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Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. Methods: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. Results: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. Conclusions: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

OBJECTIVE: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. METHODS: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. RESULTS: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. CONCLUSIONS: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

This work sought to use inductive thermal plasmas to deposit superelastic alloys from a wire source. It was found that unbiased sources could not be heated sufficiently at the tip to produce a measurable deposition rate. NiTi and Cu films were deposited at very low rates (on the order of 10 nm/min) using roughly 200 VDC applied to the wire relative to the substrate. Thermal modeling suggests that pulse biasing is necessary to achieve high deposition rates.

Thermal management systems using two-phase heat transfer loops are being developed for application on future spacecraft operating at high power levels. Design of these systems requires a knowledge of two-phase flow and heat transfer in microgravity and high acceleration environments. In addition to the two-phase flow parameters, several criteria including heat transfer boundaries and instability mechanisms are expected to be strongly dependent on the acceleration levels. These should be analyzed in detail and experimentally verified. The overall objective of this program was to identify the parameters and criteria of immediate importance of design of two-phase systems and to develop the conceptual design for a modular two-phase loop which can be used to generate the necessary data. A survey of existing and ongoing efforts was performed to identify the areas that need more testing, and to select the two- phase flow models which could be used in the design analysis. A preliminary design for a baseline configuration was completed which is intended to perform the defined experiments at earth gravity and aboard an airplane in Keplerian trajectory. This effort consisted of fluid selection, design analysis, and specification of the test matrix. Keywords: Hydrodynamic instability; Spacecraft heat transfer; Critical heat flux. (edc)

In 1981-1983 a computer program was developed which solves numerically two-dimensional Euler equations using the Godunov method. The program was intended primarily for turbomachinery application, but with modification to the boundary conditions, application to any problem which is modeled by the Euler equations is possible. This report covers one year of extensive testing of the code for different flow regimes. This testing was done with three main objectives: a) To gain experience in simulation of the various problems related to the research activity in the Turbopropulsion Laboratory, Naval Postgraduate School, Monterey, California; b) To test code accuracy by comparing numerical with analytical solutions; and c) To find the source of errors for various numerical simulations and the basic Godunov method in order to reduce these errors.

The flow to the rotor of a single stage axial transonic compressor was found to be in disagreement with design requirements. The incidence angle to the rotor blading was measured to be towards stall in the hub and tip regions when close to design near center-span. Hardware modifications were made, guided by flow field calculations. Predictions were compared with measurements. The most significant improvement was obtained by increasing the flow rate at open throttle. No practical method to correct the flow near the hub was found. Keywords: MERIDL computer program; Transonic compressor; Inlet flow field; Distortion screens.

A 0.28-m single stage transonic fan was operated in a rotor only configuration. Overall performance was measured and radial distributions of inlet and outlet velocity were obtained using time-averaging combination temperature-pneumatic probes. These results were compared to the prediction of a finite element computer code (TURBOFEM) prediction. The blade-to-blade velocity and pressure distributions were measured using the Dual Probe Digital Sampling technique (involving two commercial semi-conductor probes of simple design). Data were obtained from hub-to-tip at both near-sonic and at supersonic inlet relative Mach numbers. The rotor losses were derived as blade-to-blade distributions and the shock losses were evaluated as components of the total loss at each radius. Based on the limited data obtained near sonic conditions, a combination of the profile loss model of Koch & Smith and shock loss model of Dunker was found to predict the measured radial loss distribution quite well. Preliminary observations of rotor shock oscillations were also reported. Keywords: Axial flow compressors, Compressor rotors, Compressor stators, Transonic flow, Turbomachinery flow fields, Transonic loss measurements, and Finite element codes.

A one-dimensional Euler code for solving the unsteady, inviscid, compressible flow in wave rotor devices is described. The Random Choice Method program (RCM) implemented in the code is shown to be very suitable for describing the multiple discontinuities and wave interactions in these flows. The modular structure of the program allows studying different 'families' of wave diagrams quickly and inexpensively. Example applications are included. Keywords: Fluid flow; and Finite difference equations. (Author)

This work sought to verify concepts used in the design of a large scale, low speed, radial cascade wind tunnel which was to be used to investigate flow phenomena in and the performance of vaned radial diffusors. A major contributor to centrifugal compressor efficiency is the performance of the vaned diffusor which closely follows the impeller of the compressor. The purpose of this diffusor is to efficiently convert most of the kinetic energy of the transonic flow entering the vane into pressure. The need for an experimental facility which could simulate adequately, at low cost and in a controlled way, the environment of the centrifugal compressor motivated the development of the Centrifugal Diffusor Test Device (CDTD). It was expected that the generation of a three dimensional flow would provide improved empirical data on annular cascade performance. This measurement program surveyed the axial and circumferential uniformity of the flow at the inlet of a transonic wedge-type blading mounted in the device. Evaluation of the results showed the flow uniformity to be unsatisfactory. Leakage and other small perturbations in the flow field in the swirl generator are believed to be amplified by the basic flow configuration of the device. Keywords: CDTD(Centrifugal Diffuser Test Device), Swirl vanes, Centrifugal diffuser, Flow measurements, Flow models.

The power of future spacecraft are expected to grow considerably in the near future, and this will require more efficient thermal transport techniques. Due to high heat transfer coefficient, two-phase gas-liquid loops are expected to be used for removal and transport of heat to space radiators. The design of such cooling systems requires a knowledge of two-phase flow and heat transfer at reduced and zero gravities. The objective of this study was to develop or extend the earth gravity models for the two-phase friction multiplier, the void quantity relation, and the forced convective heat transfer coefficient to zero gravity situations. Turbulent mixing length theory was used to develop a model for the two-phase fluid and heat transfer parameters. The velocity, density, and temperature distributions were derived by solving the conservation equations for a continuous medium and assuming equal turbulent exchanges of momentum, density, and heat. The flow was assumed to be locally homogeneous, and the void distribution was allowed to vary within the channel. The results show that the model predicts all the correct physical trends. The model contains a free parameter which should be specified from experiments at zero gravity, simulated zero gravity, or conditions where the effect of gravity can be neglected. Additional keywords: Equations; Weightlessness.

More effective and efficient thermal transport techniques will be needed for heat rejection from equipment on satellites. Circulating two-phase fluid loops have been suggested and laboratory tested for possible application in the above areas. In comparison to a single-phase loop, the two-phase system operates at considerably smaller flow rates and maintains a tighter temperature control with higher heat transfer coefficients. However, the two-phase fluid flow regimes, pressure gradients and heat transfer coefficients must be evaluated for application in the weightless environment of an orbiting satellite. This projecting studies two-phase flow behavior under zero gravity conditions. The overall objectives of this study were to generate a data base for two-phase pressure drop and the void-quality relationship under simulated zero gravity conditions and to develop analytical models to predict these parameters for bubbly and annular flow. The simulation of zero gravity two-phase flow was achieved by using two immiscible liquids with equal densities to eliminate the buoyancy component. Although this approach does not eliminate the gravity effects, it provides a representation for void distribution in the absence of gravity. The modeling effort is limited to developing relations for the two-phase friction multiplier and void-quality relation under bubbly and annular flow conditions. The bubbly flow model is based on the assumption of local homogeneous conditions between the phases but allows for void distribution in the radial direction. Separated flow conservation equations are used, and single-phase turbulent flow eddy diffusivity relations are employed.

The objective of this research program was to determine the feasibility of using a Spindt type thin film emitter chip to produce amperes of low voltage modulated current at tens of kilovolt beam voltage for a space application. The specific requirement was for a pulse modulated column of electrons of 10 amperes current at 50 kilovolts voltage. A design effort determined that a 2-inch diameter chip would be required to provide this current with conservative emission current density. A conceptual design was developed consisting of an array of emitting regions producing beamlets which were to be accelerated through a gridded or perforated anode at approximately 3 kilovolt voltage, followed by post-acceleration to 50 kilovolts. Feasibility was to be demonstrated by using smaller (1/2-inch square) standard emitter chip of the type produced by SRI International for their field emissions research program. This chip was to be tested to the same current density as would be required of the 2-inch chip. A test electron gun employing a standard emitter chip was designed and fabricated based on the results of a computer-derive electron optics model. Of five emitter chips started by two were successful and were delivered for use in the test gun. One chip was lost during assembly of the test gun due to breakdown of the chip, apparently from RF leakage while a welding process was being performed. After modifying the construction procedure, the test gun was successfully assembled. However, during tests this chip failed catastrophically at one percent of the current emission which was required to demonstrate feasibility of the approach.