146 research outputs found

    Guidance and Navigation Challenges for a Mars Ascent Vehicle

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    This work presents studies and analysis in support of a Mars Ascent Vehicle as part of a Martian Sample Return campaign. The vehicle design has been ongoing, with rapid development of a 6 Degree of Freedom simulation to capture full vehicle dispersions and integrated performance of vehicle, guidance, navigation and control. The maturation of this simulation is presented to provide an overview of its capabilities added over the past year of effort. The results describe in detail guidance algorithm development to increase the systems robustness to thrust sensitivities. Navigation performance and sensitivity analysis are included to describe the capabilities of the current design as well as identify primary drivers of insertion performance. Lastly, integrated vehicle 6DOF statistical results are presented to provide insight into the nominal performance of the current vehicle and insight into system-level drivers. Future work is described to outline the continuing maturation and development of the MSR MAV ascent vehicle

    The JanDY Survey System

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    JanDY is a survey system built by students and faculty from Hope College’s Computer Science Department. It is the program that runs behind the scenes during the Student Assessment of Learning & Teaching surveys that all students take each semester, which are used by the institution and instructors to evaluate the effectiveness of all courses at Hope. The current system was built using the outdated Google Web Toolkit. Our goal was to build a new version of JanDY using a more modern web framework, AngularJS. Beyond updating the technologies used in the system, we also added new functionality, including an interface for the creation and editing of surveys. In order to ensure that our new system was reliable we constructed a comprehensive test suite in the development process, testing our web application and load handling with tools such as Mockito, Jasmine, Karma, and JMeter

    Using an Embedded System for a Quality Cup of Coffee

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    Many coffee lovers spend up to 5onacupofcoffeeeveryday.Tosavemoneyonecouldmakethemathome,butaqualitymachinewithPIDsstartat5 on a cup of coffee everyday. To save money one could make them at home, but a quality machine with PIDs start at 1000. Using an embedded system one could spend less than 50andafewhoursimplementPIDsintoanexisting50 and a few hours implement PIDs into an existing 400 machine that will last a lifetime. microcontroller. Learning C language combined with hardware implementation applied to cheap and simple everyday objects can improve everyday quality of life and save money. This is challenging because we have to incorporate the additional circuitry into a pre established circuit with limited space, and tie in new code. In addition to the PID controls that are commonly found on high-end espresso machines, Our team decided to implement a touch screen interface, which required programming using a proprietary IDE and language. The resulting product is able to match temperature and pressure consistency levels that are found in competing machines. When we added in programmability of pre-infusion we start to compete with machines in the $5000 range, like the La Marzocco GS3, but we go even further with a touch screen interface, and the ability to plot temperature and pressure over time on the included LCD screen

    Hydrogen bonding in aqueous solution and peptide helicity studied using model systems

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    Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.Includes bibliographical references.by Evan T. Powers.Ph.D

    The proteostasis boundary in misfolding diseases of membrane traffic

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    AbstractProtein function is regulated by the proteostasis network (PN) [Balch, W.E., Morimoto, R.I., Dillin, A. and Kelly, J.W. (2008) Adapting proteostasis for disease intervention. Science 319, 916‚Äď919], an integrated biological system that generates and protects the protein fold. The composition of the PN is regulated by signaling pathways including the unfolded protein response (UPR), the heat-shock response (HSR), the ubiquitin proteasome system (UPS) and epigenetic programs. Mismanagement of protein folding and function during membrane trafficking through the exocytic and endocytic pathways of eukaryotic cells by the PN is responsible for a wide range of diseases that include, among others, lysosomal storage diseases, myelination diseases, cystic fibrosis, systemic amyloidoses such as light chain myeloma, and neurodegenerative diseases including Alzheimer‚Äôs. Toxicity from misfolding can be cell autonomous (affect the producing cell) or cell non-autonomous (affect a non-producing cell) or both, and have either a loss-of-function or gain-of-toxic function phenotype. Herein, we review the role of the PN and its regulatory transcriptional circuitry likely to be operational in managing the protein fold and function during membrane trafficking. We emphasize the enabling principle of a ‚Äėproteostasis boundary (PB)‚Äô [Powers, E.T., Morimoto, R.T., Dillin, A., Kelly, J.W., and Balch, W.E. (2009) Biochemical and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78, 959‚Äď991]. The PB is defined by the combined effects of the kinetics and thermodynamics of folding and the kinetics of misfolding, which are linked to the variable and adjustable PN capacity found different cell types. Differences in the PN account for the versatility of protein folding and function in health, and the cellular and tissue response to mutation and environmental challenges in disease. We discuss how manipulation of the folding energetics or the PB through metabolites and pharmacological intervention provides multiple routes for restoration of biological function in trafficking disease

    Internally heated and fully compressible convection: flow morphology and scaling laws

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    In stars and planets natural processes heat convective flows in the bulk of a convective region rather than at hard boundaries. By characterizing how convective dynamics are determined by the strength of an internal heating source we can gain insight into the processes driving astrophysical convection. Internally heated convection has been studied extensively in incompressible fluids, but the effects of stratification and compressibility have not been examined in detail. In this work, we study fully compressible convection driven by a spatially uniform heating source in 2D and 3D Cartesian, hydrodynamic simulations. We use a fixed temperature upper boundary condition which results in a system that is internally heated in the bulk and cooled at the top. We find that the flow speed, as measured by the Mach number, and turbulence, as measured by the Reynolds number, can be independently controlled by separately varying the characteristic temperature gradient from internal heating and the diffusivities. 2D simulations at a fixed Mach number (flow speed) demonstrate consistent power at low wavenumber as diffusivities are decreased. We observe convection where the velocity distribution is skewed towards cold, fast downflows, and that the flow speed is related to the length scale and entropy gradient of the upper boundary where the downflows are driven. We additionally find a heat transport scaling law which is consistent with prior incompressible work.Comment: 22 pages, 12 figures, submitted to Phys. Rev. Fluid

    Individual and Collective Contributions of Chaperoning and Degradation to Protein Homeostasis in E. coli

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    SummaryThe folding fate of a protein in vivo is determined by the interplay between a protein’s folding energy landscape and the actions of the proteostasis network, including molecular chaperones and degradation enzymes. The mechanisms of individual components of the E. coli proteostasis network have been studied extensively, but much less is known about how they function as a system. We used an integrated experimental and computational approach to quantitatively analyze the folding outcomes (native folding versus aggregation versus degradation) of three test proteins biosynthesized in E. coli under a variety of conditions. Overexpression of the entire proteostasis network benefited all three test proteins, but the effect of upregulating individual chaperones or the major degradation enzyme, Lon, varied for proteins with different biophysical properties. In sum, the impact of the E. coli proteostasis network is a consequence of concerted action by the Hsp70 system (DnaK/DnaJ/GrpE), the Hsp60 system (GroEL/GroES), and Lon

    Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity

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    SummaryN-Glycosylation plays an important role in protein folding and function. Previous studies demonstrate that a phenylalanine residue introduced at the n-2 position relative to an Asn-Xxx-Thr/Ser N-glycosylation sequon increases the glycan occupancy of the sequon in insect cells. Here, we show that any aromatic residue at n-2 increases glycan occupancy in human cells and that this effect is dependent upon oligosaccharyltransferase substrate preferences rather than differences in other cellular processing events such as degradation or trafficking. Moreover, aromatic residues at n-2 alter glycan processing in the Golgi, producing proteins with less complex N-glycan structures. These results demonstrate that manipulating the sequence space surrounding N-glycosylation sequons is useful both for controlling glycosylation efficiency, thus enhancing glycan occupancy, and for influencing the N-glycan structures produced

    Semi-Quantitative Models for Identifying Potent and Selective Transthyretin Amyloidogenesis Inhibitors

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    Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state‚ÄĒthereby inhibiting amyloidogenesis. Herein, we use previously reported structure-activity relationship data to develop two semi-quantitative algorithms for identifying the structures of potent and selective transthyretin kinetic stabilizers/amyloidogenesis inhibitors. The viability of these prediction algorithms, in particular the more robust in silico docking model, is perhaps best validated by the clinical success of tafamidis, the first-in-class drug approved in Europe, Japan, South America, and elsewhere for treating transthyretin aggregation-associated familial amyloid polyneuropathy. Tafamidis is also being evaluated in a fully-enrolled placebo-controlled clinical trial for its efficacy against TTR cardiomyopathy. These prediction algorithms will be useful for identifying second generation TTR kinetic stabilizers, should these be needed to ameliorate the central nervous system or ophthalmologic pathology caused by TTR aggregation in organs not accessed by oral tafamidis administration
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