Academic literature on the topic 'Switching kinetics'

DNA polymerase epsilon (Pol ε) is a multi-subunit B-family DNA polymerase that is involved in leading strand DNA replication in eukaryotes. DNA Pol ε in yeast consists of four subunits, Pol2, Dpb2, Dpb3, and Dpb4. Pol2 is the catalytic subunit and Dpb2, Dpb3, and Dpb4 are the accessory subunits. Pol2 can be further divided into an N-terminal catalytic core (Pol2core) containing both the polymerase and exonuclease active sites and a C-terminus domain. We determined the X-ray crystal structure of Pol2core at 2.2 Å bound to DNA and with an incoming dATP. Pol ε has typical fingers, palm, thumb, exonuclease, and N-terminal domains in common with all other B-family DNA polymerases. However, we also identified a seemingly novel domain we named the P-domain that only appears to be present in Pol ε. This domain partially encircles the nascent duplex DNA as it leaves the active site and contributes to the high intrinsic processivity of Pol ε. To ask if the crystal structure of Pol2core can serve as a model for catalysis by Pol ε, we investigated how the C-terminus of Pol2 and the accessory subunits of Pol ε influence the enzymatic mechanism by which Pol ε builds new DNA efficiently and with high fidelity. Pre-steady state kinetics revealed that the exonuclease and polymerization rates were comparable between Pol2core and Pol ε. However, a global fit of the data over five nucleotide-incorporation events revealed that Pol ε is slightly more processive than Pol2 core. The largest differences were observed when measuring the time for loading the polymerase onto a 3' primer-terminus and the subsequent incorporation of one nucleotide. We found that Pol ε needed less than a second to incorporate the first nucleotide, but it took several seconds for Pol2core to incorporate similar amounts of the first nucleotide. B-family polymerases have evolved an extended β-hairpin loop that is important for switching the primer terminus between the polymerase and exonuclease active sites. The high-resolution structure of Pol2core revealed that Pol ε does not possess an extended β-hairpin loop. Here, we show that Pol ε can processively transfer a mismatched 3' primer-terminus between the polymerase and exonuclease active sites despite the absence of a β-hairpin loop. Additionally we have characterized a series of amino acid substitutions in Pol ε that lead to altered partitioning of the 3'primer-terminus between the two active sites. In a final set of experiments, we investigated the ability of Pol ε to displace the downstream double-stranded DNA while carrying out DNA synthesis. Pol ε displaced only one base pair when encountering double-stranded DNA after filling a gap or a nick. However, exonuclease deficient Pol ε carries out robust strand displacement synthesis and can reach the end of the templates tested here. Similarly, an abasic site or a ribonucleotide on the 5'-end of the downstream primer was efficiently displaced but still only by one nucleotide. However, a flap on the 5'-end of the blocking primer resembling a D-loop inhibited Pol ε before it could reach the double-stranded junction. Our results are in agreement with the possible involvement of Pol ε in short-patch base excision repair and ribonucleotide excision repair but not in D-loop extension or long-patch base excision repair.

Wireless micro-sensors can enjoy popularity in biomedical drug-delivery treatments and tire-pressure monitoring systems because they offer in-situ, real-time, non-intrusive processing capabilities. However, miniaturized platforms severely limit the energy of onboard batteries and shorten the lifespan of electronic systems. Ambient energy is an attractive alternative because the energy from light, heat, radio-frequency (RF) radiation, and motion can potentially be used to continuously replenish an exhaustible reservoir. Of these sources, solar light produces the highest power density, except when supplied from indoor lighting, under which conditions the available power decreases drastically. Harnessing thermal energy is viable, but micro-scale dimensions severely limit temperature gradients, the fundamental mechanism from which thermo piles draw power. Mobile electronic devices today radiate plenty of RF energy, but still, the available power rapidly drops with distance. Harvesting kinetic energy may not compete with solar power, but in contrast to indoor lighting, thermal, and RF sources, moderate and consistent vibration power across a vast range of applications is typical. Although operating conditions ultimately determine which kinetic energy-harvesting method is optimal, piezoelectric transducers are relatively mature and produce comparatively more power than their counterparts such as electrostatic and electromagnetic kinetic energy transducers. The presented research objective is to develop, design, simulate, fabricate, prototype, test, and evaluate CMOS ICs that harvest ambient kinetic energy in periodic and non-periodic vibrations using a small piezoelectric transducer to continually replenish an energy-storage device like a capacitor or a rechargeable battery. Although vibrations in surrounding environment produce abundant energy over time, tiny transducers can harness only limited power from the energy sources, especially when mechanical stimulation is weak. To overcome this challenge, the presented piezoelectric harvesters eliminate the need for a rectifier which necessarily imposes threshold limits and additional losses in the system. More fundamentally, the presented harvesting circuits condition the transducer to convert more electrical energy for a given mechanical input by increasing the electromechanical damping force of the piezoelectric transducer. The overall aim is to acquire more power by widening the input range and improving the efficiency of the IC as well as the transducer. The presented technique in essence augments the energy density of micro-scale electronic systems by scavenging the ambient kinetic energy and extends their operational lifetime. This dissertation reports the findings acquired throughout the investigation. The first chapter introduces the applications and challenges of micro-scale energy harvesting and also reviews the fundamental mechanisms and recent developments of various energy-converting transducers that can harness ambient energy in light, heat, RF radiation, and vibrations. Chapter 2 examines various existing piezoelectric harvesting circuits, which mostly adopt bridge rectifiers as their core. Chapter 3 then introduces a bridge-free piezoelectric harvester circuit that employs a switched-inductor power stage to eliminate the need for a bridge rectifier and its drawbacks. More importantly, the harvester strengthens the electrical damping force of the piezoelectric device and increases the output power of the harvester. The chapter also presents the details of the integrated-circuit (IC) implementation and the experimental results of the prototyped harvester to corroborate and clarify the bridge-free harvester operation. One of the major discoveries from the first harvester prototype is the fact that the harvester circuit can condition the piezoelectric transducer to strengthen its electrical damping force and increase the output power of the harvester. As such, Chapter 4 discusses various energy-investment strategies that increase the electrical damping force of the transducer. The chapter presents, evaluates, and compares several switched-inductor harvester circuits against each other. Based on the investigation in Chapter 4, an energy-investing piezoelectric harvester was designed and experimentally evaluated to confirm the effectiveness of the investing scheme. Chapter 5 explains the details of the IC design and the measurement results of the prototyped energy-investing piezoelectric harvester. Finally, Chapter 6 concludes the dissertation by revisiting the challenges of miniaturized piezoelectric energy harvesters and by summarizing the fundamental contributions of the research. With the same importance as with the achievements of the investigation, the last chapter lists the technological limits that bound the performance of the proposed harvesters and briefly presents perspectives from the other side of the research boundary for future investigations of micro-scale piezoelectric energy harvesting.

In dieser Arbeit werden die Auswirkungen epitaktischer Dehnung auf die Eigenschaften ferromagnetischer und ferroelektrischer Perowskitschichten untersucht. Dazu wird der biaxiale Dehnungszustand einer Schicht reversibel verändert, indem einkristalline piezoelektrische Pb(Mg1/3Nb2/3)0.72Ti0.28O3 (001) Substrate (PMN-PT) verwendet werden. Ergänzt werden die Messungen mit dieser “dynamischen” Methode durch Untersuchungen an statisch gedehnten Schichten, gewachsen auf LaAlxSc1-xO3-Pufferschichten mit gezielt abgestimmter Gitterfehlpassung. Drei verschiedene Materialsysteme werden studiert: die ferromagnetischen Oxide La0.8Sr0.2CoO3 und SrRuO3 und das ferroelektrische Pb(Zr,Ti)O3. Für La0.8Sr0.2CoO3 wird ein dehnungsinduzierter Übergang von der bekannten ferromagnetischen Phase zu einer magnetisch weniger geordneten, spinglasartigen Phase nachgewiesen. Es ergeben sich keine Hinweise auf eine Beeinflussung des Co-Spinzustandes. In epitaktischen SrRuO3-Schichten bewirkt eine Zugdehnung einen strukturellen Phasenübergang von der orthorhombischen Bulk-Phase zu einer out-of-plane orientierten tetragonalen Phase. Die leichte Richtung liegt in der Ebene. Reversible Dehnungsmessungen zeigen einen deutlichen Einfluss auf die ferromagnetische Ordnungstemperatur und deuten auf eine geringe Veränderung des magnetischen Moments hin. Der Dehnungseffekt auf die elektrischen Transporteigenschaften wird bestimmt. Pb(Zr,Ti)O3 wird als ferroelektrisches Standardmaterial genutzt, um erstmalig den Einfluss biaxialer Dehnung auf das ferroelektrische Schaltverhalten dünner Schichten zu untersuchen. Für kleine elektrische Felder zeigen die Messungen das typische Verhalten einer gepinnten Domänenwandbewegung. Hier wird der Schaltvorgang unter Piezokompression stark beschleunigt. Werden an die elektrischen Kontakte größere elektrische Felder angelegt, geht die Domänenwandbewegung in das Depinning-Regime über. Die Schaltkinetik wird in diesem Bereich unter Piezokompression leicht verlangsamt<br>In this work, the effect of epitaxial strain on the properties of ferromagnetic and ferroelectric perovskite thin films is studied. Single-crystalline piezoelectric Pb(Mg1/3Nb2/3)0.72Ti0.28O3 (001) substrates (PMN-PT) are utilized to reversibly change the biaxial strain state of the films. The measurements performed by this “dynamic” approach are complemented by studying statically strained films grown on LaAlxSc1-xO3 buffer layers with deliberately tuned lattice misfit. Three different material systems are investigated: the ferromagnetic oxides La0.8Sr0.2CoO3 and SrRuO3 and the ferroelectric compound Pb(Zr,Ti)O3. In case of La0.8Sr0.2CoO3 a strain-induced transition from the known ferromagnetic phase to a magnetically less ordered spinglas-like phase is observed. No indications for an effect on the Co spin state are found. In epitaxial SrRuO3 films tensile strain is causing a structural phase transition from the bulk-like orthorhombic structure to an out-of-plane oriented tetragonal phase. The magnetic easy axis is in the film plane. Reversible strain experiments show a significant effect on the ferromagnetic ordering temperature and point to a small change of the magnetic moment. The strain effect on the electric transport properties is also determined. Pb(Zr,Ti)O3 as a standard ferroelectric material is used to study the influence of biaxial strain on the ferroelectric switching behaviour of thin films for the first time. At small electric fields the measurements reveal the typical signs of creep-like domain wall motion caused by wall pinning. In this regime the switching process is accelerated strongly under piezo-compression. For higher electric fields a transition of the domain wall motion to the depinning regime is observed. Here, the switching kinetics is slowed down moderately by compressive strain

Proteins are involved in numerous functions in the human body, including chemical transport, molecular recognition, and catalysis. To perform their function most proteins must adopt a specific structure (often referred to as the folded structure). A microscopic description of folding is an important prerequisite for elucidating the underlying basis of protein misfolding and rational drug design. However, protein folding occurs on heterogeneous length and time scales, presenting a grand challenge to both experiments and simulations. In computer simulations, challenges are generally mitigated by adopting coarse-grained descriptions of the physical environment, employing enhanced sampling strategies, and improving computing code and hardware. While significant advances have been made in these areas, for numerous systems a large spatiotemporal gap between experiment and simulations still exists, due to the limited time and length scales achieved by simulation, and the inability of many experimental techniques to probe fast motions and short distances. In this thesis, kinetic transition networks (KTNs) are constructed for various protein folding systems, via approaches based on the potential energy landscape (PEL) framework. By applying geometry optimisation techniques, the PEL is discretised into stationary points (i.e.~low-energy minima and the transition states that connect them). Essentially, minima characterise the low-lying regions of the PEL (thermodynamics) and transition states encode the motion between these regions (dynamics). Principles from statistical mechanics and unimolecular rate theory may then be employed to derive free energy surfaces and folding rates, respectively, from the KTN. Furthermore, the PEL framework can take advantage of parallel and distributed computing, since stationary points from separate simulations can be easily integrated into one KTN. Moreover, the use of geometry optimisation facilitates greater conformational sampling than conventional techniques based on molecular dynamics. Accordingly, this framework presents an appealing means of probing complex processes, such as protein folding. In this dissertation, we demonstrate the application of state-of-the-art theory, combining PEL analysis and KTNs to three diverse protein systems. First, to improve the efficiency of protein folding simulations, the intrinsic rigidity of proteins is exploited by implementing a local rigid body (LRB) approach. The LRB approach effectively integrates out irrelevant degrees of freedom from the geometry optimisation procedure and further accelerates conformational sampling. The effects of this approach on the underlying PEL are analysed in a systematic fashion for a model protein (tryptophan zipper\,1). We demonstrate that conservative local rigidification can reproduce the thermodynamic and dynamic properties for the model protein. Next, the PEL framework is employed to model large-scale conformational changes in proteins, which have conventionally been difficult to probe in silico. Methods based on geometry optimisation have proved useful in overcoming the broken ergodicity issue, which is associated with proteins that switch morphology. The latest PEL-based approaches are utilised to investigate the most extreme case of fold-switching found in the literature:~the α-helical hairpin to β-barrel transition of the C-terminal domain of RfaH, a bacterial transcription factor. PEL techniques are employed to construct the free energy landscape (FEL) for the refolding process and to discover mechanistic details of the transition at an atomistic level. The final part of the thesis focuses on modelling intrinsically disordered proteins (IDPs). Due to their inherent structural plasticity, IDPs are generally difficult to characterise, both experimentally and via simulations. An approach for studying IDPs within the PEL framework is implemented and tested with various contemporary potential energy functions. The cytoplasmic tail of the human cluster of differentiation 4 (CD4), implicated in HIV-1 infection, is characterised. Metastable states identified on the FEL help to unify, and are consistent with, several earlier predictions.

The classical Kolmogorov-Avrami-Ishibashi (KAI) model successfully describes polarization switching kinetics of single crystals. Later on, Tagantsev et al. introduced a statistical distribution of switching time (SwT) in the KAI model; the improved statistical model is known as the nucleation limited switching (NLS) model and became suitable for thin films. Based on a robust dependence of SwT on an electric field, Lupascu et al. have proposed that the nature of the SwT statistical distribution can be attributed to a corresponding distribution of local electric fields inside a material. Using this assumption, the inhomogeneous field mechanism (IFM) model was developed. Although the NLS and IFM models are able to describe experimental measurements with high accuracy they neglect several crucial physical aspects of the poling problem. A disordered granular structure in a polarized state is unavoidably accompanied by charge formation on grain boundaries (GB), therefore giving rise to additional electric fields. Charges on grain boundaries should vary depending on polarization, therefore depolarization fields should be also time dependent. The latter fact, however, is omitted in the NLS as well as in the IFM models. Another questionable assumption, included in all statistical models, is the statistical independence of switching regions, which is doubtful since the huge depolarization fields have to produce grain correlations. Statistical independence of switching events disable accounting for non-180 switching events because these events are sequential processes rather than independent. Hence an independent switching mechanism is not suitable for this process. These all make the aforementioned statistical models and the reliability of extracted parameters questionable. This work aims to shed some light on the reliability of statistical models by investigation of charge formation on grain boundaries during a poling process as well as produced depolarization fields and their evolution. Correlations of polarization and electric field components are analyzed. All studies are carried out for tetragonal, rhombohedral and orthorhombic symmetries and are in good agreement with previous theoretical results and experimental measurements. A new statistical model which involves non-180 switching events is presented and successfully applied to the recent polarization-time and strain-time measurements. A statistical distribution of electric fields is additionally studied for the case of porous ceramics as they are materials where the distribution can be controlled by modifications to the structure.

The complex domain structure in ferroelectrics gives rise to electromechanical coupling, and its evolution (via domain switching) results in a time-dependent (i.e. viscoelastic) response. Although ferroelectrics are used in many technological applications, most do not attempt to exploit the viscoelastic response of ferroelectrics, mainly due to a lack of understanding and accurate models for their description and prediction. Thus, the aim of this thesis research is to gain better understanding of the influence of domain evolution in ferroelectrics on their dynamic mechanical response. There have been few studies on the viscoelastic properties of ferroelectrics, mainly due to a lack of experimental methods. Therefore, an apparatus and method called Broadband Electromechanical Spectroscopy (BES) was designed and built. BES allows for the simultaneous application of dynamic mechanical and electrical loading in a vacuum environment. Using BES, the dynamic stiffness and loss tangent in bending and torsion of a particular ferroelectric, viz. lead zirconate titanate (PZT), was characterized for different combinations of electrical and mechanical loading frequencies throughout the entire electric displacement hysteresis. Experimental results showed significant increases in loss tangent (by nearly an order of magnitude) and compliance during domain switching, which shows promise as a new approach to structural damping. A continuum model of the viscoelasticity of ferroelectrics was developed, which incorporates microstructural evolution via internal variables and associated kinetic relations. For the first time, through a new linearization process, the incremental dynamic stiffness and loss tangent of materials were computed throughout the entire electric displacement hysteresis for different combinations of mechanical and electrical loading frequencies. The model accurately captured experimental results. Using the understanding gained from the characterization and modeling of PZT, two applications of domain switching kinetics were explored by using Micro Fiber Composites (MFCs). Proofs of concept of set-and-hold actuation and structural damping using MFCs were demonstrated.