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Schalk, Martin. "Ultra-fast electronic pulse control at cryogenic temperatures." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAY061.
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Synchronisation ultra-rapide, mise en forme d’impulsions et commutation efficace sont au cœur des mesures précises. L’objectif de ce projet de thèse est d’apporter le contrôle électronique ultra-rapide aux circuits nanométriques refroidis à des températures de l’ordre du mK. L’opération quantique rapide rapprochera le domaine de l’optique électronique quantique de son homologue photonique avec des applications pour un contrôle électronique rapide et efficace des dispositifs quantiques. Les dispositifs expérimentaux développés au cours de ce projet de thèse sont décrits et testés de manière à esquisser également les possibilités d’intégration dans les technologies quantiques. Dans un premier temps, une impulsion de tension de forme lorentzienne Γ = (76 ± 2) ps est mesurée de manière résolue dans le domaine temporel à des températures cryogéniques. Ensuite, les dérives de phase et d’amplitude sont analysées et optimisé avec le spectre de bruit. Un nouveau dispositif de génération d’impulsions utilisant un générateur de peigne est ensuite décrit et testé. Enfin, un futur réalisation d’une expérience d’interférence quantique par manipulation et détection dans un conducteur quantique est décrite, de même que les défis posés pour les dispositives quantiques à basse température et ses interconnexionsUltra-fast synchronization, pulse shaping, and efficient switching are at the heart of precise measurements. The aim of this thesis project is to bring ultra-fast electronic control to small nano-metric circuits cooled down to mK temperatures. The fast quantum operation will bring the field of quantum-electronic optics closer to its photoniccounterpart with applications for fast and efficient electronic control in quantum devices. To this end, the experimental setups developed during the thesis project are described and tested in a way to outline also possible device integration for scalable solid-state quantum technology. As a first step, a Lorentzian-shaped voltage pulse with a full width half maximum Γ = (76 ± 2) ps is measured in a time-resolved manner at cryogenic temperatures. Secondly, the phase and amplitude drifts are analyzed and optimized together with the noise spectrum. A new pulse generation setup using a microwave frequency comb generator is then described and tested. Finally, a future realization of a quantum interference experiment by manipulating and detecting electronic pulses in a quantum conductor is described along with challenges for low-temperature quantum hardware and interconnects
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Van, Niekerk Philip Charl. "A Cryogenic CMOS-based Control System for Testing Superconductor Electronics." Thesis, Link to the online version, 2008. http://hdl.handle.net/10019/1338.
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MARTINEZ, ROJAS ALEJANDRO DAVID. "Integrated cryogenic electronics to readout large areas SiPMs." Doctoral thesis, Politecnico di Torino, 2021. http://hdl.handle.net/11583/2907032.
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Badenhorst, Le Roux. "Cryogenic amplifiers for interfacing superconductive systems to room temperature electronics." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/1586.
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Thesis (MScEng (Electrical and Electronic Engineering))--Stellenbosch University, 2008.This thesis is aimed at testing commercially available CMOS amplifier ICs at 4 K. Super Conducting Electronics (SCE) will also be used to amplify RSFQ signals for easier detection by CMOS technology and better signal-to-noise ratios. The SCE comprises of a Suzuki stack amplifier, a 250 μA JTL and a DC-to-SFQ converter. The Suzuki stack amplifier is simulated in WRSPICE. It is able to amplify an SFQ signal synchronised with an external clock signal. The amplified signal can then be detected by a normal commercially available CMOS amplifier IC. To keep the noise in the signal to a minimum, the commercial amplifier must be be situated as close as possible to the SCE. The amplifier must therefore be able to operate at 4 K. Ten different amplifier ICs were tested and three was found that worked down to 4 K.
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Langhammer, David. "On the chromogenic behavior of tungsten oxide films : A cryogenic experiment." Thesis, Uppsala universitet, Institutionen för kemi - Ångström, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-263554.
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The chromogenic properties of tungsten trioxide (WO3) have been studied by photoluminescence spectroscopy at 4.2 K in order to characterize the electronic structure of this material and see how this relates to optical responses during chromogenic coloration. Transition processes between electron energy states are often the cause of optical phenomena and it is important to identify such processes in order to understand the chromogenic coloration of tungsten oxide films. Much research work has been devoted to characterize the physical and chemical mechanisms that are responsible for this coloration and this is of fundamental importance to understand the chromogenic behavior. The latest research shows that oxygen vacancies could play an important role in certain coloration processes, but it is still a matter of debate whether these are important for the overall response. This work aims to identify specific transitions that are related to oxygen vacancies by measuring photoluminescence from films with controlled vacancy content. The main goal of the project was to set up an experiment that could measure photoluminescence at liquid helium temperature. This was done by installing and integrating the components included in this experimental set-up. The films had been prepared prior to this work and were deposited on a nanocrystalline CaF2 substrate, which is a material that has a very large band gap and was therefore expected to fully transparent in the UV range. However it was found that the substrate inelastically scattered the UV excitation light, which produced strong signals that overshadowed the photoluminescence and prevented an effective characterization of the electronic structure in the films. Instead, suggestions were given on how to minimize uncertainty factors and overcome the difficulties met in this work. It was also found that the films attain a lasting blue coloration by exposure to UV light in vacuum, and that this might be due to oxygen being desorbed from the film during experiments in vacuum.
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Sinthiptharakoon, K. "Investigation of individual donors in silicon at cryogenic temperature with atomic-scale resolution for atomic electronic devices." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1460900/.
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There is an urgent need for characterisation of group V donors in silicon necessary for the development of quantum information processing (QIP) devices, and my PhD work has been contributed towards this objective. In this thesis, three different group V donors were individually studied with scanning tunnelling microscopy (STM) and spectroscopy (STS), combined with DFT calculation and simulated STM images where necessary. Si(001) dosed with phosphine (PH3) at room temperature prior and imaged at 77 K a few minutes later was investigated. Novel phosphine-related features were observed and compared to the room-temperature results [4]. Some features were the same as the room-temperature dissociative products but a new dissociative mechanism was proposed and novel bonding configurations were assigned to the features. A transformation between adsorbates was seen to occur on the surface at 77 K and was attributed to a tip-induced effect. The appearance of the Si-P heterodimer was found to be different at 77 K and room temperature [5] and the reasons for this difference was discussed. Subsurface As and Bi donors below the Si(001):H surface were separately investigated at 77 K. Special sample annealing (flashing) procedures were created for both studies. There were two classes of As features commonly observed while there were three types for Bi. The appearance of the As features related to the As wavefunction informed that the subsurface As donors were electrically neutral but could be reversibly switched to being ionised (positively-charged) by changing the sample bias. Some subsurface As donors can also be negatively-charged, depending on their distances from the surface. DFT calculations were performed and simulated STM images were generated to compare with the experimental data, allowing us to assign the features to As donors at their exact lattice positions. The appearance of the Bi features indicated that the Bi donors were negatively-charged but could be changed to being positively-charged. With the unequal rate of tunnelling in and off the donor energy level, the Bi donors could be switched back to being negatively-charged again. The Bi wavefunction projection was speculated, based on the Bi features.
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Müller, David [Verfasser], Otto [Akademischer Betreuer] Dopfer, Otto [Gutachter] Dopfer, and Michael [Gutachter] Schmitt. "Electronic spectroscopy of flavins in a cryogenic 22 - pole ion trap / David Müller ; Gutachter: Otto Dopfer, Michael Schmitt ; Betreuer: Otto Dopfer." Berlin : Technische Universität Berlin, 2021. http://nbn-resolving.de/urn:nbn:de:101:1-2021092901572707449456.
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Rao, P. Sharath Chandra. "Analysis of fluid circulation in a spherical cryogenic storage tank and conjugate heat transfer in a circular microtube." [Tampa, Fla.] : University of South Florida, 2004. http://purl.fcla.edu/fcla/etd/SFE0000461.
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Reinke, Benjamin T. "Design, Characterization, and Simulation of a Cryogenic Irradiation Facility in the Ohio State University Research Reactor Pool." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437746576.
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Conrad, Theodore Judson. "Miniaturized pulse tube refrigerators." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/41108.
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Pulse tube refrigerators (PTR) are robust, rugged cryocoolers that do not have a moving component at their cold ends. They are often employed for cryogenic cooling of high performance electronics in space applications where reliability is paramount. Miniaturizing these refrigerators has been a subject of intense research interest because of the benefits of minimal size and weight for airborne operation and because miniature coolers would be an enabling technology for other applications. Despite much effort, the extent of possible PTR miniaturization is still uncertain.
To partially remedy this, an investigation of the miniaturization of pulse tube refrigerators has been undertaken using several numerical modeling techniques. In support of these models, experiments were performed to determine directional hydrodynamic parameters characteristic of stacked screens of #635 stainless steel and #325 phosphor bronze wire mesh, two fine-mesh porous materials suitable for use in the regenerator and heat exchanger components of miniature PTRs. Complete system level and pulse tube component level CFD models incorporating these parameters were then employed to quantitatively estimate the effects of several phenomena expected to impact the performance of miniature PTRs. These included the presence of preferential flow paths in an annular region near the regenerator wall and increased viscous and thermal boundary layer thicknesses relative to the pulse tube diameter. The effects of tapering or chamfering the junctions between components of dissimilar diameters were also investigated.
The results of these models were subsequently applied to produce successively smaller micro-scale PTR models having total volumes as small as 0.141 cc for which sufficient net cooling was predicted to make operation at cryogenic temperatures feasible.
The results of this investigation provide design criteria for miniaturized PTRs and establish the feasibility of their operation at frequencies up to 1000 Hz with dimensions roughly an order of magnitude smaller than those that have recently been demonstrated, provided that challenges related to their regenerator fillers and compressors can be addressed.
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Jego, Galahad. "TES résistif et électronique cryogénique de contre-réaction active associée." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS550.
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Depuis quelques années, le CSNSM d’Orsay est capable de fabriquer des pistes en niobium et silicium en méandres qui forment des microcalorimètres TES à haute résistivité (HRTES). La haute impédance permet l’utilisation d’une électronique de lecture à base de transistors. Cela simplifie le multiplexage et offre la possibilité de déplacer le premier étage de lecture à un étage plus chaud du cryogénérateur limitant alors la puissance Joule dissipée sur l’étage des thermomètres. Le travail de ce document vise à étudier la crédibilité des HRTES en tant que détecteur haute résolution à l’aide d’une contre-réaction active en proposant un modèle thermoélectrique résolu analytiquement et numériquement. Les paramètres de ce modèle sont déterminés expérimentalement. Les mesures de la résolution numérique du modèle sont confrontées aux mesures à l’équilibre thermique et lors d’une excitation thermique. Il donne des résultats très cohérents. La résolution analytique du modèle permet de faire des projections de résolution et d’optimisation du détecteur. La résolution théorique qui en découle ne s’oppose pas à l’objectif de moins de 2,5 eV d’Athéna. Cette étude indique aussi que la contre-réaction active réduit les effets du découplage électrons/phonons et stabilise le HRTES au point de polarisation souhaité. Elle encourage à poursuivre les efforts de développementSince a few years, CSNSM, Orsay, is capable of co-evaporating niobium and silicon into highly resistive TES (HRTES) meanders. This high impedance allows the use of transistors as readout electronics. The first stage of this electronics can be placed away from the thermometers reducing Joule power on the colder stage of the cryocooler. Also, multiplexing is greatly simplified. This manuscript aims to study the credibility of HRTES as high resolution microcalorimeters. A model of the HRTES and its active electrothermal feedback is resolved analytically and numerically. The parameters of this model are computed with experimental data. The numerical solving of the model is constantly compared to the thermal equilibrium and dynamic measured data. This comparison shows coherence between model and data. The analytical solving is used to compute a theoretical resolution and to optimize the detector. The resulting theoretical resolution does not conflict with Athena’s objective of less than 2.5 eV. It also shows that effects of the electrons/phonons decoupling are greatly reduced and that the HRTES can be stabilized at desired bias point. All of this work encourages further development efforts
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Yang, Shaoyong. "Cryogenic characteristics of IGBTs." Thesis, University of Birmingham, 2005. http://etheses.bham.ac.uk//id/eprint/896/.
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Applications are now starting to emerge for superconducting devices in the areas of electrical power conversion and management, for example superconducting windings for marine propulsion motors, superconducting fault current limiters and superconducting magnet energy storage (SMES). Many of these applications also require power electronics, and it is therefore timely to consider the possibility of locating the power electronics in the cryosystem with the superconducting devices. Although significant work has been undertaken on the cryogenic operation of small devices, little has been published on larger devices, particularly the IGBT. This therefore forms the focus of this study. To examine the cryogenic performance of the sample devices, a cryo-system consisting of a cold chamber, a helium-filled compressor and vacuum pumps was built. Static, gate charge and switching tests were carried out on three types of IGBT modules, PT (punch-through), NPT (non-punch-through) and IGBT3 respectively, in the temperature range of 50 to 300 K. The switching tests were undertaken at 600V and up to 110 A. A physically based, compact level-1 model was selected to model the cryogenic performance of the IGBTs. A generic Saber power diode model with reverse recovery was selected to model the diode cryogenic performance. Close correspondence was demonstrated between the models and experimental results over the temperature range of 50- 300 K. Saber simulation was used to examine the cryogenic performance of a DC-DC step-down converter and a pulse-width modulated inverter leg, in which the temperature-dependent power device models developed in the modelling work were used. The simulation results showed that standard power electronic circuits using standard devices could work much more efficiently at low temperatures, for example, the efficiency of the DC-DC converter working at 50 kHz being increased from 90.0% at room temperature to 97.0% at 50 K.
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Conway, Lamb Ian. "Cryogenic Control Beyond 100 Qubits." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/17046.
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Quantum computation has been a major focus of research in the past two decades, with recent experiments demonstrating basic algorithms on small numbers of qubits. A large-scale universal quantum computer would have a profound impact on science and technology, providing a solution to several problems intractable for classical computers. To realise such a machine, today's small experiments must be scaled up, and a system must be built which provides control and measurement of many hundreds of qubits. A device of this scale is challenging: qubits are highly sensitive to their environment, and sophisticated isolation techniques are required to preserve the qubits' fragile states. Solid-state qubits require deep-cryogenic cooling to suppress thermal excitations. Yet current state-of-the-art experiments use room-temperature electronics which are electrically connected to the qubits. This thesis investigates various scalable technologies and techniques which can be used to control quantum systems. With the requirements for semiconductor spin-qubits in mind, several custom electronic systems, to provide quantum control from deep cryogenic temperatures, are designed and measured. A system architecture is proposed for quantum control, providing a scalable approach to executing quantum algorithms on a large number of qubits. Control of a gallium arsenide qubit is demonstrated using a cryogenically operated FPGA driving custom gallium arsenide switches. The cryogenic performance of a commercial FPGA is measured, as the main logic processor in a cryogenic quantum control system, and digital-to-analog converters are analysed during cryogenic operation. Recent work towards a 100-qubit cryogenic control system is shown, including the design of interconnect solutions and multiplexing circuitry. With qubit fidelity over the fault-tolerant threshold for certain error correcting codes, accompanying control platforms will play a key role in the development of a scalable quantum machine.
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Ryan, Keith Patrick. "Rapid cryogenic fixation of biological specimens for electron microscopy." Thesis, University of Plymouth, 1991. http://hdl.handle.net/10026.1/2504.
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This thesis describes investigations into cryofixation by the plunge-cooling technique, at ambient pressure. The objective was to characterise coolants which are commonly used for cryofixation, so that the structure and chemistry of biological specimens may be preserved in a more life-like state. The work began with the design of a suitable cooling device. This was developed further into a large test-bed apparatus which was used in both biological and methodological experiments. The large cooling apparatus demonstrated for the first time that ethane was a superior coolant under forced convection, compared to propane or Freon 22, for bare thermocouples, for exposed hydrated specimens and for metal-sandwiched hydrated specimens. Ice crystal formation was monitored in sandwiched specimens and found to correspond closely to modelling predictions. A biological application was the X-ray microanalysis of body fluids in "indicator" species of Chaetognaths, where results obtained from cryoscanning electron microscopy revealed ecophysiological differences. The use of low thermal mass supports demonstrated that good freezing can occur in the centre of specimens. A new cryomounting method was developed to load well-frozen specimens into the microscope. The effect of post-freeze processing temperature was investigated by monitoring ice crystals in red blood cells. Exposure to 213 K (-60°C) over a 48 hour period did not induce crystal growth and exposure to 233 K (-40°C) for 8 days showed minimal ice crystal damage. The progress of cryosubstitution was monitored over 48 h at 193 K ( -80°C), this showed that uranium ingressed to a depth of 320 µm which could be doubled when shrinkage was allowed for. The conclusion was that observed ice crystal damage originated during the initial freezing and not during subsequent cryoprocessing.
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Fletcher, A. L. "Cryogenic developments and signal amplification in environmental scanning electron microscopy." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599080.
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This thesis describes the development of a cryogenic imaging system for an environmental scanning electron microscope (ESEM). The ESEM is an important new development in electron microscopy since it enables specimens to be viewed in a small pressure of gas - generally this gas is water vapour, although an alternative must be used for cryogenic applications. The presence of the gas also contributes to the imaging mechanism, a process whereby the signal electrons are amplified by the gaseous molecules prior to detection. The purpose of the cryogenic system was to image the complicated, four phase microstructure of ice cream. Although viewed routinely by conventional electron microscopy techniques, the harsh temperature and pressure regimes involved (around -120°C at 10.6 torr) increase the likelihood of introducing artefacts. Therefore, a methodology was developed for imaging ice cream with ESEM in a small pressure of an alternative imaging gas at a much warmer temperature of -80°C. In order to stabilise the ice phase in the samples at a higher temperatures, a system was designed for mixing gases, so that a small amount of water vapour could be mixed into the imaging gas. This system lifted the temperature restrictions of ice cream imaging so it can, in principle, now be imaged at its storage temperature of -20°C. In the search for alternative imaging gases to water vapour, questions were raised about the fundamental way in which the signal electrons interact with the gas. In order to understand the electron amplification properties of the different gases, a Faraday cage was designed and the electron amplification was investigated. We suggest that the ratio of the peak amplification to the plateau amplification gives a semi-quantitative method of determining the imaging quality of the gas. Furthermore, by isolating experimentally the effects of different components of the signal, it was found that the low energy secondary electrons dominate the signal at low pressure, whereas the effect of backscattered electrons becomes more important as the pressure is raised. In addition, the performance of two ESEM detector designs were compared. The new gaseous secondary electron detector (GSED), which was designed to reduce the contribution of some sources of signal, was found to achieve its aim, but some of its overall contrast was sacrificed when compared to the original environmental secondary detector (ESD).
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Jia, Chunjiang. "Experimental investigation of semiconductor losses in cryogenic DC-DC converters." Thesis, University of Birmingham, 2008. http://etheses.bham.ac.uk//id/eprint/161/.
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As high-temperature superconductor technology approaches commercial applications, for example superconducting magnetic energy storage, superconducting fault current limiters, and superconducting rotary machines for marine propulsion, it is timely to consider the possibility of integrating the associated control equipment into the cryostat with the superconductor. This may bring benefits in terms of the performance of the power electronics or may enable other system benefits such as higher voltage lower current feedthroughs which reduce heat leakage into the cryostat. This Thesis studies the performance of several DC-DC power conversion techniques at temperatures down to 20 K. In particular hard switching, synchronous rectifier, zero-voltageswitching and multi-level circuit prototypes are examined, focusing on the losses in the semiconductor devices. The prototypes operated from 120 V and 500 V DC supplies at power levels up to 500 W using MOSFET devices and ultrafast, Schottky and silicon carbide diodes. The semiconductors were all in commercial TO220 packages. Although MOSFET on-state resistance was found to drop by a factor of approximately six at cryogenic temperatures, the device switching speed and switching losses were relatively insensitive to temperature. The diode on-state voltage increased by 20-30 % at low temperatures whilst reverse recovery and the associated losses decreased by a factor of up to ten. The total semiconductor losses in all prototypes reduced at low temperatures, typically exhibiting a minimum value in the region of 50-100 K. The performance of the hard switching and synchronous rectifier circuits was limited at cryogenic temperatures by switching losses, even though the dead time in the synchronous rectifier was adjusted to compensate for the increase in MOSFET gate threshold voltage at low temperatures. The zero-voltage-switching prototype offered the largest reduction in semiconductor losses at low temperatures, the losses were reduced to 18 % of the room temperature value. Furthermore, since the remaining losses were almost entirely due to MOSFET conduction, further reductions could be easily achieved by paralleling additional devices. The performance of the multi-level circuits was limited by switching losses and the large number of series connected devices; however, a zero-voltage-switching synchronous rectifier variant of the circuit was suggested to overcome some of these limitations.
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Hussen, Walid Yass. "Investigation of the thermal and magnetic properties of some Ce-based heavy electron systems." Thesis, Loughborough University, 1990. https://dspace.lboro.ac.uk/2134/27939.
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The aim of this project was an investigation of the thermal and magnetic properties of highly correlated electron systems. To carry out the experiments it was necessary to design, construct and automate a calorimeter and a Faraday susceptibility balance. The calorimeter was used to determine the specific heat of powder samples from 1.5 K to 300 K using a pulse technique. Initially the performance of the calorimeter was verified using spectrographically pure copper samples. The specific heat of CePt2 and LaPt2 has been measured in the temperature range from 3 K to 100 K. The f-electron contribution to the specific heat of CePt2 was determined by subtracting the measured specific heat of isostructural LaPt2 from CePt2. This difference revealed a Schottky anomaly at temperatures between 15 K and 100 K. which enabled the crystal-field splitting of the J=5/2 ground state manifold of Ce3+ to be deduced.
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El, Kass Abdallah. "Milli-Kelvin Electronics at the Quantum-Classical Interface." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/26889.
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The primary research topic is the design of readout circuits for quantum systems at cryogenic temperatures. The work is divided into 3 parts.
The first part addresses the modelling of the I-V characteristics of the SiGe HBT over a wide range of temperatures. I empirically prove that the logarithmic slope of the collector current as a function of base-emitter bias is linearly dependent on the y-intercept over the temperature range from 300 K to 6 K. The forward active characteristics at different temperatures can be extrapolated to intersect at a single point. This point is labelled by its temperature-invariant voltage that is predicted to be very close to the bandgap potential at the junction.
The second part focuses on the scalability of on-chip readout of semiconductor qubits. I analyze the performance characteristics of a low-power common-emitter transimpedance amplifier. I simulate the electrical behaviour of the amplifier with 70 mK SiGe HBT literature data to understand the achievable fidelity and bandwidth of the readout. The analysis shows that sharper scaling of the transistor characteristics down to the mK range is required to lower the noise temperature of the amplifier below 1 K. I also explore the thermal ramifications of heat generation on the temperature of qubits. The results show a relation between readout circuit integration density and the qubit temperature.
Lastly, I present my work on designing, fabricating, and testing the QCPA for the purposes of amplifying qubit readout signals. The amplifier uses the capacitance between a metallic gate and the 2DEG in a GaAs/AlGaAs heterostructure as a medium of frequency mixing resulting in parametric amplification. The paramp, fabricated with the same semiconductor material and processing steps as qubits in GaAs, provides an on-chip, low-noise, wide dynamic range, and magnetically robust method for amplification at mK temperatures.
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Smit, Albert Bart. "A new femtosecond electron diffractometer for structural dynamics experiments at cryogenic temperatures." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/96015.
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Thesis (MSc)--Stellenbosch University, 2014.ENGLISH ABSTRACT: In this thesis, a femtosecond electron diffraction (FED) set-up that is capable of investigating the photo-induced switching of Cu(DCNQI)2 from being an insulator to being a conductor is presented. Movies of atomic structural changes with temporal resolution within the typical photo-switching transition timescales (sub-picoseconds) are obtainable with this set-up by employing a femtosecond laser. The experimental technique and the design of a crucial instrument of the machine, the electron gun, are extensively described and characterised both numerically and experimentally. The interest in observing atomic structural changes of Cu(DCNQI)2 in real time is because of the rich variety of the radical salts available that show alloy-specific Charge Density Wave (CDW) transitions. Valuable insights about the driving mechanisms behind these structural changes that are responsible for a change in conductivity are obtainable, as well as the relation between crystal alloys and their transition characteristics. Electron diffraction patterns of crystals in their metallic phase (room temperature) are shown in this thesis, but diffraction patterns of cryo-cooled Cu(DCNQI)2 in its insulating phase are still to be acquired. The temporal resolution of the atomic movie can be improved by recompression of electron pulses that are debunched due to Coulomb repulsion and electron energy spread within a pulse. Numerical and preliminary experimental results presented in this work expose the potential of a simple compression technique. In this way, more electrons in a single electron pulse can be afforded which allows to perform experiments at shorter integration time or lower repetition rate.
AFRIKAANSE OPSOMMING: In hierdie tesis word ’n femtosekonde elektron diffraksie opstelling aangebied wat daartoe in staat is om die foto-geïnduseerde omskakeling in Cu(DCNQI)2 van nie-geleier tot geleier te ondersoek. Deur gebruik te maak van ’n femtosekonde laser in hierdie opstelling, is ’rolprente’ van strukturele veranderinge op atoomskaal met ’n tyd resolusie beter as die tipiese foto-omskakelings tydskaal (sub-pikosekonde) verkrygbaar. Die eksperimentele tegniek en die ontwerp van ’n noodsaaklike instrument van die masjien, die elektron geweer, word breedvoerig beskryf en numeries en eksperimenteel gekenmerk. Die belangstelling om strukturele veranderinge in Cu(DCNQI)2 op atoom skaal in reële tyd waar te kan neem is as gevolg van die ryke verskeidenheid van radikale soute, wat allooispesifieke ladings digtheid golf (CDW) oorgange toon, wat beskikbaar is. Waardevolle insigte oor die meganismes wat hierdie strukturele veranderinge wat ’n verandering in geleiding veroorsaak dryf is verkrygbaar, sowel as die verwantskap tussen die kristal allooi en die oorgang kenmerke. Diffraksie patrone van kristalle in die metaalagtige fase (kamer temperatuur) word in hierdie tesis getoon, maar diffraksie patrone van cryo-verkoelde Cu(DCNQI)2 in die niegeleier fase moet nog verkry word. Die tyd resolusie van die atomiese rolprent kan verbeter word deur die elektron puls — wat deur Coulomb afstoting en elektron energie spreiding versprei is — weer saam te pers. Numeriese en voorlopige eksperimentele resultate toon die potensiaal van ’n eenvoudige kompressie tegniek. Hierdeur kan meer elektrone in ’n elektron puls gegun word en so die integrasie tyd of die herhalingstempo van die eksperimente verkort kan word.
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Tosaka, Masatoshi. "STRUCTURAL STUDY ON POLYMER CRYSTALS BY CRYOGENIC HIGH-RESOLUTION TRANSMISSION ELECTRON MICROSCOPY." Kyoto University, 2000. http://hdl.handle.net/2433/181349.
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Yuan, Jiahui. "SiGe HBTs Operating at Deep Cryogenic temperatures." Thesis, Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/14609.
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As Si-manufacturing compatible SiGe HBTs are making rapid in-roads into RF through mm-wave circuit applications, with performance levels steadily marching upward, the use of these devices under extreme environment conditions are being studied extensively. In this work, test structures of SiGe HBTs were designed and put into extremely low temperatures, and a new negative differential resistance effect and a novel collector current kink effect are investigated in the cryogenically-operated SiGe HBTs.
Theory based on an enhanced positive feedback mechanism associated with heterojunction barrier effect at deep cryogenic temperatures is proposed. The accumulated charge induced by the barrier effect acts at low temperatures to enhance the total collector current, indirectly producing both phenomena. This theory is confirmed using calibrated 2-D DESSIS simulations over temperature. These unique cryogenic effects also have significant impact on the ac performance of SiGe HBTs operating at high-injection. Technology evolution plays an important role in determining the magnitude of the observed phenomena, and the scaling implications are addressed. Circuit implication is discussed.
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Al-Taie, Haider. "Cryogenic on-chip multiplexer for the statistical study of quantum transport in low-dimensional devices." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708580.
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KUGATHASAN, RAMSHAN. "Low-Power Mixed-Signal ASIC for Cryogenic SiPM Readout." Doctoral thesis, Politecnico di Torino, 2020. http://hdl.handle.net/11583/2842523.
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Hodgdon, Travis K. "Cryogenic transmission electron microscopy as a probe of microstructural transitions in complex fluids." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 343 p, 2008. http://proquest.umi.com/pqdweb?did=1691645631&sid=3&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Shornikov, Andrey [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "An electron cooler for ultra-low energy cryogenic operation / Andrey Shornikov ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://d-nb.info/1179785029/34.
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Thakur, Ram-Krishna. "Study of Escape of Electrons from the Surface of Liquid 4Helium and Other Cryogenic Substrates." [S.l. : s.n.], 2006. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-37988.
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Dao, Nguyen Cong. "Characterisation and Modelling of Bulk CMOS Transistors over the 5 – 300 K Temperature Range." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17591.
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With the increasing interest in MOSFET device operation in extremely cold environments, circuit designs for low temperature applications have attracted recent attention. Device characterisation and modelling are crucial steps in circuit designs, and an appropriate approach for transistor characterisation at cryogenic temperatures is required to provide insight into transistor behaviour, and to develop reliable models for circuit simulations over the required operating temperatures. This work presents a detailed study of bulk CMOS transistors behaviour from room temperature down to 5 K. A new approach to extract intrinsic and extrinsic parameters of bulk CMOS over a wide range of temperature is proposed. Extracted MOSFET parameters reveal changing characteristics over the examined temperatures. Transistor characteristics are modelled based on physical properties of device and empirical results. This thesis introduces an enhanced MOSFET threshold model, based on a simplified Fermi potential and a field-assisted ionisation, derived from physics and experimental data. The model predicts the threshold voltage better than the conventional model, especially at low temperatures. An adapted carrier mobility model derived from a conventional model is experimentally verified. This work also presents a Verilog-A SPICE model based on the proposed models and extraction results. The SPICE model can be incorporated into Cadence Spectre simulator for circuit simulations at low temperatures. The SPICE model can replicate the I-V characteristics of the bulk CMOS over a wide temperature range. The matching of transistors is one of the most important aspects of high performance integrated circuit design. Results from this research reveal, for the first time, the matching properties of MOSFETs and its parameters over the 5-300 K temperature range. In addition, a new formula to calculate the current matching in bulk CMOS devices based on the threshold voltage, mobility and series resistance is introduced. The proposed formula obtained better results compared to the existing formula at low temperatures. The effects of device geometries on MOSFET parameter matching and current matching are also exposed. Matching results from PMOS and NMOS devices provide a view of device parameter variations from room temperature down to 5 K.
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Shen, Peter S. "The Characterization of Avian Polyomavirus, Satellite Tobacco Mosaic Virus, and Bacteriophage CW02 by Means of Cryogenic Electron Microscopy." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/3069.
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Viruses are the most abundant biological entity in the biosphere and are known to infect hosts from all domains of life. The aim of my work is to identify conserved and non-conserved features among the capsid structures of related and divergent icosahedral viruses via cryogenic electron microscopy, sequence analysis, molecular modeling, and other techniques. Bird polyomaviruses often cause severe disease in their hosts whereas mammalian polyomaviruses generally do not. Avian polyomavirus is a type of bird polyomavirus with an unusually broad host range compared to the restricted tropism of other polyomaviruses. Although most polyomaviruses have a conserved, rigid capsid protein structure, avian polyomavirus has a flexible capsid shell and a non-conserved C-terminus in its major capsid protein. A β-hairpin motif appears to stabilize other polyomaviruses but is missing in avian polyomavirus. The lack of this structure in avian polyomavirus may account for its capsid flexibility and broad host range. A minor capsid protein unique to bird polyomaviruses may be located on the inner capsid surface. This protein may have a role in the acute disease caused by bird polyomaviruses. The solution-state capsid structure of satellite tobacco mosaic virus was unexpectedly different than the previously solved crystalline structure. The conformational differences were accounted for by a shift of the capsid protein about the icosahedral fivefold axis. Conversely, the RNA core was consistent between solution and crystalline structures. The stable RNA core supports previous observations that the viral genome stabilizes the flexible capsid. Halophage CW02 infects Salinivibrio bacteria in the Great Salt Lake. The three-dimensional structure of CW02 revealed a conserved HK97-like fold that is found in all tailed, double-stranded DNA viruses. The capsid sequence of CW02 shares less than 20% identity with HK97-like viruses, demonstrating that structure is more conserved than sequence. A conserved module of genes places CW02 in the viral T7 supergroup, members of which are found in diverse aquatic environments. No tail structure was observed in reconstructions of CW02, but turret-like densities were found on each icosahedral vertex, which may represent unique adaptations similar to those seen in other extremophilic viruses.
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Colmenares, Juan. "Extreme Implementations of Wide-Bandgap Semiconductors in Power Electronics." Doctoral thesis, KTH, Elkraftteknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-192626.
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Wide-bandgap (WBG) semiconductor materials such as silicon carbide (SiC) and gallium-nitride (GaN) allow higher voltage ratings, lower on-state voltage drops, higher switching frequencies, and higher maximum temperatures. All these advantages make them an attractive choice when high-power density and high-efficiency converters are targeted. Two different gate-driver designs for SiC power devices are presented. First, a dual-function gate-driver for a power module populated with SiC junction field-effect transistors that finds a trade-off between fast switching speeds and a low oscillative performance has been presented and experimentally verified. Second, a gate-driver for SiC metal-oxide semiconductor field-effect transistors with a short-circuit protection scheme that is able to protect the converter against short-circuit conditions without compromising the switching performance during normal operation is presented and experimentally validated. The benefits and issues of using parallel-connection as the design strategy for high-efficiency and high-power converters have been presented. In order to evaluate parallel connection, a 312 kVA three-phase SiC inverter with an efficiency of 99.3 % has been designed, built, and experimentally verified. If parallel connection is chosen as design direction, an undesired trade-off between reliability and efficiency is introduced. A reliability analysis has been performed, which has shown that the gate-source voltage stress determines the reliability of the entire system. Decreasing the positive gate-source voltage could increase the reliability without significantly affecting the efficiency. If high-temperature applications are considered, relatively little attention has been paid to passive components for harsh environments. This thesis also addresses high-temperature operation. The high-temperature performance of two different designs of inductors have been tested up to 600_C. Finally, a GaN power field-effect transistor was characterized down to cryogenic temperatures. An 85 % reduction of the on-state resistance was measured at −195_C. Finally, an experimental evaluation of a 1 kW singlephase inverter at low temperatures was performed. A 33 % reduction in losses compared to room temperature was achieved at rated power.QC 20160922
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Yuan, Jiahui. "Cryogenic operation of silicon-germanium heterojunction bipolar transistors and its relation to scaling and optimization." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33837.
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The objective of the proposed work is to study the behavior of SiGe HBTs at cryogenic temperatures and its relation to device scaling and optimization. Not only is cryogenic operation of these devices required by space missions, but characterizing their cryogenic behavior also helps to investigate the performance limits of SiGe HBTs and provides essential information for further device scaling. Technology computer aided design (TCAD) and sophisticated on-wafer DC and RF measurements are essential in this research.
Drift-diffusion (DD) theory is used to investigate a novel negative differential resistance (NDR) effect and a collector current kink effect in first-generation SiGe HBTs at deep cryogenic temperatures. A theory of positive feedback due to the enhanced heterojunction barrier effect at deep cryogenic temperatures is proposed to explain such effects. Intricate design of the germanium and base doping profiles can greatly suppress both carrier freezeout and the heterojunction barrier effect, leading to a significant improvement in the DC and RF performance for NASA lunar missions.
Furthermore, cooling is used as a tuning knob to better understand the performance limits of SiGe HBTs. The consequences of cooling SiGe HBTs are in many ways similar to those of combined vertical and lateral device scaling. A case study of low-temperature DC and RF performance of prototype fourth-generation SiGe HBTs is presented. This study summarizes the performance of all three prototypes of these fourth-generation SiGe HBTs within the temperature range of 4.5 to 300 K. Temperature dependence of a fourth-generation SiGe CML gate delay is also examined, leading to record performance of Si-based IC. This work helps to analyze the key optimization issues associated with device scaling to terahertz speeds at room temperature. As an alternative method, an fT -doubler technique is presented as an attempt to reach half-terahertz speeds. In addition, a roadmap for terahertz device scaling is given, and the potential relevant physics associated with future device scaling are examined. Subsequently, a novel superjunction collector design is proposed for higher breakdown voltages. Hydrodynamic models are used for the TCAD studies that complete this part of the work. Finally, Monte Carlo simulations are explored in the analysis of aggressively-scaled SiGe HBTs.
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Vogel, Stephen [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "Developments at an Electrostatic Cryogenic Storage Ring for Electron-Cooled keV Energy Ion Beams / Stephen Vogel ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2016. http://d-nb.info/1180610571/34.
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Paul, Daniel Roman [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "Electron recombination studies of rotationally cold CH+ ions at the Cryogenic Storage Ring / Daniel Roman Paul ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2021. http://d-nb.info/1238361943/34.
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Hornibrook, John Murray. "Readout and Control Beyond a Few Qubits: Scaling-up Solid State Quantum Systems." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14448.
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Quantum entanglement and superposition, in addition to revealing interesting physics in their own right, can be harnessed as computational resources in a machine, enabling a range of algorithms for classically intractable problems. In recent years, experiments with small numbers of qubits have been demonstrated in a range of solid-state systems, but this is far from the numbers required to realise a useful quantum computer. In addition to the qubits themselves, quantum operation requires a host of classical electronics for control and readout, and current techniques used in few-qubit systems are not scalable. This thesis presents a series of techniques for control and readout of solid-state qubits, working towards scalability by integrating classical control with the quantum technology. Two techniques for reducing the footprint associated with readout of gallium arsenide spin qubits are demonstrated. Gate electrodes, used to define the quantum dot, are also shown to be sensitive state detectors. These gate-sensors, and the more conventional Quantum Point Contacts, are then multiplexed in the frequency domain, where three-channel qubit readout and ten-channel QPC readout are demonstrated. Two types of superconducting devices are also explored. The loss in superconducting coplanar waveguide resonators is measured, and a suppression of coupling to the parasitic electromagnetic environment is demonstrated. The thesis also details software for the simulation of Josephson-junction based circuits including features beyond what is available in commercial products. Finally, an architecture for managing control of a scalable machine is proposed where classical components are distributed throughout a cryostat and cryogenic switches route control pulses to the appropriate qubits. A simple implementation of the architecture is demonstrated that incorporates a double quantum dot, a gallium arsenide switch matrix, frequency multiplexed readout, and cryogenic classical computation.
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Saurabh, Sunny [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "Collision studies with internally cold ion beams and merged electron beams in a cryogenic storage ring / Sunny Saurabh ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1191758516/34.
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Bordin, Alberto. "Machinability of Ti6Al4V alloy produced by electron beam melting under different lubricating conditions." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3427109.
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In the last decade, the growing diffusion of metal additive manufacturing technologies is revolutionising the manufacturing processes of the most advanced industrial fields. Nowadays, more and more companies operating in the aeronautic and in the biomedical field are employing the additive manufacturing technology of Electron Beam Melting (EBM) to produce prosthesis and aero engine parts made of the titanium alloy Ti6Al4V, traditionally produced by hot forging and machining. Thanks to this technology, it is possible to realise a complex shape component with tailored mechanical and geometrical properties, passing from the 3D CAD model directly to the near net shape geometry without any intermediate manufacturing steps, thus cutting the production costs. However, finishing machining operations are still necessary to remove the surface porosity that is a direct and inevitable consequence of additive manufacturing technologies, and to achieve higher surface quality and geometrical accuracy. Aiming to optimize the machining operation and to avoid detrimental surface damages left on the final product, the material machinability has to be taken into account. At the moment, many efforts coming from both the academic and industrial research have been spent to enhance the poor machinability of wrought Ti6Al4V alloy due to the increasing demand from the aeronautic field; however no published works and technical data are available regarding the machinability of EBM Ti6Al4V that presents different mechanical properties. Within the biomedical field, the surgical replacements made of Ti6Al4V are traditionally machined under flood coolants, made of synthetic or vegetable oil and water emulsions. As a consequence, costly sterilizing and cleaning operations are performed to remove the toxic and pollutant chemical residuals left on the finished products at the end of the manufacturing process. Thus, there is a need to revise the traditional lubricating strategies applied in machining operations of surgical implants, proposing an innovative solution that might satisfy technological, environmental and economic issues.
In this PhD thesis, an innovative cryogenic cooling line has been developed and implemented to turn EBM Ti6Al4V alloy, as a promising alternative to standard cooling methods applied in machining surgical implants. The alloy machinability has been firstly investigated trough an experimental approach, evaluating the effects of three different cooling methods namely: dry, wet and cryogenic and of different cutting parameters, on the tool wear, on the surface integrity and on the chip morphology. Subsequently, a FE numerical model has been developed to simulate the turning operation of EBM Ti6Al4V alloy, capable to predict the effects of different process conditions.
Due to the beneficial effects induced by the cryogenic cooling on the surface integrity of turned Ti6AL4V EBM test pieces, the feasibility of such technology for biomedical applications has been validated by means of wear tests: the wear resistance of cryogenically machined specimens clearly increased with a strong reduction of metallic particles loss. Finally, cryogenic turning has been employed to machine real acetabular cups, in comparison with standard cooling methods applied in machining surgical implants. The beneficial effects imparted by cryogenic cooling in terms of improved material machinability, improved wear resistance and satisfying achievable geometrical accuracy, foresee a potential applicability of this technology in the biomedical field for years to come.Nell'ultimo decennio la crescente diffusione delle moderne tecnologie di formatura additiva da polvere metallica sta rivoluzionando i processi produttivi dei più avanzati settori manifatturieri. Oggigiorno, sempre più aziende operanti nel settore aeronautico e biomedicale stanno impiegando la tecnologia additiva denominata “Electron Beam Melting” per realizzare protesi ortopediche e componenti di motori aeronautici in lega di Ti6Al4V, tradizionalmente ottenuti per forgiatura e lavorazioni alle macchine utensili. Grazie a tale tecnologia, è possibile realizzare un componente di forma complessa, con proprietà geometriche e meccaniche taylorizzate, passando direttamente dal disegno al prodotto semi finito senza passaggi intermedi, abbattendo i costi di produzione. Tuttavia, lavorazioni alle macchine utensili di finitura sono tuttora necessarie per eliminare la porosità superficiale intrinseca a tale tecnologia e per ottenere una qualità superficiale e una precisione dimensionale non raggiungibili altrimenti. Al fine di ottimizzare la lavorazione meccanica e non indurre danneggiamenti superficiali al prodotto finito che ne inficiano la vita di servizio, è fondamentale conoscere la lavorabilità del materiale. Allo stato attuale, molti lavori di carattere scientifico e industriale sono stati condotti per migliorare la bassa lavorabilità della lega Ti6Al4V lavorata a caldo, grazie a una forte domanda dal settore aeronautico, ma non sono reperibili documenti e informazioni tecniche fruibili sul comportamento della lega prodotta per Electron Beam Melting, che manifesta differenti proprietà microstrutturali e meccaniche. Nel campo biomedicale, le protesi ortopediche in lega di Ti6Al4V sono lavorate alle macchine utensili applicando abbondante lubrificazione, realizzata con emulsioni di olio sintetico o vegetale e acqua. Al fine di rimuovere le sostanze tossico-inquinanti lasciate dalla lavorazione sui prodotti finiti, costose operazioni di lavaggio e sterilizzazione sono eseguite a fine processo. Nasce quindi l’esigenza di rivisitare le tradizionali strategie di lubrificazione impiegate nei processi di asportazione di truciolo in campo biomedicale, proponendo una soluzione che soddisfi dei requisiti tecnologici (bassa lavorabilità della lega), ambientali (fluido lubrificante non inquinante e tossico per l’uomo) ed economici (che riduca i costi di lavaggio e sterilizzazione). In questa tesi di dottorato, un sistema di lubrificazione criogenico è stato implementato per realizzare la tornitura della lega Ti6Al4V EBM, come alternativa da applicarsi in campo biomedicale. La lavorabilità della lega è stata investigata mediante un approccio sperimentale, valutando gli effetti di tre regimi di lubrificazione: a secco, lubrificante standard e mediante azoto liquido; e dei parametri di taglio, valutando l’usura dell’utensile, l’integrità superficiale e la morfologia del truciolo. In seguito un modello numerico agli elementi finiti è stato sviluppato per simulare il processo di tornitura su tale lega, capace di predire gli effetti di diversi parametri di processo. Visti i benefici apportati dalla lubrificazione criogenica sull'integrità superficiale di componenti torniti di Ti6AL4V EBM, l’applicabilità di tale tecnologia in campo biomedicale è stata validata mediante delle prove di usura: la resistenza all’usura del materiale è risultata notevolmente incrementata con minor rilascio di particelle metalliche. In fine, la tornitura criogenica è stata applicata nella lavorazione di reali coppe acetabolari, comparandone gli effetti con le più tradizionali strategie di lubrificazione. I positivi risultati in termini di miglioramento della lavorabilità, di resistenza all'usura accompagnati da soddisfacente precisione dimensionale, fanno intravvedere un’efficiente applicazione della tornitura criogenica in campo biomedicale negli anni futuri.
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Meyer, Christian [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "The lowest rotational quantum states of hydroxyl anions probed by electron photodetachment in a cryogenic storage ring / Christian Meyer ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177385864/34.
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Wilhelm, Patrick Udo [Verfasser], and Andreas [Akademischer Betreuer] Wolf. "First Studies of Low-Energy Electron Cooling of keV Energy Ion Beams at the Electrostatic Cryogenic Storage Ring CSR / Patrick Udo Wilhelm ; Betreuer: Andreas Wolf." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/1191758532/34.
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Rizvi, Syed Asad Ali. "Design of Novel Molecular Micelles for Capillary Electrophoresis." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/5.
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The research presented in this dissertation involves the synthesis, characterization, and application of novel anionic and cationic chiral molecular micelles in capillary electrophoresis (CE) for the separation of diverse chiral compounds. Chapter 1 presents brief overview of the surfactants, micelle polymer, CE and micellar electrokinetic chromatography (MEKC). Chapter 2 describes the simultaneous enantioseparation of eight single chiral center â-blockers using two novel leucine and isoleucine based polymeric surfactants. The simultaneous enantioseparation of multichiral center bearing â-blockers, nadolol and labetalol is described in chapter 3. A synergistic approach, using a combination of polysodium N-undecenoxycarbonyl-L-isoleucinate (poly-L-SUCIL) and sulfated â-CD showed dramatic enantioseparation of four stereoisomers of nadolol. On the other hand for labetalol, enantiomeric separation remains unaffected using the dual chiral selector system. Chapter 4 deals with the enantiomeric separation of the binaphthyl derivatives that was found to be influenced by pH, type and concentration of the background electrolyte as well as concentration of the polymeric surfactant. In chapter 5, characterization of five alkenoxy leucine-based surfactants with variations in chain length (C8-C11), polymerization concentration and degree of polymerization showed significant effects on the chiral resolution and efficiency of hydrophobic â-blockers. The synthesis and characterization of two positively charged amino acid derived chiral ionic liquids (ILs) and their corresponding polymers is presented in chapter 6. Chiral separation of two acidic analyte (difficult to resolve with anionic micelles) can be achieved with both monomers and polymers of ILs. In chapter 7, the synthesis and detailed characterization of three pH independent amino acids derived (L-leucinol, L-isoleucinol and L-valinol) sulfated chiral polymeric surfactants is presented. These chiral sulfated surfactants are thoroughly characterized and the morphological behavior of polymeric sulfated surfactants is revealed using cryogenic high-resolution electron microscopy. The work clearly demonstrates for the first time the superiority of chiral separation in MEKC coupled to mass spectrometry at low pH. Finally, in chapter 8, six amino acid derived chiral surfactants with carboxylate and sulfate head groups were compared for enantioseparation of broad range of structurally diverse racemic compounds at neutral and basic pH conditions.
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Akhtar, Sultan. "Transmission Electron Microscopy of Graphene and Hydrated Biomaterial Nanostructures : Novel Techniques and Analysis." Doctoral thesis, Uppsala universitet, Tillämpad materialvetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171991.
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Transmission Electron Microscopy (TEM) on light element materials and soft matters is problematic due to electron irradiation damage and low contrast. In this doctoral thesis techniques were developed to address some of those issues and successfully characterize these materials at high resolution. These techniques were demonstrated on graphene flakes, DNA/magnetic beads and a number of water containing biomaterials. The details of these studies are given below. A TEM based method was presented for thickness characterization of graphene flakes. For the thickness characterization, the dynamical theory of electron diffraction is used to obtain an analytical expression for the intensity of the transmitted electron beam as a function of thickness. From JEMS simulations (experiments) the absorption constant λ in a low symmetry orientation was found to be ~ 208 nm (225 ± 9 nm). When compared to standard techniques for thickness determination of graphene/graphite, the method has the advantage of being relatively simple, fast and requiring only the acquisition of bright-field (BF) images. Using the proposed method, it is possible to measure the thickness change due to one monolayer of graphene if the flake has uniform thickness over a larger area. A real-space TEM study on magnetic bead-DNA coil interaction was conducted and a statistical analysis of the number of beads attached to the DNA-coils was performed. The average number of beads per DNA coil was calculated around 6 and slightly above 2 for samples with 40 nm and 130 nm beads, respectively. These results are in good agreement with magnetic measurements. In addition, the TEM analysis supported an earlier hypothesis that 40 nm beads are preferably attached interior of the DNA-coils while 130 nm beads closer to the exterior of the coils. A focused ion-beam in-situ lift-out technique for hydrated biological specimens was developed for cryo-TEM. The technique was demonstrated on frozen Aspergillus niger spores which were frozen with liquid nitrogen to preserve their cellular structures. A thin lamella was prepared, lifted out and welded to a TEM grid. Once the lamella was thinned to electron transparency, the grid was cryogenically transferred to the TEM using a cryo-transfer bath. The structure of the cells was revealed by BF imaging. Also, a series of energy filtered images was acquired and C, N and Mn elemental maps were produced. Furthermore, 3 Å lattice fringes of the underlying Al support were successfully resolved by high resolution imaging, confirming that the technique has the potential to extract structural information down to the atomic scale. The experimental protocol is ready now to be employed on a large variety of samples e.g. soft/hard matter interfaces.
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Farrell, Jason. "The influence of cation doping on the electronic properties of Sr₃Ru₂O₇." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/689.
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Roberts, Anthony M. "Implementing a Piezoelectric Transformer for a Ferroelectric Phase Shifter Circuit." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1337025849.
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Rengnez, Florentin. "Développement de comparateur cryogénique de courants très faible bruit pour la métrologie électrique quantique." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLN009/document.
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Dans un contexte de besoin grandissant en précision dans la mesure des faibles courants pour les instituts nationaux de métrologie, l’industrie, les fabricants d’instruments et la physique fondamentale, l’étude des dispositifs à un électron (SET) capables de générer un courant continu directement proportionnel à une fréquence et la charge élémentaire, couplés à un amplificateur de courant très performant, le comparateur cryogénique de courant (CCC), devient pertinente pour réaliser un étalon quantique de courant. Dans ce contexte, les travaux ont été poursuivis au LNE sur l’étude de nouveaux dispositifs SET et le développement de nouveaux CCC. Durant cette thèse, un montage expérimental a été mis en place afin d’évaluer les performances d’un nouveau CCC, constitué d’une conception originale et de 30 000 tours. Les résultats expérimentaux obtenus sont satisfaisant par rapport aux objectifs fixés, que ce soit en termes de résolution en courant, d’erreurs, de stabilité des mesures et de reproductibilité. Le CCC développé durant la thèse peut donc être utilisé pour quantifier de manière métrologique les dispositifs à un électron. De plus, une modélisation réalisée à partir d’un schéma électrique équivalent a été mis en place afin de simuler le comportement réel du CCC en prenant en compte les aspects magnétiques et électriques mis en jeu. Cette simulation a permis la quantification de l’erreur due aux fuites de courants au travers des capacités parasites entourant les enroulements. Les résultats de la simulation indiquent que cette erreur atteint 10 10 à la fréquence de travail, ce qui est inférieure de deux ordres de grandeurs à l’erreur maximale tolérable : 10-8. Les résultats expérimentaux et de modélisation fournissent de nouveaux éléments d’amélioration de la conception de CCCs de grand gain. Enfin, la modélisation développée, une fois insérée dans une routine d’optimisation, pourra aussi être un outil de conception des CCCs très utileIn a context of growing need of precision in measuring low currents for national metrology institutes, industry, instrument manufacturers and fundamental physics, study of single-electron tunneling (SET) devices capable of generating a direct current directly proportional to the frequency and the elementary charge, coupled with a high performance current amplifier, the cryogenic current comparator (CCC), becomes relevant to realize a quantum current standard. In this framework, at LNE, study of new SET devices and the development of CCCs continues. In this thesis, an experimental setup was implemented to evaluate the performance of a new CCC, consisting of a new design and 30 000 turns. The experimental results fulfill our goals, whether in terms of current resolution, errors, measurement stability and reproducibility. The CCC developed during the thesis can thus be used to metrologically quantify SET devices. In addition, a model based on an equivalent circuit diagram has been developed to simulate the actual behavior of the CCC, taking into account the magnetic and electrical aspects involved. This simulation allows the quantification of the error due to currents leakage through parasitic capacitances surrounding the windings. Results of the simulation indicate that this error reaches 10 10, which is less, by two orders of magnitude, than the maximum tolerable error: 10 8. Results obtained experimentally and by simulation provide new improvement elements in the design of high ratio CCCs. The developed model, once inserted into an optimization routine, can also be a very useful design tool of CCCs
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Chaaban, Abdul Amir. "Etude de l'organisation structurale des nanocolloïdes humiques." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30062/document.
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L'organisation des substances humiques à l'échelle moléculaire reste une question largement débattue, et à ce jour, il n'a pas été possible de trancher entre une structure polymérique en pelotte plus ou moins flexible et un assemblage supramoléculaire de molecules hétérogènes associées par des liaisons hydrogènes et des interactions hydrophobes. Dans cette thèse, nous étudions la reconformation induite par l'addition de tensio-actifs cationiques (Chlorure de C n-trimethylammonium) sur une série de substances humiques (acides fulvique et humiques) ainsi que sur de la matière organique naturelle contenue dans des eaux noires. Des mesures de turbidité, de diffusion de lumière, mobilité électrophorétique, tension de surface, spectroscopie de fluorescence, diffusion des neutrons aux petits angles, et cryomicroscopie à transmission, permettent de decrire les complexes formés entre le tensio-actif et la matière humique. L'association matière humique/tensio-actif dépend à la fois d'interactions d'origine électrostatique et hydrophobe. Une série de structures moléculaires, vésicules, disques, globules, pseudo-micelles, est observée en cryomicroscopie selon la concentration en surfactant. La séquence obtenue est cohérente avec un système catanionique, en d'autres termes une partie de la matière humique est amphiphile et s'organise en assemblage supramoléculaire. L'addition de tensio-actif modifie également fortement le spectre de fluorescence de la matière humique, les nouvelles bandes bien résolues présentes sur le spectre indiquant une restructuration majeure de l'assemblage supramoléculaireThe structural organization of humic nanocolloids remains a matter of harsh debate, and surprisingly, it is yet not possible to decide between an arrangement of the humic matter in the form of randomly coiled macromolecules more or less connected, and a supramolecular organization of small heterogeneous molecules linked by hydrogen bonds and hydrophobic interactions. In this study, we investigate the reconformation induced by the addition of cationic surfactants (C n-trimethylammonium chloride) of varying alkyl chain length with a series of humic substances (HS) and Dissolved Organic matter (DOM) from two blackwater rivers of the Central Amazon. Turbidity measurements, Dynamic light scattering, electrophoretic mobility, surface tension, fluorescence spectroscopy, small angle neutron scattering and cryo-transmission electron microscopy (cryo-TEM), are combined to describe the Humic Substance/Surfactant complexes obtained. The association between the oppositely charged HS and cationic surfactant is driven by both electrostatic and hydrophobic interactions. A variety of molecular structures, unilamellar vesicles, disks, globules, spheroidal micelles, are visualized by cryo-TEM depending on surfactant concentration. Such sequence, consistent with those displayed by catanionic systems, provides an independent confirmation of both the amphiphilic nature of HS and of its supramolecular organization. In addition, the molecular rearrangement was investigated using single-scan fluorescence emission spectra spectroscopy, thus identifying the chemical groups responsible for the fluorescence properties in HS and DOM. The addition of cationic surfactant to HS/DOM unveils an unexpected fine structure of humic-like fluorescence through new emission peaks that are not evidenced in the references HS/DOM. An enhanced protein-like fluorescence indicating major restructuration and structural stacking/de-stacking is observed. All our results support a supramolecular organization of humic substances and DOM
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Otto, Ernst. "Development of superconducting bolometer device technology for millimeter-wave cosmology instruments." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:30a1103a-ea7a-4b08-ba92-665cbd9740e0.
Full textAbstract:
The Cold-Electron Bolometer (CEB) is a sensitive detector of millimeter-wave radiation, in which tunnel junctions are used as temperature sensors of a nanoscale normal metal strip absorber. The absorber is fed by an antenna via two Superconductor-Insulator-Normal metal (SIN) tunnel junctions, fabricated at both ends of the absorber. Incoming photons excite electrons, heating the whole electron system. The incoming RF power is determined by measuring the tunneling current through the SIN junctions. Since electrons at highest energy levels escape the absorber through the tunnel junctions, it causes cooling of the absorber. This electron cooling provides electro-thermal feedback that makes the saturation power of a CEB well above that of other types of millimeter-wave receivers. The key features of CEB detectors are high sensitivity, large dynamic range, fast response, easy integration in arrays on planar substrates, and simple readout. The high dynamic range allows the detector to operate under relatively high background levels. In this thesis, we present the development and successful operation of CEB, focusing on the fabrication technology and different implementations of the CEB for efficient detection of electromagnetic signals. We present the CEB detector integrated across a unilateral finline deposited on a planar substrate. We have measured the finline-integrated CEB performance at 280-315 mK using a calibrated black-body source mounted inside the cryostat. The results have demonstrated strong response to the incoming RF power and reasonable sensitivity. We also present CEB devices fabricated with advanced technologies and integrated in log-periodic, double-dipole and cross-slot antennas. The measured CEB performance satisfied the requirements of the balloon-borne experiment BOOMERANG and could be considered for future balloon-borne and ground-based instruments. In this thesis we also investigated a planar phase switch integrated in a back-to-back finline for modulating the polarization of weak electromagnetic signals. We examine the switching characteristics and demonstrate that the switching speed of the device is well above the speed required for phase modulation in astronomical instruments. We also investigated the combination of a detector and a superconducting phase switch for modulating the polarization of electromagnetic radiation.
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Venkataraman, Sunitha. "Systematic Analysis of the Small-Signal and Broadband Noise Performance of Highly Scaled Silicon-Based Field-Effect Transistors." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16232.
Full textAbstract:
The objective of this work is to provide a comprehensive analysis of the small-signal and broadband noise performance of highly scaled silicon-based field-effect transistors (FETs), and develop high-frequency noise models for robust radio frequency (RF) circuit design. An analytical RF noise model is developed and implemented for scaled Si-CMOS devices, using a direct extraction procedure based on the linear two-port noise theory.
This research also focuses on investigating the applicability of modern CMOS technologies for extreme environment electronics. A thorough analysis of the DC, small-signal AC, and broadband noise performance of 0.18 um and 130 nm Si-CMOS devices operating at cryogenic temperatures is presented. The room temperature RF noise model is extended to model the high-frequency noise performance of scaled MOSFETs at temperatures down to 77 K and 10 K. Significant performance enhancement at cryogenic temperatures is demonstrated, indicating the suitability of scaled CMOS technologies for low temperature electronics. The hot-carrier reliability of MOSFETs at cryogenic temperatures is investigated and the worst-case gate voltage stress condition is determined. The degradation due to hot-carrier-induced interface-state creation is identified as the dominant degradation mechanism at room temperature down to 77 K. The effect of high-energy proton radiation on the DC, AC, and RF noise performance of 130 nm CMOS devices is studied. The performance degradation is investigated up to an equivalent total dose of 1 Mrad, which represents the worst case condition for many earth-orbiting and planetary missions.
The geometric scaling of MOSFETs has been augmented by the introduction of novel FET designs, such as the Si/SiGe MODFETs. A comprehensive characterization and modeling of the small-signal and high-frequency noise performance of highly scaled Si/SiGe n-MODFETs is presented. The effect of gate shot noise is incorporated in the broadband noise model. SiGe MODFETs offer the potential for high-speed and low-voltage operation at high frequencies and hence are attractive devices for future RF and mixed-signal applications.
This work advances the state-of-the-art in the understanding and analysis of the RF performance of highly scaled Si-CMOS devices as well as emerging technologies, such as Si/SiGe MODFETs. The key contribution of this dissertation is to provide a robust framework for the systematic characterization, analysis and modeling of the small-signal and RF noise performance of scaled Si-MOSFETs and Si/SiGe MODFETs both for mainstream and extreme-environment applications.
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Huisman, Maximiliaan. "Vision Beyond Optics: Standardization, Evaluation and Innovation for Fluorescence Microscopy in Life Sciences." eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1017.
Full textAbstract:
Fluorescence microscopy is an essential tool in biomedical sciences that allows specific molecules to be visualized in the complex and crowded environment of cells. The continuous introduction of new imaging techniques makes microscopes more powerful and versatile, but there is more than meets the eye. In addition to develop- ing new methods, we can work towards getting the most out of existing data and technologies. By harnessing unused potential, this work aims to increase the richness, reliability, and power of fluorescence microscopy data in three key ways: through standardization, evaluation and innovation.
A universal standard makes it easier to assess, compare and analyze imaging data – from the level of a single laboratory to the broader life sciences community. We propose a data-standard for fluorescence microscopy that can increase the confidence in experimental results, facilitate the exchange of data, and maximize compatibility with current and future data analysis techniques.
Cutting-edge imaging technologies often rely on sophisticated hardware and multi-layered algorithms for reconstruction and analysis. Consequently, the trustworthiness of new methods can be difficult to assess. To evaluate the reliability and limitations of complex methods, quantitative analyses – such as the one present here for the 3D SPEED method – are paramount.
The limited resolution of optical microscopes prevents direct observation of macro- molecules like DNA and RNA. We present a multi-color, achromatic, cryogenic fluorescence microscope that has the potential to produce multi-color images with sub-nanometer precision. This innovation would move fluorescence imaging beyond the limitations of optics and into the world of molecular resolution.
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Sylvestre, Alain. "Evolution des proprietes electriques et physiques aux basses temperatures de transistors a effet de champ a heterojonction a grille courte sur substrat inp." Paris 11, 1996. http://www.theses.fr/1996PA112020.
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Cette these presente une etude experimentale a temperature ambiante et aux temperatures cryogeniques de transistors a effet de champ a heterojonctions (hemts) inalas/ingaas/inalas en accord de maille et pseudomorphiques sur substrat inp, de longueur de grille submicronique. Malgre des performances microondes a l'etat de l'art, ces composants souffrent d'une technologie encore immature qui rend difficile une bonne reproductibilite de transistors performants. L'analyse des potentialites microondes sur la frequence de coupure du gain en courant de ces transistors revele que ces derniers s'ameliorent significativement avec la reduction de la longueur de grille et dans une moindre mesure avec l'abaissement de la temperature. L'absence d'evolution significative des capacites intrinseques avec la temperature confirme un bon confinement des porteurs dans le canal aux temperatures cryogeniques. Par ailleurs, la frequence maximale d'oscillation s'ameliore avec l'augmentation de la tension de drain, neanmoins l'utilisation des composants dans ces regimes de fonctionnement est limitee par la faible tenue au claquage des hemts sur inp. L'obtention de fortes densites de porteurs et des tensions de claquage elevees constituent les deux facteurs clef pour une montee en frequence encore plus importante. Les causes du claquage precoce de ces hemts sont etudiees de facon originale a partir de mesures d'electroluminescence. Celles-ci ont revele l'apparition d'un processus d'ionisation par choc dans le canal ingaas pour expliquer le claquage du composant. Par ailleurs, des anomalies ont ete observees sur les caracteristiques courant-tension. Ces anomalies sont la consequence de mecanismes de piegeage/depiegeage de porteurs dans les couches inalas et aux differentes interfaces. En conclusion, l'evolution des performances avec la temperature nous a permis de mieux comprendre les phenomenes physiques qui regissent le fonctionnement des hemts sur substrat inp a grille courte. L'etude a temperature variable s'est averee etre un outil precieux de caracterisation de l'ensemble de ces phenomenes
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(8999573), James R. Nakamura. "Electronic Fabry-Perot Interferometry of Quantum Hall Edge States." Thesis, 2020.
Find full textAbstract:
Two-dimensional electron systems in GaAs/AlGaAs heterostructures have provided a platform for investigating numerous phenomena in condensed matter physics. The quantum Hall effect is a particularly remarkable phenomenon due to its topological properties, including chiral edge states with quantized conductance. This report describes progress made in interference measurements of these edge states in electronic Fabry-Perot interferometers. Previous interference experiments in the quantum Hall regime have been stymied by Coulomb charging effects and poor quantum coherence. These Coulomb charging effects have been dramatically suppressed by the implementation of a novel GaAs/AlGaAs heterostructure which utilizes auxiliary screening wells in addition to the primary GaAs quantum well. Using this heterostructure, Aharonov-Bohm interference is measured in very small devices which have greatly improved coherence. Robust Aharonov-Bohm interference is reported at fractional quantum Hall states nu = 1/3 and nu = 2/3. Discrete jumps in phase at nu = 1/3 consistent with anyonic braiding statistics are observed. The report concludes with proposed future experiments, including extending these results to possible non-Abelian quantum Hall states.
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Rapp, Micah. "Visualizing cell surface interactions using cryogenic electron microscopy." Thesis, 2021. https://doi.org/10.7916/d8-5s5d-3s98.
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The study of the three-dimensional structures of biological macromolecules has given us significant insight into life and its mechanisms. Understanding these structures in their native contexts, a challenging but important goal, came closer to reality with the development of electron microscopy. After many years of technological development, we are now starting to understand previously intractable biological phenomena at an unprecedented resolution. One such phenomenon is how neighboring cells interact, both to communicate and send signals, and to adhere and form complex tissue structures. While the molecules that mediate such processes have long been studied in isolation, electron microscopy allows us to examine them in a more native biophysical environment; as hydrated, dynamic molecules tethered to opposed cellular membranes.Imaging unadulterated biological material using electron microscopy requires that the sample be embedded in a thin layer of vitreous ice to immobilize the molecules and protect them from the vacuum of the microscope, and thus is generally referred to as cryogenic electron microscopy (cryo-EM). Samples can be imaged using two common cryo-EM modalities: single particle analysis (SPA), where many two-dimensional projection images of molecules in solution are collected, and cryo-electron tomography (cryo-ET), where the sample is tilted as it is imaged at multiple angles to reconstruct a three-dimensional volume. In this work, I will describe how I have used both SPA and cryo-ET to understand cell surface interactions involving a variety of proteins.
The first chapter will look at the cell surface molecules known as the Toll receptors, a family of molecules found in Drosophila melanogaster, with orthologs in mammals known as the Toll-like receptors (TLRs). I will focus on their role in the development of the Drosophila embryo during germ band extension, a kind of convergent extension that is a conserved process through all metazoans. Biophysical assays of the three implicated Toll receptors, Toll-2, -6, and -8, revealed both homophilic and heterophilic interactions. SPA was used to determine the structure of monomeric Toll-2 which closely resembles the overall fold of Toll, whose structure was previously solved by x-ray crystallography. Surface plasmon resonance (SPR) spectroscopy and analytical ultracentrifugation (AUC) showed Toll-6 is a dimer in solution, which I visualized using cryo-EM. The Toll-6 homodimer is a novel dimer interface for Tolls and TLRs, where molecules on the same cell surface have been shown to dimerize in the presence of a wide variety of ligands. In contrast, the Toll-6 dimer is formed in the absence of any ligand and exists in an antiparallel arrangement that could be formed by molecules on opposing cell surfaces. Together, these results provide a biochemical basis for germ band extension which may be further explored through the study of structure-based mutations.
While cryo-EM SPA is a powerful tool, cryo-ET allows one to reconstruct three dimensional volumes of highly heterogeneous samples, such as the interior of cells, where molecules of interest may not exist in enough copies to facilitate averaging. This technique, where the sample is imaged multiple times as it is tilted to obtain three-dimensional information of a region of interest, was used to study cell adhesion of a different type: that mediated by the classical cadherins. These calcium-dependent adhesion molecules cluster into adherens junctions, spot-like protein densities found in a wide variety of tissues. In the second chapter, these junctions are recapitulated between synthetic liposome membranes by tethering the adherent cadherin molecules to chemically functionalized lipids. They are then imaged using cryo-ET to reveal higher-order structural details. First, this method is applied to the clustered protocadherins, a family of cadherins that mediate neuronal self-avoidance in mammals. Cryo-ET in combination with x-ray crystallography revealed that clustered protocadherins form extended one-dimensional zippers between membranes, which are a combination of strictly homophilic trans interactions coupled with promiscuous cis interactions. Neurons express unique subsets of the ~50-60 possible isoforms, and when two neuronal processes express identical subsets, which happens only when those processes are a part of the same cell, these linear chains grow and initiate a repulsive signal. If the subsets are different, the chains terminate and no repulsive signal is generated. The same technique has been used previously to study the type I classical cadherins, perhaps the most well-studied members of the cadherin superfamily. In the second half of this chapter, we extend our analysis to include the type II classical cadherins, which possess more complex expression patterns and binding specificities. Cryo-ET of type II cadherin ectodomains tethered to synthetic liposomes revealed that several representative members of this family form only moderately ordered arrays between liposomes, a finding in agreement with their role in cell sorting and migration. However, VE-cadherin, an outlier type II expressed in vascular endothelial cells where it withstands blood pressure, forms extraordinarily ordered junctions. Subtomogram averaging reveals the regularity of this two-dimensional array.
In the final chapter, I describe my work on a membrane surface molecule of a different kind, one not involved in cell adhesion but viral infection. The global COVID-19 pandemic gave me the opportunity to contribute to our understanding of SARS-CoV-2 by studying the structure of neutralizing antibodies bound to the viral spike protein, perhaps the most infamous membrane surface protein. The first subchapter describes the initial isolation, neutralization, and structural analysis of antibodies isolated from convalescent COVID-19 patients. This work revealed that patients with severe COVID-19 produce potently neutralizing antibodies that target two spike protein domains: the receptor binding domain (RBD) and the N-terminal domain (NTD). RBD-directed antibodies occlude binding to ACE2, the human receptor that mediates viral fusion, but the neutralization mechanism of NTD-directed antibodies is unknown. The following two subchapters are more detailed structural studies of two specific types of antibodies. The first looks at a class of RBD-directed antibodies derived from the VH1-2 gene, which are some of the most potent and common antibodies against SARS-CoV-2. The heavy chains of these antibodies recognize almost identical epitopes, but the antibodies employ a modular approach to recognize the RBD in either of its possible conformations. The second class are antibodies that target the NTD, which our work revealed all bind to a single antigenic supersite. The final subchapter focuses on emerging SARS-CoV-2 variants and includes the structures of two antibodies that are still capable of neutralizing these new variants. They are also infrequent in the human antibody response to SARS-CoV-2, meaning they put little selective pressure on the virus to produce escape mutations, making them good candidates for monoclonal antibody therapies.
Though Drosophila embryogenesis, adherens junction formation, and SARS-CoV-2 neutralization are seemingly unrelated systems, they are united by the incredible flexibility of cryo-EM to visualize biological molecules in more native environments. Whether it is the ability to study multiprotein complexes or assemblies formed between membranes, cryo-EM is a powerful technique that promises to help bridge the divide between structure and function.
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Tan, Yong Zi. "Solving Challenging Structures using Single-Particle Cryogenic Electron Microscopy." Thesis, 2019. https://doi.org/10.7916/d8-czh4-ry10.
Full textAbstract:
Single-particle cryogenic electron microscopy (cryo-EM) has become a powerful mainstay tool in high resolution structural biology thanks to advances in hardware, software and sample preparation technology. In my thesis, I utilized this technique to unravel the function of various challenging biological macromolecules.
My first focus was bacterial ribosomal biogenesis: understanding how bacteria assemble their ribosomes. Ribosomes are the factories of the cell, responsible for manufacturing all proteins. Ribosomes themselves are huge, with the bacterial version made of 52 proteins and 4566 RNA nucleotides. How these components assemble has long been a mystery. Early groundbreaking work sketched out a biogenesis pathway using purified components in vitro – but under non-physiological conditions. We sought to understand how the bacterial ribosome – specifically the large subunit 50S – is built inside the cell. To achieve this, we engineered a conditional knock-out bacterial strain that lacked one specific ribosomal protein (L17). This caused the cells to accumulate incomplete intermediates along the 50S biogenesis pathway. These intermediates were purified and examined with mass spectrometry and single-particle cryo-EM.
Two major hurdles arose in this project: firstly, the biogenesis intermediates exhibited a preferred orientation when vitrified for cryo-EM analysis. This means that instead of showing many different views required for reconstruction of the 3D structure, the intermediates only adopted one view on the cryo-EM grid. To overcome this problem, we engineered a method to induce additional views on the microscope by tilting the stage. Using another test protein that also exhibited preferred orientation (hemagglutinin), we optimized and characterized this new tilt methodology and showed it was generally applicable to overcoming preferred orientation, regardless of type of specimen. We also created a software tool, called 3DFSC (3dfsc.salk.edu), for other microscopists to calculate the degree of directional anisotropy in their structures due to preferred orientation. Using this tilt strategy finally enabled the structural elucidation of our 50S intermediates. The second challenge in the project was the large amount of heterogeneity present in the sample. Through hierarchical 3D classification schemes using the latest software tools, we obtained 14 different 50S intermediate structures, all from imaging a single cryo-EM grid. By analyzing the missing components of each intermediate, and corroborating these observations with mass spectrometry data, we outlined the first in vivo 50S assembly pathway, and showed that ribosome assembly occurs step-wise and in parallel pathways.
My second focus was on pushing the resolution limits of single-particle cryo-EM using adeno-associated virus (AAV) serotype 2 homogeneous virus-like particles (VLPs) that lack DNA. Exploiting several technical advances to improve resolution, including use of gold grids, per-particle CTF refinement, and correction for Ewald sphere curvature, we managed to obtain a 1.86 Å resolution reconstruction of the AAV2L336C variant VLP, the highest resolution icosahedral virus reconstruction solved by single-particle cryo-EM to date. Using our structure, we were able to show improvements using Ewald sphere curvature correction and shed light on the mechanistic basis as to why the L336C mutation resulted in defects in genome packaging and infectivity compared to the WT viral particles.
My third focus was the understanding of small membrane proteins involved in infectious diseases. Membrane proteins are a challenge to work with due to the need for them to be extracted from the lipid bilayer for studies as compared to soluble proteins. Infectious diseases have a huge burden on society, with the top three infectious agents accounting for 2.7 million deaths in 2016. The third most deadly infectious disease is malaria, a mosquito-borne parasite which kills 450,000 people annually. One drug used early on for treating malaria was chloroquine but its usefulness waned due to development of resistance. Chloroquine resistance is mediated by the chloroquine resistance transporter (PfCRT). Although small (49 kDa) for single-particle cryo-EM, we solved its structure by using fragment antibody technology to add mass and help with image alignment and 3D reconstruction. The 3.2 Å structure resembles other drug metabolite transporters, and the chloroquine resistance mutations map to a ring around the central cavity, suggesting this central pore as the drug binding site.
Tuberculosis (TB) is the top killer, above malaria and HIV/AIDS, being responsible for 1.3 million deaths. In TB, a common antibiotic target is the bacterium’s cell wall synthesis machinery. One family of such enzymes is the arabinosyltransferases, which synthesize the critical arabinose sugars. Using single-particle cryo-EM, we solved two high resolution structures of one such essential enzyme, AftD. Due to the low yield of the protein, a picoliter automated sample dispensing robot was crucial to allow for initial cryo-EM analysis. We then performed mutagenesis studies in M. smegmatis, a TB model organism, which uncovered the critical amino acid residues in the active site and determined that a bound acyl-carrier-protein was likely involved in allosteric inhibition of AftD’s active site. Another member of the family, EmbB, is the target of a widely used frontline TB drug called ethambutol. We have solved the high resolution structures of the apo and putative drug-bound states of EmbB, allowing us to map out, for the first time, both the active site and drug-resistance mutations of this crucial enzyme. The atomic structures of the functional pockets of Mycobacterial AftD and malarial PfCRT will hopefully enable structure-based drug design to improve existing drugs or potentially even develop new treatments against these infectious maladies.
In conclusion, the continual and breathtaking improvements in single-particle cryo-EM methodology has been instrumental in allowing the elucidation of the aforementioned biological macromolecules from ribosome biogenesis intermediates, to AAV2 vehicle, Plasmodium drug resistance transporter to mycobacterial glycosyltransferases – structures of which help explain biological function.