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1

Ito, Makoto, Sumiaki Fukuda, Shohei Sakata, Hisayo Morinaga, and 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.

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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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2

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 (December 6, 2014): 4472. http://dx.doi.org/10.1182/blood.v124.21.4472.4472.

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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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3

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 (November 15, 2013): 1810. http://dx.doi.org/10.1182/blood.v122.21.1810.1810.

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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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4

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 (November 16, 2012): 3677. http://dx.doi.org/10.1182/blood.v120.21.3677.3677.

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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 (December 6, 2014): 1756. http://dx.doi.org/10.1182/blood.v124.21.1756.1756.

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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 (May 20, 2013): 7045. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.7045.

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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, and M. Brunori. "Cytochrome c-551 and azurin oxidation catalysed by Pseudomonas aeruginosa cytochrome oxidase. A steady-state kinetic study." Biochemical Journal 230, no. 3 (September 15, 1985): 797–805. http://dx.doi.org/10.1042/bj2300797.

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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 (December 6, 2014): 2198. http://dx.doi.org/10.1182/blood.v124.21.2198.2198.

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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, and 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 (February 15, 1997): 35–42. http://dx.doi.org/10.1042/bj3220035.

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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, and 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 (May 20, 2012): 8065. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.8065.

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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]
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Ejército del Pueblo (FARC-EP), Fuerzas Armadas Revolucionarias de Colombia,. "Estatuto das Fuerzas Armadas Revolucionarias de Colombia, Ejército del Pueblo (1978-2007)." InSURgência: revista de direitos e movimentos sociais 2, no. 1 (March 21, 2017): 540–51. http://dx.doi.org/10.26512/insurgncia.v2i1.19025.

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12

Marcillas, Isabel. "F. Carbó, C. Gregori & R. X. Rosselló, (eds.), «La ironia en les literatures occidentals des de l’inici de segle fins a 1939», 2016, Barcelona, PAM, 551 pp." Caplletra. Revista Internacional de Filologia, no. 64 (March 22, 2018): 271. http://dx.doi.org/10.7203/caplletra.64.11396.

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Ressenya sobre el llibre de F. Carbó, C. Gregori & R. X. Rosselló, (eds.), «La ironia en les literatures occidentals des de l’inici de segle fins a 1939», 2016, Barcelona, Publicacions de l’Abadia de Montserrat, 551 pp., ISBN: 978-84-9883-873-2.
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Kulli, V. R., and K. M. Niranjan. "On Minimally Nonouterplanarity of the Semi Total (Point) Graph of a Graph." Journal of Scientific Research 1, no. 3 (August 29, 2009): 551–57. http://dx.doi.org/10.3329/jsr.v1i3.2578.

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We present here characterizations of graphs whose semi total (point) graphs are outerplanar and k-minimally nonouterplanar (k = 1, 2 or 3).Keywords: Semi total (Point) graph; Minimally nonouterplanarity; Outerplanar; Block.© 2009 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.DOI: 10.3329/jsr.v1i3.2578 J. Sci. Res. 1 (3), 551-557 (2009)
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Takahashi, K., Takeyoshi Tanaka, and S. Kose. "An Evacuation Model For Use In Fire Safety Design Of Buildings." Fire Safety Science 2 (1989): 551–60. http://dx.doi.org/10.3801/iafss.fss.2-551.

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15

Huber, Lynn. "Transforming Scriptures: African American Women Writers and the Bible, by Katherine Clay Bassard." Relegere: Studies in Religion and Reception 1, no. 2 (2011): 438–42. http://dx.doi.org/10.11157/rsrr1-2-551.

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Al-Hamood, M. H., D. P. Gilmore, C. A. Wilson, P. Tuohy-Jones, S. Drummond, and C. Gopalan. "The role of the hypothalamic β-adrenergic system in controlling the LH rise in short-term castrated rats." Journal of Endocrinology 114, no. 2 (August 1987): 167–72. http://dx.doi.org/10.1677/joe.0.1140167.

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ABSTRACT Intraventricular infusions of adrenaline and various pharmacological agents acting on β-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 μl) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed β1- and β2-agonist), fenoterol (a β2-agonist) and atenolol (a β1-antagonist). In contrast, prenalterol (a β1-agonist) and (2RS,3RS)-3-isopropylamino-1-(7-methylindan-4-yloxy)butan-2-ol (ICI 118 551) (a selective β2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective β2-agonist), propranolol (a mixed β-antagonist) and metoprolol (a β1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118 551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118 551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a β2-stimulatory component and the suppression of a β1-inhibitory component. J. Endocr. (1987) 114, 167–172
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Valenta, Vladimír, Marie Vlková, Jiří Holubek, Jiřina Metyšová, and Miroslav Protiva. "Potential antidepressants: 10-Amino-2-chloro-10,11-dihydrodibenzo[b,f]thiepins." Collection of Czechoslovak Chemical Communications 54, no. 7 (1989): 1979–94. http://dx.doi.org/10.1135/cccc19891979.

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Reduction of N-(2-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)formamide with lithium aluminium hydride resulted in the methylamino compound IV. The dimethylamino compound V was obtained by methylation of 10-amino-2-chloro-10,11-dihydrodibenzo[b,f]thiepin with formic acid and aqueous formaldehyde. Substitution reactions of 2,10-dichloro-10,11-dihydrodibenzo[b,f]thiepin with a series of primary and secondary amines afforded the title compounds VI to XXVIII. The bases were transformed to salts and pharmacologically tested. Only the pyrrolidino compound IX (hydrogen succinate VÚFB-15 551) showed a clear pharmacological profile of a potential antidepressant.
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Aguirre, Henry, Patricio Viteri, Pamela León, Yerimar Mayía, Patricio Cobos, Mariuxi Mero, and Beatriz Pernía. "Fitotoxicidad del cadmio sobre la germinación y crecimiento inicial de variedades de maíz Ecuatorianas." Bioagro 34, no. 1 (December 29, 2021): 3–14. http://dx.doi.org/10.51372/bioagro341.1.

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El cadmio (Cd) es un contaminante que genera inhibición de la germinación y disminución en la productividad de los cultivos. En Ecuador se ha demostrado la contaminación por este metal en algunos suelos agrícolas. El objetivo de esta investigación fue medir los efectos del Cd sobre la germinación y el crecimiento de las variedades de maíz INIAP-101, INIAP-122, INIAP-151, INIAP H-551, INIAP H-553, INIAP-180 y una variedad Autóctona de la provincia de Manabí en Ecuador. Se expusieron semillas de estas variedades a 0, 0,25, 0,5, 1, 2, 4 y 8 mg∙L-1 de CdNO3 durante 8 días y se determinó el día de inicio y porcentaje de germinación, así como la longitud de la radícula y del hipocótilo. El efecto del metal se evaluó mediante el cálculo de los índices de tolerancia y de fitotoxicidad. El porcentaje de germinación disminuyó 37,5% en la variedad INIAP H-551, y levemente en la Autóctona en el nivel de 1 mg∙L-1 de Cd; las otras no se vieron afectadas. Según el índice de tolerancia, la variedad más tolerante fue la Autóctona y las menos tolerantes INIAP-101 e INIAP-122. El índice integral de fitotoxicidad mostró la toxicidad del Cd en el siguiente orden: INIAP-101, INIAP H-551, INIAP-122, INIAP H-553, INIAP-180, INIAP-151 y la menos afectada fue la Autóctona. Se recomienda a los agricultores analizar la concentración de cadmio en el suelo previo al cultivo, y dependiendo del grado de contaminación, evitar las variedades menos tolerantes.
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Shi, Qingyu, Dandan Yin, Renru Han, Yan Guo, Yonggui Zheng, Shi Wu, Yang Yang, Shirong Li, Rong Zhang, and Fupin Hu. "Emergence and Recovery of Ceftazidime-avibactam Resistance in blaKPC-33-Harboring Klebsiella pneumoniae Sequence Type 11 Isolates in China." Clinical Infectious Diseases 71, Supplement_4 (November 15, 2020): S436—S439. http://dx.doi.org/10.1093/cid/ciaa1521.

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Abstract This is the first report of ceftazidime–avibactam resistance caused by the blaKPC-33 mutation through the D179Y variant during the treatment of blaKPC-2-positive Klebsiella pneumoniae-related infections in China. The blaKPC-33-containing K. pneumoniae was susceptible to meropenem–vaborbactam, cefepime–zidebactam, tigecycline, and polymyxin B. The blaKPC-33 gene was located on a 77 551-bp transformable plasmid harboring qnrS1 and blaLAP-2. Detecting blaKPC-33-positive K. pneumoniae clinical strains is important for infection control.
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PARK, KWANG-SOON. "WARPED PRODUCTS IN RIEMANNIAN MANIFOLDS." Bulletin of the Australian Mathematical Society 90, no. 3 (September 9, 2014): 510–20. http://dx.doi.org/10.1017/s0004972714000549.

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AbstractIn this paper we prove two inequalities relating the warping function to various curvature terms, for warped products isometrically immersed in Riemannian manifolds. This extends work by B. Y. Chen [‘On isometric minimal immersions from warped products into real space forms’, Proc. Edinb. Math. Soc. (2) 45(3) (2002), 579–587 and ‘Warped products in real space forms’, Rocky Mountain J. Math.34(2) (2004), 551–563] for the case of immersions into space forms. Finally, we give an application where the target manifold is the Clifford torus.
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O’Leary, Karen A., Sonia de Pascual-Teresa, Paul W. Needs, Yong-Ping Bao, Nora M. O’Brien, and Gary Williamson. "Corrigendum to “Effect of flavonoids and Vitamin E on cyclooxygenase-2 (COX-2) transcription” [Mutat. Res. 551 (1–2) (July 2004) 245–254]." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 749, no. 1-2 (September 2013): 92. http://dx.doi.org/10.1016/j.mrfmmm.2013.08.007.

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22

Dhorajia, Alpesh M., and Manoj K. Keshari. "Corrigendum to “Projective modules over overrings of polynomial rings” [J. Algebra 323 (2) (2010) 551–559]." Journal of Algebra 366 (September 2012): 217. http://dx.doi.org/10.1016/j.jalgebra.2012.05.022.

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23

Rosenfeld, Ron G., Hung Pham, Youngman Oh, George Lamson, and Linda C. Giudice. "IDENTIFICATION OF INSULIN-UKE GROWTH FACTOR-BINDING PROTEIN-2 (IGF-BP-2) AND A LOW MOLECULAR WEIGHT IGF-BP IN HUMAN SEMINAL PLASMA." Journal of Clinical Endocrinology & Metabolism 70, no. 2 (February 1990): 551–53. http://dx.doi.org/10.1210/jcem-70-2-551.

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24

Holm, Terje H. "Revanche og neutralitet: 1648–1814.Dansk Udenrigspolitiks Historie Vol. 2(Copenhagen: Danmarks Nationalleksikon, 2002). 551 pp. ISBN 87-7789-089-2." Scandinavian Journal of History 28, no. 3-4 (December 2003): 288–90. http://dx.doi.org/10.1080/03468750310001138.

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25

H O B I R. "EVALUASI POTENSI PRODUKSI BUNGA YLANG-YLANG." Jurnal Penelitian Tanaman Industri 9, no. 2 (July 15, 2020): 70. http://dx.doi.org/10.21082/jlittri.v9n2.2003.70-73.

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<p>Tanaman ylang-ylang (Canangium odoratum f. genumea), merupakan tanaman penghasil minyak atsiri yang nilainya cukup tinggi. Evaluasi potensi produksi bunga bertujuan untuk mendapatkan individu- individu yang produksi bunganya linggi untuk diteliti lebih lanjut dalam mendapatkan pohon unggul sebagai sumber benih Penelilian dilakukan di Sukamulya lahun 2000-2002 pada areal petanaman 1 ha (± 200 pohon) Petanaman berumur 12-15 tahun Evaluasi dilakukan dalam 2 tahap. Pada lahap petama, evaluasi dilakukan secara visual. Pohon-pohon yang dipilih adalah pohon dengan penampilan baik dengan ciri-ciri morfologis khas ylang-ylang, yaitu berbatang lurus, percabangan terkulai, permukaan batang licin dan terdapat bekas cabang (scars). Dari sekitar 200 pohon (erpilih 15 pohon yang berpenampilan paling baik. Pada lahap kedua, ke 1 5 pohon tersebut diamati petumbuhan dan produksi bunganya selama tiga tahun berturut-turut Hasilnya menunjukkan bahwa petumbuhan yang meliputi lingkar batang dan jumlah cabang tidak berbeda antar pohon. Sebaliknya produksi bunga sangat beragam antar pohon. Rata-rata produksi selama liga tahun berkisar antara 652-12 551 g/ph/tahun. Berdasarkan produktivitas dan fluktuasi produksi antar musim telah tcrpilih lima pohon yang produksi bunganya paling tinggi, yaitu No. 2/143, 8/06, 12/64, 14'113, dan 15/16 dengan produksi masing-masing 7 177, 8 352; 7 177; 12 551, dan 12 398 g/ph.</p><p>Kata kunci : Canangium odoratum f. genumea, cvaluasi, potensi produksi</p><p> </p><p><strong>ABSTRACT </strong></p><p><strong>Evaluation of the potency offlower yield of Ylang-ylang</strong></p><p>Ylang-ylang (Canangium odoratum f genumea) is the essential oil producing crop, which has high economic value. An evaluation of yield potential was aimed al selecting high yielding individuals which arc futher selected lo produce outstanding individuals as seed source. The evaluation was conducted in Sukamulya (Sukabumi) from 2000-2002 on the area of I ha ((+ 200 trees) Ihe trees was 1 2-15 years old. The evaluation was performed in 2 stages In Ihe irst stage the evaluation was conducted visually and based on Ihe specific morphological characters of ylang-ylang, which has erect trunk, plain surface, drooping branches and showing scars on Ihe surface of the trunk. From about 200 trees, 15 trees were selected as showing ihe best performance. In the second stage, the 15 selected trees were evaluated for their growth performance, including trunk circumference, number of branches and yield of fresh flowers for 3 years. Result showed that the trunk circumferences and the number of branches were nol different among the trees On the other hand, the yield of flowers was greatly variable, cither between the trees or between seasons. The average yield of flower in 3 year observation ranged from 652 to 12 551 g-'trcc/ycar. Based on the productivity the highest yielding trees were No. 2/143, 8/06, 12/64, 14/113, and 15/16 with the yield of flowers 7 177, 8 352; 7 177; 12 551, and 12 398 g'tree/ycar respectively.</p><p>Key words : Canangium odoratum f. genumea. evaluation, yield potency<br /><br /></p>
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Cepeda Ávila, Katuska Isabel, Rosa Miriam Armijos Acosta, and Virginia Barzola Veliz. "Desafíos de la investigación en Ecuador." RECIMUNDO 2, no. 2 (March 21, 2018): 536–51. http://dx.doi.org/10.26820/recimundo/2.(2).2018.536-551.

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En este artículo se desarrollan algunas ideas en torno a los retos y desafíos que enfrenta la investigación en Ecuador, en el marco de la educación superior. Parte de un objetivo general, que es esbozar una visión transformadora de la educación superior y la investigación hacia la transformación universitaria en Ecuador, así como los desafíos actuales a los que se enfrenta la educación superior. Sus objetivos específicos pasan por una caracterización de la educación superior ecuatoriana en cuanto a investigación, para luego plantear algunas ideas para una transformación universitaria en el marco de la investigación. El trabajo se realizó a través del método hermenéutico-dialéctico, utilizando la investigación documental. Como resultado se plantean 4 líneas generales que representan los grandes retos y desafíos a enfrentar en el nuevo contexto de la educación superior para potenciar la investigación en Ecuador.
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Issalys, Pierre. "JEAN-PHILIPPE COLSON, Droit public économique, 3éd., Paris, LGDJ, 2001, 551 p., ISBN 2-275-01949-9." Les Cahiers de droit 42, no. 4 (2001): 1166. http://dx.doi.org/10.7202/043692ar.

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28

Nowacki, Artur. "Odpowiedzialność nabywcy przedsiębiorstwa upadłego za zobowiązania związane z jego prowadzeniem." Gdańskie Studia Prawnicze, no. 2(54)/2022 (July 11, 2022): 54–62. http://dx.doi.org/10.26881/gsp.2022.2.05.

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Przedmiotem artykułu jest przede wszystko obrona stanowiska, zgodnie z którym art. 551 k.c., wprowadzający odpowiedzialność nabywcy przedsiębiorstwa za zobowiązania zbywcy związane z jego prowadzeniem, znajdzie w kontekście upadłości zastosowanie tylko do tych zobowiązań związanych z prowadzeniem przedsiębiorstwa, które stanowią zobowiązania masy upadłości, podczas gdy ze względu na art. 317 § 2 zdanie drugie pr. upadł. jego stosowanie jest wyłączone w odniesieniu do tych zobowiązań związanych z prowadzeniem przedsiębiorstwa, które stanowią zobowiązania upadłego. Tak samo będzie z zobowiązaniami ze stosunków pracy w konsekwencji jedynie odpowiedniego z mocy art. 317 ust. 2a pr. upadł. stosowania art. 231 k.p.
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Rappaport, Harry Z., Shlomi Constantini, Tali Sigal, and Lucia Shuger. "Intramedullary Fibrosarcoma of the Cervicomedullary Junction: A Case Report." Neurosurgery 21, no. 4 (October 1, 1987): 551–53. http://dx.doi.org/10.1227/00006123-198710000-00019.

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Abstract A 17-year-old girl presented with signs of increased intracranial pressure. On computed tomography, an enhancing intraaxial lesion in the region of the foramen magnum was demonstrated. Surgical excision was performed. The pathological diagnosis was low grade fibrosarcoma. Her subsequent course was complicated by cerebrospinal fluid seeding, a posterior fossa recurrence, and repeated subarachnoid hemorrhage with cerebral vasospasm. A combination of radiotherapy and intraventricular chemotherapy has left the patient symptom-free 2 years after operation. The intramedullary appearance of fibrosarcoma and the unusual subsequent clinical course are discussed. (Neurosurgery 21:551-553, 1987)
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Sazali, E. S., Md Rahim Sahar, and Sib Krishna Ghoshal. "Gold Nanoparticles Embedded Erbium-Lead-Tellurite Glass: Bonding Parameters Evaluation." Solid State Phenomena 268 (October 2017): 97–101. http://dx.doi.org/10.4028/www.scientific.net/ssp.268.97.

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Au NPs contents dependent modifications in the absorption and bonding parameters are inspected. Glass systems with composition (79-y)TeO2 – 15PbO – 5PbCl2 – 1Er2O3 – (y)AuCl3 where 0.0 ≤ y ≤ 0.1 mol% are prepared and characterized using X-ray Diffraction (XRD). The absorption characteristics of the glass are observed using UV-Visible-NIR (UV-VIS-NIR) spectrophotometer. XRD spectra confirm the amorphous nature of all samples. UV-VIS-NIR spectra reveal seven absorption bands centered at about 490, 526, 551, 652, 800, 982 and 1520 nm originating from 4I15/2 to 4F7/2, 2H11/2, 4S3/2,4F9/2, 4I9/2, 4I11/2 and 4I13/2 transitions, respectively. The low value of indicated an increase in the covalency and the positive sign of for all glass systems indicates the bonding between the RE ions and the surrounding ligand is covalent in nature.
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31

Schäfer, Imke K., Verena Lanny, Jörg Franke, Timothy I. Eglinton, Michael Zech, Barbora Vysloužilová, and Roland Zech. "Leaf waxes in litter and topsoils along a European transect." SOIL 2, no. 4 (October 25, 2016): 551–64. http://dx.doi.org/10.5194/soil-2-551-2016.

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Abstract. Lipid biomarkers are increasingly used to reconstruct past environmental and climate conditions. Leaf-wax-derived long-chain n-alkanes and n-alkanoic acids may have great potential for reconstructing past changes in vegetation, but the factors that affect the leaf wax distribution in fresh plant material, as well as in soils and sediments, are not yet fully understood and need further research. We systematically investigated the influence of vegetation and soil depth on leaf waxes in litter and topsoils along a European transect. The deciduous forest sites are often dominated by the n-C27 alkane and n-C28 alkanoic acid. Conifers produce few n-alkanes but show high abundances of the C24 n-alkanoic acid. Grasslands are characterized by relatively high amounts of C31 and C33 n-alkanes and C32 and C34 n-alkanoic acids. Chain length ratios thus may allow for distinguishing between different vegetation types, but caution must be exercised given the large species-specific variability in chain length patterns. An updated endmember model with the new n-alkane ratio (n-C31 + n-C33) / (n-C27 + n-C31 + n-C33) is provided to illustrate, and tentatively account for, degradation effects on n-alkanes.
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Warrach-Sagi, K., and V. Wulfmeyer. "Streamflow data assimilation for soil moisture analysis." Geoscientific Model Development Discussions 2, no. 1 (June 12, 2009): 551–79. http://dx.doi.org/10.5194/gmdd-2-551-2009.

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Abstract. Streamflow depends on the soil moisture of a river catchment and can be measured with relatively high accuracy. The soil moisture in the root zone influences the latent heat flux and hence the quantity and spatial distribution of atmospheric water vapour and precipitation. As numerical weather forecast and climate models require a proper soil moisture initialization for their land surface models, we enhanced an Ensemble Kalman Filter to assimilate streamflow timeseries into the multi-layer land surface model TERRA-ML of the regional weather forecast model COSMO. The impact of streamflow assimilation was studied by an observing system simulation experiment in the Enz River catchment (located at the downwind side of the northern Black Forest in Germany). The results demonstrate a clear improvement of the soil moisture field in the catchment. We illustrate the potential of streamflow data assimilation for weather forecasting and discuss its spatial and temporal requirements for a corresponding, automated river gauging network.
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Schuiling, R. D., and P. L. de Boer. "Rolling stones; fast weathering of olivine in shallow seas for cost-effective CO<sub>2</sub> capture and mitigation of global warming and ocean acidification." Earth System Dynamics Discussions 2, no. 2 (December 6, 2011): 551–68. http://dx.doi.org/10.5194/esdd-2-551-2011.

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Abstract. Human CO2 emissions may drive the Earth into a next greenhouse state. They can be mitigated by accelerating weathering of natural rock under the uptake of CO2. We disprove the paradigm that olivine weathering in nature would be a slow process, and show that it is not needed to mill olivine to very fine, 10 μm-size grains in order to arrive at a complete dissolution within 1–2 year. In high-energy shallow marine environments olivine grains and reaction products on the grain surfaces, that otherwise would greatly retard the reaction, are abraded so that the chemical reaction is much accelerated. When kept in motion even large olivine grains rubbing and bumping against each other quickly produce fine clay- and silt-sized olivine particles that show a fast chemical reaction. Spreading of olivine in the world's 2% most energetic shelf seas can compensate a year's global CO2 emissions and counteract ocean acidification against a price well below that of carbon credits.
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Lee, Kyoung, Hak Kim, Hee Shin, and Joo Cha. "Stereotactic biopsy of the breast using a decubitus table: comparison of histologic underestimation rates between 11- and 8-gauge vacuum-assisted breast biopsy." SpringerPlus 2, no. 1 (2013): 551. http://dx.doi.org/10.1186/2193-1801-2-551.

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Leblanc, K., B. Quéguiner, P. Raimbault, and N. Garcia. "Efficiency of the silicate pump at a coastal oligotrophic site in the Mediterranean Sea." Biogeosciences Discussions 2, no. 3 (May 9, 2005): 551–80. http://dx.doi.org/10.5194/bgd-2-551-2005.

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Abstract. A one-year survey of the sedimenting particulate material was conducted at the SOFi site located on the edge of the continental slope in the Gulf of Lions (Northwestern Mediterranean) between September 1999 and December 2000. The main focus of this paper was to investigate the seasonal pattern of particulate biogenic silica (BSi) sedimentation fluxes in comparison with the particulate carbon fluxes and establish annual budgets of Si and C export. The pattern of the downward flux of BSi was partly typical with increased daily sedimentation rates during spring followed by smaller peaks during summer. However, an unusual sedimentation event was recorded in the bottom trap in February before the spring thermal stratification occurred, and represented 37% of the annual BSi mass flux. The total annual BSi flux at the SOFi site was estimated from the bottom trap and amounted to 86.8 mmol Si m-2 y-1, while the organic carbon flux amounted to 154.9 mmol C m-2 y-1. The overall efficiency of C export to depth compared to surface primary production budgets was low (3%) and similar to values found for oligotrophic regions of the Eastern Mediterranean. On the other hand, we documented a very high efficiency of the Si export at the SOFi site, with 62% of the Si produced in the surface layer exported to the bottom trap. The excellent correlation between BSi and particulate organic C (POC) in the bottom trap further indicates that the bulk of the organic matter is transferred to depth in association with diatoms. However, the main fraction of the C produced by phytoplankton is lost in the water column through oxidation or metabolisation, while biogenic silica is more efficiently transferred to depth. This strong Si/C decoupling with depth is likely to be the cause of the spring depletion of silicic acid over the entire water column which was observed by mid-April in a companion study (Leblanc et al., 2003) and may cause a severe Si limitation of the diatom spring bloom in this oligotrophic region of the Gulf of Lions.
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Song, B., N. J. Palleroni, and M. M. Häggblom. "Description of strain 3CB-1, a genomovar of Thauera aromatica, capable of degrading 3-chlorobenzoate coupled to nitrate reduction." International Journal of Systematic and Evolutionary Microbiology 50, no. 2 (March 1, 2000): 551–58. http://dx.doi.org/10.1099/00207713-50-2-551.

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37

Kiang, P. N. c. "Pedagogies of Life and Death: Transforming Immigrant/Refugee Students and Asian American Studies." positions: east asia cultures critique 5, no. 2 (September 1, 1997): 551–77. http://dx.doi.org/10.1215/10679847-5-2-551.

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38

Avila, C., S. Karwowska, C. Lai, and T. Evans. "551 TELBIVUDINE SHOWS NO ACTIVITY AGAINST 8 DIFFERENT CLINICAL HIV ISOLATES AND 2 MULTI-DRUG RESISTANT HIV ISOLATES." Journal of Hepatology 50 (April 2009): S204. http://dx.doi.org/10.1016/s0168-8278(09)60553-5.

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Bonilla Medina, Paola Sophia, Christian Leonel Breuillet Barrera, and Juan Rafael Guerrero Manueles. "Caracterización clínico epidemiológica de las cardiopatías congénitas en niños. Instituto Hondureño de Seguridad Social." Acta Pediátrica Hondureña 6, no. 1 (October 7, 2016): 415–20. http://dx.doi.org/10.5377/pediatrica.v6i1.2902.

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Antecedentes: Las malformaciones congénitas que más frecuentemente determinan malformaciones infantiles son las cardiopatías, producen 30% de las muertes en pacientes pediátricos. Desde que en 1939 Robert Gross realizó la primera intervención quirúrgica de un paciente con cardiopatía congénita (CC), éstas han cobrado gran importancia para la medicina y la salud pública.Objetivo: del estudio fue caracterizar clínica y epidemiológicamente los pacientes que presentaron cardiopatías congénitas en la consulta externa de cardiología del Hospital Regional del Norte- Instituto Hondureño de Seguridad Social (HRNIHSS) durante el período de enero a octubre del 2015.Pacientes y Métodos: Se realizó un estudio de enfoque cuantitativo, descriptivo transversal en la consulta externa HRN-IHSS, la población fue de 859 pacientes atendidos y la muestra 551 pacientes en quienes se confirmó la presencia de cardiopatía. Los datos se obtuvieron de los informes de atenciones diarias entre los meses de enero a octubre del 2015.Resultados: Se obtuvieron 551 pacientes con cardiopatías congénitas. 294 (53.35%) de los pacientes eran del género masculino y 257 (46.65%) del género femenino. 265(48.1%) estaban en edades comprendidas entre 1-2 años. 191 (34.66%) de los niños tenían comunicación interauricular (CIA).Conclusiones: El género masculino y los lactantes fueron los más afectados por cardiopatías congénitas.Acta Pediátrica Hondureña, Vol. 6, No. 1 Abril 2015 a Septiembre 2015: 415-420
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40

Varios, Autores. "Recensiones." MHNH. Revista Internacional de Investigación sobre Magia y Astrología Antiguas, no. 14 (December 1, 2014): 293–318. http://dx.doi.org/10.24310/mhnh.vi14.15656.

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Wolfgang Hübner, Manilius, Astronomica, Buch V, Bd. 1 Einführung, Text und Übersetzung, S. 304 + Farbtafeln; Bd. 2 Kommentar, S. 450, ‘Sammlung wissenschaftlicher Commentare’ Berlin – New York, Walter de Gruyter, 2010 (Carlo Santini)György Németh, Supplementum Audollentianum, Hungarian Polis Studies, 20, Zaragoza-Budapest-Debrecen, 2013, 239 pp. (Clelia Martínez Maza).Sabino Perea Yébenes, Officium Magicum. Estudios de magia, teúrgia, necromancia, supersticiones, milagros y demonología en el mundo greco-romano (Thema Mundi 6), Madrid-Salamanca, Signifer Libros, 2014, 551 pp. (Santiago Montero).Miguel Requena Jiménez, Omina mortis. Presagios de muerte. Cuando los dioses abandonan al emperador romano, Madrid, Abada Editores, 2014, 328 pp. (Fco. Javier Fernández Nieto).
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41

Little, Todd D., Mara Brendgen, Brigitte Wanner, and Lothar Krappmann. "Children’s Reciprocal Perceptions of Friendship Quality in the Sociocultural Contexts of East and West Berlin." International Journal of Behavioral Development 23, no. 1 (March 1999): 63–89. http://dx.doi.org/10.1080/016502599384008.

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Testing 551 East and 210 West Berlin children (grades 2-5), we sought to: (1) gain a broader understanding of the reciprocal nature of children’s friendships, especially their perceptions of friendship quality; and (2) examine sociocultural influences on such perceptions. We expected friends’ perceptions to form two distinct types of perceptions: (i) objectively perceived and, thus, shared interpersonal perceptions; and (ii) subjectively interpreted and, thus, nonshared intrapersonal perceptions. Mean and covariances structures analyses revealed that: (a) our distinction was well supported and generalisable across both contexts; and (b) East Berlin children reported more perceived friendship conflict, fewer mutual visits and sleep-overs, and less fun in their play activities than did their West Berlin age-mates. These differences are consistent with known characteristics of these two distinct sociocultural contexts.
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42

Kantarjian, Hagop M., Richard A. Larson, Francois Guilhot, Stephen G. O’Brien, and Brian J. Druker. "Declining Rates of Adverse Events (AEs), Rare Occurrence of Serious AEs (SAEs), and No Unexpected Long-Term Side Effects at 5 Years in Patients with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP) Initially Treated with Imatinib (IM) in the International Randomized Study of Interferon vs STI571 (IRIS)." Blood 108, no. 11 (November 1, 2006): 2136. http://dx.doi.org/10.1182/blood.v108.11.2136.2136.

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Abstract The IRIS trial compared interferon alfa + cytarabine (IFN+Ara-C) and imatinib (IM) in patients (pts) with newly diagnosed CML-CP. Among 553 pts randomized to receive 400 mg IM, 157 (28%) discontinued for reasons which included AEs or deaths unrelated to CML and treatment (6%) and unsatisfactory therapeutic effect (11%). Only 2.4% discontinued due to drug-related AEs. The average daily dose was 389±71 mg, suggesting that no major dose modifications were required due to toxicity. In pts still on IM, the average doses was 382±50 mg. Average duration of exposure is 50 mos (median 60 mos). Table 1 summarizes the most frequently reported non-hematologic AEs (regardless of relationship to study drug) in pts who started IM therapy and those who were still on IM at 2 and 4 years (n=456 and 409 respectively). Table 1. AEs (≥ 20%) on First-Line Imatinib Therapy AE All grades N= 551 (%) All grades, after 2 yrs N = 456 (%) All grades, after 4 yrs N = 409 (%) Grades 3/4 N= 551 (%) Fluid retention 61.7 20.2 5.6 2.5 – Superficial edema 59.9 18.2 5.1 1.5 – Other fluid retention events 6.9 2.4 0.7 1.3 Nausea 49.5 15.4 3.4 1.3 Muscle cramps 49.2 22.8 7.3 2.2 Musculoskeletal pain 47.0 20.8 6.1 5.4 Diarrhea 45.4 23.0 5.1 3.3 Rash and related terms 40.1 13.8 2.4 2.9 Fatigue 38.8 11.4 2.9 1.8 Headache 37.0 12.1 3.4 0.5 Abdominal pain 36.5 15.4 3.4 4.2 Joint pain 31.4 9.2 2.0 2.5 Nasopharyngitis 30.5 14.3 3.7 0 Hemorrhage 28.9 14.3 5.1 1.8 Myalgia 24.1 4.6 1.5 1.5 Vomiting 22.5 9.2 3.7 2.0 Upper respiratory tract infection 21.2 11.2 2.7 0.2 Cough 20.0 7.7 3.4 0.2 Hematologic toxicities were the most frequently occurring grade 3/4 AEs (Table 2). Table 2. Grade 3/4 laboratory abnormalities on First-line Imatinib Overall N = 551 (%) After 2 years N= 456 (%) After 4 years N= 409 (%) Hematologic – Neutropenia 16.7 7 1.0 – Thrombocytopenia 8.9 1.5 0.2 – Anemia 4.4 1.8 0.5 Biochemical – ↑ SGOT/SGPT 5.3 0.4 0 – ↑Total bilirubin 1.1 0.4 0.2 The most frequent reported AEs as well as grade 3/4 hematological and biochemical toxicities were observed at decreasing frequencies throughout therapy. After 4 years, 8% of pts experienced an SAE, compared with 14%, 12%, 7.5%, and 9% during year one through four of therapy. Overall, only 6% of pts had SAEs considered related to study drug (1.5% pts after 4 years of IM). Congestive heart failure/cardiac dysfunction (incl. pulmonary edemas) were reported for 3% of pts (<1% grade 3/4) and pleural effusion in 1% (<1% grade 3/4). Despite much shorter average exposure (12 mos), similar % of these AEs were noted for IFN+Ara-C. Although it should be considered that pts more likely to experience grade 3/4 events may have discontinued from the study prematurely, the 5-year data with IM in pts with newly diagnosed CML-CP show declining frequencies of AEs and SAEs over time. Occurrence of SAEs and laboratory abnormalities with long-term follow-up was rare. No unexpected long-term side effects were noted. These results confirm the IM tolerability and safety profile for durations exceeding 4 years.
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Nelemans, Stefanie A., Wim H. J. Meeus, Susan J. T. Branje, Karla Van Leeuwen, Hilde Colpin, Karine Verschueren, and Luc Goossens. "Social Anxiety Scale for Adolescents (SAS-A) Short Form: Longitudinal Measurement Invariance in Two Community Samples of Youth." Assessment 26, no. 2 (January 4, 2017): 235–48. http://dx.doi.org/10.1177/1073191116685808.

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In this study, we examined the longitudinal measurement invariance of a 12-item short version of the Social Anxiety Scale for Adolescents (SAS-A) in two 4-year longitudinal community samples ( Nsample 1 = 815, Mage T1 = 13.38 years; Nsample 2 = 551, Mage T1 = 14.82 years). Using confirmatory factor analyses, we found strict longitudinal measurement invariance for the three-factor structure of the SAS-A across adolescence, across samples, and across gender. Some developmental changes in social anxiety were found from early to mid-adolescence, as well as gender differences across adolescence. These findings suggest that the short version of the SAS-A is a developmentally appropriate instrument that can be used effectively to examine adolescent social anxiety development.
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44

Sadananda, Ranjitha C., Aswathi M. Menon, Sujatha Rathod, Anuradha Appaji, and Harish B. Hanumantharayappa. "Assessment of visual disability, clinical and demographic profile from Unique Disability Identification Details (UDID) card applicants in Regional Institute of Ophthalmology (RIO) in South India." IP International Journal of Ocular Oncology and Oculoplasty 8, no. 1 (May 15, 2022): 46–51. http://dx.doi.org/10.18231/j.ijooo.2022.010.

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To ascertain the degree and causes of visual disability, clinical and demographic data of UDID card applicants at RIO MOH Karnataka South India.It is a cross-sectional observation study, data collected from the UDID PORTAL where applicants applied between July 2019 to March 2020. Totally 551 applicants details were collected. Degree of visual disability and its causes, demographic details like age, gender, education, marital and employment status, annual income along with that other clinical details were ascertained. Among the 551 applications, 368 were men and 183 were women highlighting a significant gender bias. Almost 2/3 of applications were in the age group 20 to 50. 60% of applicants were married. 95% of applicants were in the blind category while only 4.3% were certified as having low vision. 47% of applicants were BPL Card holders and were dependent on the family member for livelihood. 47% of the applicants had completed basic education (10 std/SSLC). Retinitis pigmentosa was the top cause of blindness. Retinal pathologies constitute the leading cause among them majority had Retinitis pigmentosa. Genetic counseling plays a significant proactive role in the prevention of the disease. Creating awareness among employers to provide adequate protective equipment could help in reducing the disease burden of phthisis bulbi. Government and NGOs should prepare appropriate plans and implement them to rehabilitate individuals with visual disabilities. There is a need to create better awareness about the benefits of UDID CARDS in the community in general and among people with blindness and low vision in particular.
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45

Visser, Frank, Valeria Valsecchi, Lucio Annunziato, and Jonathan Lytton. "Analysis of Ion Interactions with the K+ -dependent Na+/Ca+ Exchangers NCKX2, NCKX3, and NCKX4." Journal of Biological Chemistry 282, no. 7 (December 15, 2006): 4453–62. http://dx.doi.org/10.1074/jbc.m610582200.

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K+-dependent Na+/Ca2+ exchangers (NCKX) catalyze cytosolic Ca2+ extrusion and are particularly important for neuronal Ca2+ signaling. Of the five mammalian isoforms, the detailed functional characteristics have only been reported for NCKX1 and -2. In the current study, the functional characteristics of recombinant NCKX3 and -4 expressed in HEK293 cells were determined and compared with those of NCKX2. Although the apparent affinities of the three isoforms for Ca2+ and Na+ were similar, NCKX3 and -4 displayed ∼40-fold higher affinities for K+ ions than NCKX2. Functional analysis of various NCKX2 mutants revealed that mutation of Thr-551 to Ala, the corresponding residue in NCKX4, resulted in an apparent K+ affinity shift to one similar to that of NCKX4 without a parallel shift in apparent Ca2+ affinity. In the converse situation, when Gln-476 of NCKX4 was converted to Lys, the corresponding residue in NCKX2, both the K+ and Ca2+ affinities were reduced. These results indicate that the apparently low K+ affinity of NCKX2 requires a Thr residue at position 551 that may reduce the conformational flexibility and/or K+ liganding strength of side-chain moieties on critical neighboring residues. This interaction appears to be specific to the structural context of the NCKX2 K+ binding pocket, because it was not possible to recreate the K+-specific low affinity phenotype with reciprocal mutations in NCKX4. The results of this study provide important information about the structure and function of NCKX proteins and will be critical to understanding their roles in neuronal Ca2+ signaling.
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Alvarenga, Renata Oliveira, Julio Marcos-Filho, and Tathiana Silva Timóteo. "Assessment of the physiological potential of super sweet corn seeds." Journal of Seed Science 35, no. 3 (2013): 340–46. http://dx.doi.org/10.1590/s2317-15372013000300010.

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The assessment of physiological potential is essential in seed quality control programs. This study compared the sensitivity of different procedures for evaluating super sweet corn seed vigor, focusing on the primary root protrusion test. Six seed lots, each of the SWB 551 and SWB 585 hybrids, were used. Seed physiological potential was evaluated by germination and vigor tests (speed of germination, traditional and saturated salt accelerated aging, cold test, seedling length, seedling emergence and primary root protrusion). Primary root protrusion was evaluated every 12 hours at 15 °C, 20 °C and 25 °C using two criteria (primary root protrusion and seedlings at the 2 mm root stage). It was concluded that the primary root protrusion test at 15 °C can evaluate super sweet corn seed vigor by counting the number of seedlings at the 2 mm root stage.
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Dupont, Jean-Claude. "REFORD, ALEXANDER. Des jardins oubliés, 1860-1960. Québec, Les Publications du Québec, 2000, 209 p. ISBN 2-551-18097-X." Rabaska: Revue d'ethnologie de l'Amérique française, no. 1 (2003): 197. http://dx.doi.org/10.7202/201630ar.

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48

LUDWIG, ALEXANDER. "IGNAZ PLEYEL (1757–1831) PRUSSIAN QUARTETS 4–6 Pleyel Quartett Köln cpo 777 551–2, 2012; one disc, 59 minutes." Eighteenth Century Music 11, no. 1 (February 3, 2014): 137–39. http://dx.doi.org/10.1017/s1478570613000535.

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49

Hempt, Claudia, Jean-Pierre Kaiser, Olivier Scholder, Tina Buerki-Thurnherr, Heinrich Hofmann, Alexandra Rippl, Tobias B. Schuster, Peter Wick, and Cordula Hirsch. "The impact of synthetic amorphous silica (E 551) on differentiated Caco-2 cells, a model for the human intestinal epithelium." Toxicology in Vitro 67 (September 2020): 104903. http://dx.doi.org/10.1016/j.tiv.2020.104903.

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50

Zhang, Jin, Zengzhe Xi, Xinzhe Wang, Hao Feng, Wei Long, and Aiguo He. "Ferroelectric Properties and Spectroscopic Characterization of Pb(Mg1/3Nb2/3)O3-32PbTiO3:Er3+/Sc3+ Crystal." Crystals 11, no. 10 (September 23, 2021): 1155. http://dx.doi.org/10.3390/cryst11101155.

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An Er3+/Sc3+ co-doped 0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3 ferroelectric single crystal was grown by high-temperature flux method. The remnant polarization Pr is 27.97 µC/cm2 and the coercive field Ec is 8.26 kV/cm for [100] oriented crystal. Green (524 and 551 nm) and red (654 nm) emission bands are generated at the 980 nm excitation, which corresponds to the 2H11/2→ 4I15/2, 4S3/2→ 4I15/2 and 4F9/2→ 4I15/2 transitions of Er3+, respectively. Judd–Ofelt theory has been applied to predict the spectroscopic characteristics of the as-grown crystals. The obtained J–O intensity parameters Ωt (t = 2, 4 and 6) are Ω2 = 0.76 × 10−20 cm2, Ω4 = 1.0 × 10−20 cm2, Ω6 = 0.55 × 10−20 cm2. Spectroscopic characteristics, including optical transition probabilities, branching ratio, and radiative lifetime of Er3+ in the crystal, are determined. The calculated radiative lifetimes of 4I13/2 and 4I11/2 energy levels are 2.82 ms and 2.61 ms, respectively. These investigations provide possibilities for the crystal Pb(Mg1/3Nb2/3)O3-0.32PbTiO3:Er3+/Sc3+ to be a new type of multifunctional crystal integrating electricity-luminescence.
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