Ground controlled precision landing delivery in the presence of radar disturbances

Originally presented as the author's thesis, (M.S.) in the M.I.T. Dept. of Aeronautics and Astronautics, 1977May 1977Includes bibliographical references (p. 51)Introduction: The purpose of Air Traffic Control is to ensure separation of aircraft in the most efficient manner possible. The need for efficiency is becoming more important as air traffic continues to increase at a high rate. Terminal area traffic control is the area in which the greatest amount of effort is expended since this tends to be the limiting factor in airspace congestion. The current Automated Radar Terminal System provides a monitoring function which was unheard of with previous systems. However, this is not sufficient in view of the increasing air traffic. More improvements are needed in the exchange of information between the ground controller and the aircraft. The proposed upgraded Air Traffic Control system will provide better data acquisition, communications service, and increased automation. Future systems should be capable of providing more complete automation in terms of command generation and delivery. These systems are called Strategic Navigation or Four-Dimensional Navigation. The principle of these systems is to assign a route-time profile to each aircraft thus providing good management of energy, space, and runways. This method utilizes a fixed airspace structure with a variable flight path to de-randomize aircraft runway arrival time. The method favored by the Federal Aviation Administration consists of ground computation of heading, altitude, and airspeed commands which are broadcast to the aircraft via digital data-link. These commands can be either visually displayed for manual operation by the pilot or at some future time directly tied into the aircraft auto-pilot. The purpose of this study is to simulate the flight of an aircraft on a terminal approach in a Four-Dimensional Navigation environment using discrete control commands. During the flight, position information is estimated from noisy radar observations. Speed is estimated from these observations and is used in a timed delivery algorithm to determine when to issue commands to the aircraft. Time control precision will be experimentally determined in the presence of the radar disturbance and accuracy of the Four-Dimensional Navigation task in the presence of this uncertainty will be quantified. A number of studies have previously been conducted to determine fix-to-fix and runway arrival time accuracy. These studies neglected the effect of wind and assumed perfect radar position information. For this reason a comprehensive model for these two effects was developed

Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine

Inactivated Foot-and-Mouth Disease (FMD) vaccine has proven to be effective in the control of the disease. However, its production has some disadvantages, including the costly biosafety facilities required for the production of huge amounts of growing live virus, the need of an exhaustive purification process to eliminate non-structural proteins of the virus in the final formulations in order to differentiate infected from vaccinated animals and variable local regulatory restrictions to produce and commercialize the vaccine. Thus, a novel vaccine against FMD that overcome these restrictions is desirable. Although many developments have been made in this regard, most of them failed in terms of efficacy or when considering their transferability to the industry. We have previously reported the use of transient gene expression in mammalian cells to produce FMD virus-like particles (VLPs) as a novel vaccine for FMD and demonstrated the immunogenicity of the recombinant structures in animal models. Here, we report the optimization of the production system by assaying different DNA:polyethylenimine concentrations, cell densities, and direct and indirect protocols of transfection. Also, we evaluated the reproducibility and scalability of the technology to produce high yields of recombinant VLPs in a cost-effective and scalable system compatible with industrial tech-transfer of an effective and safe vaccine.Estación Experimental Agropecuaria BarilocheFil: Mignaqui, Ana Clara. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche; ArgentinaFil: Ferella, Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Cass, Brian. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil Mukankurayija, Larissa. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: L’Abbé, Denis. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: Bisson, Louis. Human Health Therapeutics Research Center, National Research Council Canada; CanadaFil: Sánchez, Cintia. Biogénesis-Bagó; ArgentinaFil: Scian, Romina. Biogénesis-Bagó; ArgentinaFil: Cardillo, Sabrina Beatriz. Biogénesis-Bagó; ArgentinaFil: Durocher, Yves. Human Health Therapeutics Research Center, National Research Council Canada; CanadáFil: Wigdorovitz, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentin

Stable high volumetric production of glycosylated human recombinant IFNalpha2b in HEK293 cells

BACKGROUND: Mammalian cells are becoming the prevailing expression system for the production of recombinant proteins because of their capacity for proper protein folding, assembly, and post-translational modifications. These systems currently allow high volumetric production of monoclonal recombinant antibodies in the range of grams per litre. However their use for large-scale expression of cytokines typically results in much lower volumetric productivity. RESULTS: We have engineered a HEK293 cell clone for high level production of human recombinant glycosylated IFNα2b and developed a rapid and efficient method for its purification. This clone steadily produces more than 200 mg (up to 333 mg) of human recombinant IFNα2b per liter of serum-free culture, which can be purified by a single-step cation-exchange chromatography following media acidification and clarification. This rapid procedure yields 98% pure IFNα2b with a recovery greater than 70%. Purified IFNα2b migrates on SDS-PAGE as two species, a major 21 kDa band and a minor 19 kDa band. N-terminal sequences of both forms are identical and correspond to the expected mature protein. Purified IFNα2b elutes at neutral pH as a single peak with an apparent molecular weight of 44,000 Da as determined by size-exclusion chromatography. The presence of intramolecular and absence of intermolecular disulfide bridges is evidenced by the fact that non-reduced IFNα2b has a greater electrophoretic mobility than the reduced form. Treatment of purified IFNα2b with neuraminidase followed by O-glycosidase both increases electrophoretic mobility, indicating the presence of sialylated O-linked glycan. A detailed analysis of glycosylation by mass spectroscopy identifies disialylated and monosialylated forms as the major constituents of purified IFNα2b. Electron transfer dissociation (ETD) shows that the glycans are linked to the expected threonine at position 106. Other minor glycosylated forms and non-sialylated species are also detected, similar to IFNα2b produced naturally by lymphocytes. Further, the HEK293-produced IFNα2b is biologically active as shown with reporter gene and antiviral assays. CONCLUSION: These results show that the HEK293 cell line is an efficient and valuable host for the production of biologically active and glycosylated human IFNα2b

Use of stable CHO pools and CHO TGE to accelerate SARS-CoV-2 vaccine development

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Daily, biweekly, and seasonal temporal scales of pCO2 variability in two stratified Mediterranean reservoirs

Temporal scales of variability for the partial pressure of CO2 (pCO2) in the surface waters of two stratified Mediterranean reservoirs were examined through the temporal decomposition of 5 month time series with hourly sampling frequency. pCO2 time series included similar patterns of variability at daily,biweekly, and seasonal scales regardless of the difference in amplitude of the pCO2 variation in the two reservoirs studied. Daily variability was strongly related to the day-night cycles of metabolic activity, accounting for about one third of the total amplitude in pCO2 variation. At a biweekly scale, wind forcing led to higher rates of air-water CO2 exchange and subsequently temporary partial mixing events associated to relevant increase of CO2 concentration in surface waters. Seasonal variability accounted for one third of the amplitude of the pCO2 variability and was coupled to the seasonal dynamics of water temperature and thermal stratification of the water column. Our results provide evidence that CO2 emission from stratified water bodies shows significant variability at daily, biweekly, and seasonal scales; all of which should be taken into consideration in the analyses of the carbon fluxes. The wind-induced mixing events, operating at temporal scales between daily and seasonal cycles, may become a major factor controlling the pCO2 dynamics. Hence, some of the most common models for computing CO2 fluxes from pCO2 were not able to reproduce the biweekly response patterns of CO2 emissions to wind forcing

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized “Nouvelle-France” between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits