324 research outputs found

    Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

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    Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective: To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2–5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results: The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion: CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT01201837

    Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

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    Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT0120183

    292. Towards Large-Scale Manufacturing of Adeno-Associated Virus by Transient Transfection of HEK293 Suspension Cells in a Stirred Tank Bioreactor Using Serum-Free Medium

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    Adeno-Associated Virus (AAV) vectors showing safety profile in phase I clinical trials and its ability to transduce gene expression in various tissues have made it a vector of choice for gene delivery. There are different modes of AAV vector production and each has advantages and disadvantages. Here we demonstrated that the production of AAV by transient transfection in a serum-free medium using NRC's patented cGMP compliant human embryonic kidney HEK293 cell line (clone HEK293SF-3F6) adapted for growth in suspension can be readily scaled-up in stirred tank bioreactors. We employed triple-plasmid / polyethylenimine (PEI) based transient transfection technique. As a proof of concept, we demonstrated that nine serotypes of AAV (AAV-1 to AAV-9) encoding GFP can be produced by our cell line HEK293SF with yields of about 1E+13 genome-containing particles per liter (Vg/L). Depending on the serotypes 4-30% of AAV is present in the supernatant of the cell culture at 48hpt. The presence of plasmids and plasmid polyplexes that were not taken up by the cells or were not brought into the cell nucleus were removed by Iodixanol-ultracentrifugation method and Benzonase treatment before analyzing by real-time PCR. About 25% loss in genome containing viral particle counts were observed by Iodixanol purification method based on infectivity assay. Productions of AAV2 and AAV6 encoding GFP were demonstrated in 3L stirred tank bioreactors. Purification scheme was based on column chromatography - a scalable process. Different chromatography media, such as cation exchanger, anion exchanger and hydrophobic interaction chromatography, were tested with each AAV serotypes for their ability to adsorb and elute efficiently. The purification scheme was then adopted by integrating best chromatography medium and sequence dependent upon the AAV serotype in use. We demonstrated the purification scheme for AAV2 based on ion-exchange and hydrophobic interaction chromatography steps. The SDS-PAGE showed the purity of the final product and the presence of three capsid proteins VP1, VP2 and VP3 on Western blot corresponding to the only three bands present in the final product on SDS-PAGE. To extend the storage life of AAV we explored lyophilization technique to study the stability of AAV2 and AAV6 under lyophilized conditions. The AAV2 and AAV6 were stable for over 40 weeks based on infectivity assay. We demonstrated the scalability of the process up to 45L. Productions tested in 20 and 500 mL cultures in shake flasks were scaled up in 2 and 45L cultures (in 3- and 60-L stirred tank bioreactors, respectively). The volumetric yields and purification recoveries were comparable at all of these production scale levels demonstrating scalability of transient transfection at even larger scale is possible to generate material necessary for dosages required for gene therapy application

    Socially Communicative Eye Contact and Gender Affect Memory

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    Because of their value as a socially communicative cue, researchers have strived to understand how the gaze of other people influences a variety of cognitive processes. Recent work in social attention suggests that the use of images of people in laboratory studies, as a substitute for real people, may not effectively test socially communicative aspects of eye gaze. As attention affects many other cognitive processes, it is likely that social attention between real individuals could also affect other cognitive processes, such as memory. However, from previous work alone, it is unclear whether, and if so how, socially communicative eye gaze affects memory. The present studies test the assumption that socially communicative aspects of eye gaze may impact memory by manipulating the eye gaze of a live speaker in the context of a traditional recognition paradigm used frequently in the laboratory. A female (Experiment 1) or male (Experiment 2) investigator read words aloud and varied whether eye contact was, or was not, made with a participant. With both female and male investigators, eye contact improved word recognition only for female participants and hindered word recognition in male participants. When a female investigator prolonged their eye contact (Experiment 3) to provide a longer opportunity to both observe and process the investigator’s eye gaze, the results replicated the findings from Experiments 1 and 2. The findings from Experiments 1–3 suggest that females interpret and use the investigator’s eye gaze differently than males. When key aspects from the previous experiments were replicated in a noncommunicative situation (i.e., when a video of a speaker is used instead of a live speaker; Experiment 4), the memory effects observed previously in response to eye gaze were eliminated. Together, these studies suggest that it is the socially communicative aspects of eye gaze from a real person that influence memory. The findings reveal the importance of using social cues that are communicative in nature (e.g., real people) when studying the relationship between social attention and memory

    Reflexiones de estudiantes universitarios, docentes de Agroecología (U.N.Cuyo) y agentes de extensión del INTA en prácticas de intervención socioproductivas en las zonas de Luján de Cuyo y Valle de Uco, Mendoza

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    En el marco de la asignatura Agroecología y Ambientes Rurales de la carrera en Ingeniería en Recursos Naturales Renovables (FCA- UNCuyo), se han realizado durante 10 años académicos consecutivos, dos actividades consistentes en visitar a diferentes tipos sociales agrarios ubicados en Luján de Cuyo y el Valle de Uco. En las nombradas actividades, los estudiantes realizan una visita extendida a productores que integran diferentes cadenas productivas, con el objetivo de caracterizar el ecosistema, sociosistema y tecnosistema en cada caso, además de diferenciar manejos convencionales y agroecológicos. Con la información recabada y reflexionada, los estudiantes realizan un trabajo integrador, con carácter de condición obligatoria para rendir el examen final de la asignatura, que rescata una problemática detectada y propone una solución socio tecnológica con base agroecológica, ajustada a las características de tipo social agrario abordado. El nombrado material queda a disposición de los actores involucrados para ser utilizado como una herramienta de comprensión de la dinámica socio-productiva y territorial. En el presente relato realizamos una breve síntesis sobre las experiencias de cada visita a campo y se presentan las reflexiones de los actores involucrados acerca de esta experiencia.In the framework of agroecology and rural environments race course in Engineering in Renewable Natural Resources (FCA UNCuyo) were performed for 10 consecutive school years, two consistent activities visit different agricultural social types are located in Lujan de Cuyo and Uco Valley. In the named activities, students made an extended visit to producers that integrate different production chains, in order to characterize the ecosystem, sociosistema and Technosystem in each case, in addition to conventional agro differentiate and handling. With the information gathered and reflected, students take an integrative work, as an obligatory condition to take the final exam of the subject, who rescues a detected problem and proposes a solution partner agroecologically technological basis and adjusted to the characteristics of a social nature agricultural addressed. The named material is available to the actors involved to be used as a tool for understanding the socio-productive and territorial dynamics. In this story is a brief summary of experiences of each field visit and reflections of stakeholders about this experience are presented.Eje: A2: Paisajes, Territorios y AgroecologíaFacultad de Ciencias Agrarias y Forestale

    Reflexiones de estudiantes universitarios, docentes de Agroecología (U.N.Cuyo) y agentes de extensión del INTA en prácticas de intervención socioproductivas en las zonas de Luján de Cuyo y Valle de Uco, Mendoza

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    En el marco de la asignatura Agroecología y Ambientes Rurales de la carrera en Ingeniería en Recursos Naturales Renovables (FCA- UNCuyo), se han realizado durante 10 años académicos consecutivos, dos actividades consistentes en visitar a diferentes tipos sociales agrarios ubicados en Luján de Cuyo y el Valle de Uco. En las nombradas actividades, los estudiantes realizan una visita extendida a productores que integran diferentes cadenas productivas, con el objetivo de caracterizar el ecosistema, sociosistema y tecnosistema en cada caso, además de diferenciar manejos convencionales y agroecológicos. Con la información recabada y reflexionada, los estudiantes realizan un trabajo integrador, con carácter de condición obligatoria para rendir el examen final de la asignatura, que rescata una problemática detectada y propone una solución socio tecnológica con base agroecológica, ajustada a las características de tipo social agrario abordado. El nombrado material queda a disposición de los actores involucrados para ser utilizado como una herramienta de comprensión de la dinámica socio-productiva y territorial. En el presente relato realizamos una breve síntesis sobre las experiencias de cada visita a campo y se presentan las reflexiones de los actores involucrados acerca de esta experiencia.In the framework of agroecology and rural environments race course in Engineering in Renewable Natural Resources (FCA UNCuyo) were performed for 10 consecutive school years, two consistent activities visit different agricultural social types are located in Lujan de Cuyo and Uco Valley. In the named activities, students made an extended visit to producers that integrate different production chains, in order to characterize the ecosystem, sociosistema and Technosystem in each case, in addition to conventional agro differentiate and handling. With the information gathered and reflected, students take an integrative work, as an obligatory condition to take the final exam of the subject, who rescues a detected problem and proposes a solution partner agroecologically technological basis and adjusted to the characteristics of a social nature agricultural addressed. The named material is available to the actors involved to be used as a tool for understanding the socio-productive and territorial dynamics. In this story is a brief summary of experiences of each field visit and reflections of stakeholders about this experience are presented.Eje: A2: Paisajes, Territorios y AgroecologíaFacultad de Ciencias Agrarias y Forestale

    Reflexiones de estudiantes universitarios, docentes de Agroecología (U.N.Cuyo) y agentes de extensión del INTA en prácticas de intervención socioproductivas en las zonas de Luján de Cuyo y Valle de Uco, Mendoza

    Get PDF
    En el marco de la asignatura Agroecología y Ambientes Rurales de la carrera en Ingeniería en Recursos Naturales Renovables (FCA- UNCuyo), se han realizado durante 10 años académicos consecutivos, dos actividades consistentes en visitar a diferentes tipos sociales agrarios ubicados en Luján de Cuyo y el Valle de Uco. En las nombradas actividades, los estudiantes realizan una visita extendida a productores que integran diferentes cadenas productivas, con el objetivo de caracterizar el ecosistema, sociosistema y tecnosistema en cada caso, además de diferenciar manejos convencionales y agroecológicos. Con la información recabada y reflexionada, los estudiantes realizan un trabajo integrador, con carácter de condición obligatoria para rendir el examen final de la asignatura, que rescata una problemática detectada y propone una solución socio tecnológica con base agroecológica, ajustada a las características de tipo social agrario abordado. El nombrado material queda a disposición de los actores involucrados para ser utilizado como una herramienta de comprensión de la dinámica socio-productiva y territorial. En el presente relato realizamos una breve síntesis sobre las experiencias de cada visita a campo y se presentan las reflexiones de los actores involucrados acerca de esta experiencia.In the framework of agroecology and rural environments race course in Engineering in Renewable Natural Resources (FCA UNCuyo) were performed for 10 consecutive school years, two consistent activities visit different agricultural social types are located in Lujan de Cuyo and Uco Valley. In the named activities, students made an extended visit to producers that integrate different production chains, in order to characterize the ecosystem, sociosistema and Technosystem in each case, in addition to conventional agro differentiate and handling. With the information gathered and reflected, students take an integrative work, as an obligatory condition to take the final exam of the subject, who rescues a detected problem and proposes a solution partner agroecologically technological basis and adjusted to the characteristics of a social nature agricultural addressed. The named material is available to the actors involved to be used as a tool for understanding the socio-productive and territorial dynamics. In this story is a brief summary of experiences of each field visit and reflections of stakeholders about this experience are presented.Eje: A2: Paisajes, Territorios y AgroecologíaFacultad de Ciencias Agrarias y Forestale
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