, F. Heine, T. Danger, W. Lüthy, G. Huber et H. P. Weber. « Population mechanisms of the roomtemperature 551 nm Er:LiYF4 laser ». Dans The European Conference on Lasers and Electro-Optics. Washington, D.C. : Optica Publishing Group, 1994. http://dx.doi.org/10.1364/cleo_europe.1994.ctuk65.
Texte intégralRésumé :
One of the interests in solid-state laser physics has focused on diode-pumped blue and green upconversion lasers. At 551 nm upconversion-pumped laser operation in Er3+:LiYF4 at cryogenic temperatures has been reported, see e.g., Ref. 1. Recently room-temperature lasing under different excitation schemes has been achieved.2,3 However, the population and deexcitation processes of the upper laser level as well as the influence of reabsorption on the laser wavelength4 have not yet been quantitatively understood. In this paper the results of a computer simulation of the Er3+:LiYF4 laser are reported. The rate-equation scheme considers all excited levels up to 2H9/2, ground-state depletion, excited-state absorption (ESA) on the pump and laser wavelength, three upconversion processes, stimulated emission, and a realistic resonator design. From the computer simulation the population mechanisms of the laser system are analyzed and suggestions for a better laser performance are derived.
3
Macfarlane, R. M., E. A. Whittaker et W. Lenth. « Blue, yellow, and green upconversion lasing in Er:YLF using 1.5 μm pumping ». Dans OSA Annual Meeting. Washington, D.C. : Optica Publishing Group, 1992. http://dx.doi.org/10.1364/oam.1992.tuf1.
Texte intégralRésumé :
We have shown that multiple-step upconversion pumping of Er:YLiF4 at 1.50 μm into the metastable 4I13/12 level excites blue (469.7 nm), yellow (560.6 nm), and green (551 nm) laser emission from the 2P3/2,2H9/2, and 4S3/2 levels, respectively. This requires the energy of at least five erbium ions pumped into 4I13/2 to populate the upper level for the blue transition, four for the yellow, and three for the green. We believe that the mechanism for upconversion consists of a sequence of pairwise energy transfer steps involving several metastable excited levels. Monolithic laser crystals, ~3 mm long and doped with 1% Er3+, were prepared with mirrors applied directly to the crystal surfaces. The thresholds for laser action were 25 mW, 50 mW, and 80 mW for the yellow, green, and blue lasers, respectively. This shows that high order excitation processes in upconversion lasers involving long lived (here ~10 ms) metastable levels can be rather efficient. Output powers of these lasers at 30 K reached 10 mW at 551 nm for 350 mW of pump light, 10 mW at 560.6 nm for 140 mW of pump light, and 0.7 mW at 469.7 nm for 350 mW of pump light. Given the quantum defect between the input and output photons, these are good overall efficiencies. Lasing was observed up to 80 K. This work extends an earlier study,1 in which we obtained upconversion laser output at the three wavelengths by pumping in the near IR at 0.80 μm and 0.97 μm, to the observation of even higher order upconversion processes.
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« APPLICATION OF THE ADMINISTRATIVE PROCEDURE FOR THE PROTECTION OF CIVIL RIGHTS AND FREEDOMS ». Dans Russian science : actual researches and developments. Samara State University of Economics, 2020. http://dx.doi.org/10.46554/russian.science-2020.03-2-549/551.
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Stephens, R. R., et R. A. McFarlane. « Diode pumped upconversion laser with 100 mW output ». Dans OSA Annual Meeting. Washington, D.C. : Optica Publishing Group, 1992. http://dx.doi.org/10.1364/oam.1992.mj3.
Texte intégralRésumé :
An upconversion laser pumped at 797 nm has produced 100 mW output at 551 nm with an overall IR to visible conversion efficiency of more than 5%. A high power, narrow band, multi-element semiconductor diode laser system was used to longitudinally pump the upconversion laser crystal in a manner that provided an efficient matching of laser and pump mode geometries and a spectral linewidth that closely matched the absorption width of the active rare earth ion at the operating temperature. The maximum pump power delivered to the upconversion crystal was 1.75 W. The monolithic laser crystal was a 5 mm long cylinder of Er5%:YLiF4 with dielectric reflectors applied to each end, and was cooled to 48 K. The absorbed pump power was 88% of the incident pump power. The system oscillated on two components of the 4S3/2-4I15/2 transition, at 550.97 nm (air) and 551.25 nm (air). A net IR-to-visible conversion efficiency of 5% was achieved. At the higher powers a slope efficiency of 8% has been demonstrated. Higher output power, improved efficiency, and better beam quality can be achieved with a better mode-match and an improved resonator design.
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Lenth, Wilfried, et Roger M. Macfarlane. « Infrared-pumped green and blue upconversion lasers ». Dans OSA Annual Meeting. Washington, D.C. : Optica Publishing Group, 1991. http://dx.doi.org/10.1364/oam.1991.thw1.
Texte intégralRésumé :
Upconversion lasers operate at wavelengths that are shorter than those used for pumping. Efficient upconversion lasing has been achieved in rare earth-doped materials using several different ex citation processes such as sequential two-photon absorption, energy transfer upconversion and a so-called absorption avalanche mechanism; in the latter case, the pump photons are not resonant with absorption from the ground state.1 All these processes involve the use of metastable, intermediate levels which act as a storage reservoir for pump energy. Following the demonstration of the first cw-pumped upconversion laser in 1986, we have achieved upconversion laser operation at violet, blue, green and red wavelengths in several fluoride host crystals doped with Nd3+, Ho3+, Er3+, and Tm3+ ions by pumping with cw dye, Ti:sapphire or diode lasers.1 These upconversion lasers operate at temperatures up to ~ 140 K using pump powers of a few hundred milliwatts. The use of longitudinal pumping of short, monolithic laser crystals resulted in fairly high pump intensities, which is important for these nonlinear excitation processes. Multistep upconversion excitation has been achieved in Er:YLiF4 by producing laser oscillation at 470 nm from the 2P3/2 level whose energy is more than three times higher than that of the 969-nm light used for pumping. At 77 K, green 551-nm laser output was obtained by pumping a 2-mm long Er:YLiF4 crystal with a 809-nm GaAl As diode laser. Recently, green and blue cw upconversion lasing at room temperature has been reported using fluorozirconate fibers doped with Ho3+ and Pr3+, respectively.2
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Filippchenkova, S. I. « PSYCHOLOGICAL VECTOR OF OVERCOMING PROFESSIONAL BURNOUT IN ONCOLOGISTS ». Dans The 16th «OCCUPATION and HEALTH» Russian National Congress with International Participation (OHRNC-2021). FSBSI “IRIOH”, 2021. http://dx.doi.org/10.31089/978-5-6042929-2-1-2021-1-548-551.
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Abstract: Oncologists are at high risk of developing professional burnout, which leads to a loss of individual and professional health, a decrease in the quality of medical services, medical errors, and interpersonal conflicts with colleagues and patients. Preservation of health in the professional activities of oncologists initiates the development of a system of psychological support for their professional activities, including psychological trainings, group and individual counseling in the context of the problems of medical practice. The aim of the study was to test the author's program for the correction of professional burnout in doctors. The study involved 45 oncologists from the Tver region. The psychodiagnostic toolkit of the study was made up by V.V. Boyko modified by E.P. Ilyin. Significant indicators of reduction of the leading symptoms of professional burnout among doctors were registered according to the results of testing carried out before and after the training. Conclusions of the study: the results of psychodiagnostic testing and approbation in medical practice confirm the effectiveness of the developed psychological training program in the prevention and correction of professional burnout of oncologists.
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Freitas, Luiza Isaia de. « INFLUÊNCIA DO ISOLAMENTO DOMICILIAR DEVIDO A PANDEMIA SOBRE A ROTINA ALIMENTAR DOS ANIMAIS MANTIDOS COMO PET NO BRASIL ». Dans II Congresso Brasileiro de Ciências Biológicas On-line. Revista Multidisciplinar de Educação e Meio Ambiente, 2021. http://dx.doi.org/10.51189/rema/1283.
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Introdução: Em março de 2020 a SARS-CoV-2 foi elevada ao status de pandemia. A fim de diminuir a disseminação viral, foi instituído o isolamento domiciliar sobre a população mundial. Tendo início dos casos na China, o Covid-19 distribuiu-se rapidamente pelo globo. Conforme estudos científicos há registros do vírus infectar cães, gatos e ferrets, todavia sem relatos de que se possa ocorrer a transmissão do patógeno presente nos pets aos humanos. Após o isolamento, foi possível observar o aumento de peso em parte da população, dado que conforme pesquisa também foi observado nos animais mantidos como pets no Brasil. Objetivo: Averiguar os impactos do isolamento domiciliar devido a pandemia da Covid-19 sobre a rotina alimentar de animais mantidos como pet no Brasil. Material e Métodos: Foi realizada pesquisa de caráter exploratório, de forma online, via formulário, obtendo 551 respostas de 22 estados e Distrito Federal. Resultados: As respostas obtidas na pesquisa foram referentes ao tipo de animal mantido como pet (cães, gatos, aves, répteis, roedores e outros), mudanças na rotina alimentar e de atividades dos pets anterior e após o isolamento domiciliar, sendo questionado sobre a observação ou não de aumento no escore corporal dos animais. Os dados obtidos após a análise foram que 30% dos pets desenvolveram sobrepeso após a pandemia, podendo relacionar os dados como resultado de maior fornecimento de alimento aos animais, tanto em periodicidade tanto em quantidade em associação a menor quantidade de atividades físicas realizadas com os animais, como atividades de recreação e passeios. Conclusão: Através da análise dos dados, foi constatado que assim como em humanos, percentual dos animais mantidos como pet no Brasil também adquiriram sobrepeso após o isolamento domiciliar. Sendo dado que 30% destes após a pandemia tiveram aumento em seu escore corporal, fato ligado ao maior fornecimento de alimento aos animais pelos tutores, com maior fornecimento de petiscos, gerando uma superalimentação dos pets a qual em conjunto com o menor índice de atividade física realizada com os animais, como a menor periodicidade de passeios e atividades de recreação, levaram ao sobrepeso dos animais mantidos como pet no Brasil.
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Wright, Albion D., Brandon S. Willis, Anna Gomez, Mark L. Boys, Robert K. DeLisle, Laurence E. Burgess, Mark C. Munson et al. « Abstract 551 : A potent and selective cFMS inhibitor regulates the tumor macrophage microenvironment leading to tumor growth inhibition ». Dans Proceedings : AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011 ; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-551.
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Bremer, Claus. « Automatic Blade Repair System Based on Reverse Engineering Strategies ». Dans ASME 1998 International Gas Turbine and Aeroengine Congress and Exhibition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/98-gt-551.
Texte intégralRésumé :
The compressor and turbine blades of aircraft engines and gas turbines have to be overhauled at regular intervals. First, the worn out blades are welded manually or by a welding robot. After welding, the blades will normally be shaped by hand, using grinding bands. Automation of the shaping of the welded beads reduces costs and process time while giving higher accuracy and quality. The following repair technique has been found to allow automatic tooling of the weld on final domains of blades, via a chain of processes, which run on one, single standard, three axis machining center. 1) Digitization of blade cross sections below the welded bead; 2) Calculation of the nominal geometry of the final domains; 3) Calculation of the NC processing programs; 4) NC processing of the final domains of the blades. The complete repair for one blade (steps 1 to 4) takes two to three minutes. The 3D digitizing system captures the actual geometry and chucking position of the blades completely. Therefore, no CAD data or measuring data of a master piece are required and the free chucking position of the blades allows simple fixtures. The blades can be repaired without user interaction, individually or in a batch quantity.
Rapports d'organisations sur le sujet "551..2"
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Pavlovic, Noel, Barbara Plampin, Gayle Tonkovich et David Hamilla. Special flora and vegetation of Indiana Dunes National Park. National Park Service, 2024. http://dx.doi.org/10.36967/2302417.
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The Indiana Dunes (comprised of 15 geographic units (see Figure 1) which include Indiana Dunes National Park, Dunes State Park, and adjacent Shirley Heinze Land Trust properties) are remarkable in the Midwest and Great Lakes region for the vascular plant diversity, with an astounding 1,212 native plant species in an area of approximately 16,000 acres! This high plant diversity is the result of the interactions among postglacial migrations, the variety of soil substrates, moisture conditions, topography, successional gradients, ?re regimes, proximity to Lake Michigan, and light levels. This richness is all the more signi?cant given the past human alterations of the landscape resulting from logging; conversion to agriculture; construction of transportation corridors, industrial sites, and residential communities; ?re suppression; land abandonment; and exotic species invasions. Despite these impacts, multiple natural areas supporting native vegetation persist. Thus, each of the 15 units of the Indiana Dunes presents up to eight subunits varying in human disturbance and consequently in ?oristic richness. Of the most signi?cant units of the park in terms of number of native species, Cowles Dunes and the Dunes State Park stand out from all the other units, with 786 and 686 native species, respectively. The next highest ranked units for numbers of native species include Keiser (630), Furnessville (574), Miller Woods (551), and Hoosier Prairie (542). The unit with lowest plant richness is Heron Rookery (220), with increasing richness in progression from Calumet Prairie (320), Hobart Prairie Grove (368), to Pinhook Bog (380). Signi?cant natural areas, retaining native vegetation composition and structure, include Cowles Bog (Cowles Dunes Unit), Howes Prairie (Cowles Dunes), Dunes Nature Preserve (Dunes State Park), Dunes Prairie Nature Preserve (Dunes State Park), Pinhook Bog, Furnessville Woods (Furnessville), Miller Woods, Inland Marsh, and Mnoke Prairie (Bailly). Wilhelm (1990) recorded a total of 1,131 native plant species for the ?ora of the Indiana Dunes. This was similar to the 1,132 species recorded by the National Park Service (2014) for the Indiana Dunes. Based on the nomenclature of Swink and Wilhelm (1994), Indiana Dunes National Park has 1,206 native plant species. If we include native varieties and hybrids, the total increases to 1,244 taxa. Based on the nomenclature used for this report?the Flora of North America (FNA 2022), and the Integrated Taxonomic Information System (ITIS 2022)?Indiana Dunes National Park houses 1,206 native vascular plant species. As of this writing (2020), the Indiana Dunes is home to 37% of the species of conservation concern in Indiana (241 out of 624 Indiana-listed species): state extirpated = 10 species, state endangered = 75, and state threatened = 100. Thus, 4% of the state-listed species in the Indiana Dunes are extirpated, 31% endangered, and 41% threatened. Watch list and rare categories have been eliminated. Twenty-nine species once documented from the Indiana Dunes may be extirpated because they have not been seen since 2001. Eleven have not been seen since 1930 and 15 since 1978. If we exclude these species, then there would be a total of 1,183 species native to the Indiana Dunes. Many of these are cryptic in their life history or diminutive, and thus are di?cult to ?nd. Looking at the growth form of native plants, <1% (nine species) are clubmosses, 3% (37) are ferns, 8% (297) are grasses and sedges, 56% (682) are forbs or herbs, 1% (16) are herbaceous vines, <1% (7) are subshrubs (woody plants of herbaceous stature), 5% (60) are shrubs, 1% (11) are lianas (woody vines), and 8% (93) are trees. Of the 332 exotic species (species introduced from outside North America), 65% (219 species) are forbs such as garlic mustard (Alliaria petiolata), 15% (50 species) are graminoids such as phragmites (Phragmites australis ssp. australis), 2% (seven species) are vines such as ?eld bindweed (Convulvulus arvensis), <1% (two species) are subshrubs such as Japanese pachysandra (Pachysandra terminalis), 8% (28 species) are shrubs such as Asian bush honeysuckle (Lonicera spp.), 1% (three species) are lianas such as oriental bittersweet (Celastrus orbiculatus), and 8% (23 species) are trees such as tree of heaven (Ailanthus altissimus). Of the 85 adventive species, native species that have invaded from elsewhere in North America, 14% (11 species) are graminoids such as broom sedge (Andropogon virginicus), 57% (48 species) are forbs such as fall phlox (Phlox paniculata), 5% (six species) are shrubs such as Carolina allspice (Calycanthus floridus), 3% (two species) are subshrubs such as holly leaved barberry (Berberis repens), 1% (one species) is a liana (trumpet creeper (Campsis radicans), 3% two species) are herbaceous vines such as tall morning glory (Ipomoea purpurea), and 17% (15 species) are trees such as American holly (Ilex opaca). A total of 436 species were found to be ?special? based on political rankings (federal and state-listed threatened and endangered species), species with charismatic ?owers, and those that are locally rare.