Engineering topics

Fischer, Michael

Publications and source records attributed to Fischer, Michael.

5 records

DOE OSTI2017

Structural basis of Notch O-glucosylation and O–xylosylation by mammalian protein–O-glucosyltransferase 1 (POGLUT1)

Protein O-glucosyltransferase 1/Rumi-mediated glucosylation of Notch epidermal growth factor-like (EGF-like) domains plays an important role in Notch signaling. Protein O-glucosyltransferase 1 shows specificity for folded EGF-like domains, it can only glycosylate serine residues in the C 1 XSXPC 2 motif, and it possesses an uncommon dual donor substrate specificity. Using several EGF-like domains and donor substrate analogs, we have determined the structures of human Protein O-glucosyltransferase 1 substrate/product complexes that provide mechanistic insight into the basis for these properties. Notably, we show that Protein O-glucosyltransferase 1’s requirement for folded EGF-like domains also leads to its serine specificity and that two distinct local conformational states are likely responsible for its ability to transfer both glucose and xylose. We also show that Protein O-glucosyltransferase 1 possesses the potential to xylosylate a much broader range of EGF-like domain substrates than was previously thought. Finally, we show that Protein O-glucosyltransferase 1 has co-evolved with EGF-like domains of the type found in Notch.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Observing cellulose biosynthesis and membrane translocation in crystallo

Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. Here, in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA–BcsB complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate- and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a ‘finger helix’ that contacts the polymer’s terminal glucose. Cooperating with BcsA’s gating loop, the finger helix moves ‘up’ and ‘down’ in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA’s transmembrane channel. Finally, this mechanism is validated experimentally by tethering BcsA’s finger helix, which inhibits polymer translocation but not elongation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Loss mechanisms in superconducting thin film microwave resonators

We present a systematic analysis of the internal losses of superconducting coplanar waveguide microwave resonators based on niobium thin films on silicon substrates. In particular, we investigate losses introduced by Nb/Al interfaces in the center conductor, which is important for experiments where Al based Josephson junctions are integrated into Nb based circuits. We find that these interfaces can be a strong source for two-level state (TLS) losses, when the interfaces are not positioned at current nodes of the resonator. In addition to TLS losses, for resonators including Al, quasiparticle losses become relevant above 200 mK. Finally, we investigate how losses generated by eddy currents in conductive material on the backside of the substrate can be minimized by using thick enough substrates or metals with high conductivity on the substrate backside.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2015

Thermal expansion of mullite-type Bi{sub 2}Al{sub 4}O{sub 9}: A study by X-ray diffraction, vibrational spectroscopy and density functional theory

Polycrystalline Bi{sub 2}Al{sub 4}O{sub 9} powder samples were synthesized using the glycerine method. Single crystals were produced from the powder product in a Bi{sub 2}O{sub 3} melt. The lattice thermal expansion of the mullite-type compound was studied using X-ray diffraction, Raman spectroscopy and density functional theory (DFT). The metric parameters were modeled using Grüneisen approximation for the zero pressure equation of state, where the temperature-dependent vibrational internal energy was calculated from the Debye characteristic frequency. Both the first-order and second-order Grüneisen approximations were applied for modeling the volumetric expansion, and the second-order approach provided physically meaningful axial parameters. The phonon density of states as well as phonon dispersion guided to set the characteristic frequency for simulation. The experimental infrared and Raman phonon bands were compared with those calculate from the DFT calculations. Selective Raman modes were analyzed for the thermal anharmonic behaviors using simplified Klemens model. The respective mode Grüneisen parameters were calculated from the pressure-dependent Raman spectra. - Graphical abstract: Crystal structure of mullite-type Bi{sub 2}Al{sub 4}O{sub 9} showing the edge-sharing AlO{sub 6} octahedra running parallel to the c-axis. - Highlights: • Thermal expansion of Bi{sub 2}Al{sub 4}O{sub 9} was studied using XRD, FTIR, Raman and DFT. • Metric parameters were modeled using Grüneisen approximation. • Phonon DOS and phonon dispersion helped to set the Debye frequency. • Mode Grüneisen parameters were calculated from the pressure-dependent Raman spectra. • Anharmonicity was analyzed for some selective Raman modes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRS2006

High Performance, Dependable Multiprocessor

With the ever increasing demand for higher bandwidth and processing capacity of today's space exploration, space science, and defense missions, the ability to efficiently apply commercial-off-the-shelf (COTS) processors for on-board computing is now a critical need. In response to this need, NASA's New Millennium Program office has commissioned the development of Dependable Multiprocessor (DM) technology for use in payload and robotic missions. The Dependable Multiprocessor technology is a COTS-based, power efficient, high performance, highly dependable, fault tolerant cluster computer. To date, Honeywell has successfully demonstrated a TRL4 prototype of the Dependable Multiprocessor [I], and is now working on the development of a TRLS prototype. For the present effort Honeywell has teamed up with the University of Florida's High-performance Computing and Simulation (HCS) Lab, and together the team has demonstrated major elements of the Dependable Multiprocessor TRLS system.

fault tolerant↗