Expanding the PET radioisotope universe utilizing solid targets on small medical cyclotrons.

Molecular imaging with medical radioisotopes enables the minimally-invasive monitoring of aberrant biochemical, cellular and tissue-level processes in living subjects. The approach requires the administration of radiotracers composed of radioisotopes attached to bioactive molecules, the pairing of which considers several aspects of the radioisotope in addition to the biological behavior of the targeting molecule to which it is attached. With the advent of modern cellular and biochemical techniques, there has been a virtual explosion in potential disease recognition antigens as well as targeting moieties, which has subsequently opened new applications for a host of emerging radioisotopes with well-matched properties. Additionally, the global radioisotope production landscape has changed rapidly, with reactor-based production and its long-defined, large-scale centralized manufacturing and distribution paradigm shifting to include the manufacture and distribution of many radioisotopes via a worldwide fleet of cyclotrons now in operation. Cyclotron-based radioisotope production has become more prevalent given the commercial availability of instruments, coupled with the introduction of new target hardware, process automation and target manufacturing methods. These advances enable sustained, higher-power irradiation of solid targets that allow hospital-based radiopharmacies to produce a suite of radioisotopes that drive research, clinical trials, and ultimately clinical care. Over the years, several different radioisotopes have been investigated and/or selected for radiolabeling due to favorable decay characteristics (i.e. a suitable half-life, high probability of positron decay, etc.), well-elucidated chemistry, and a feasible production framework. However, longer-lived radioisotopes have surged in popularity given recent regulatory approvals and incorporation of radiopharmaceuticals into patient management within the medical community. This review focuses on the applications, nuclear properties, and production and purification methods for some of the most frequently used/emerging positron-emitting, solid-target-produced radioisotopes that can be manufactured using small-to-medium size cyclotrons (≤24 MeV).

Exotic states in a simple network of nanoelectromechanical oscillators.

Synchronization of oscillators, a phenomenon found in a wide variety of natural and engineered systems, is typically understood through a reduction to a first-order phase model with simplified dynamics. Here, by exploiting the precision and flexibility of nanoelectromechanical systems, we examined the dynamics of a ring of quasi-sinusoidal oscillators at and beyond first order. Beyond first order, we found exotic states of synchronization with highly complex dynamics, including weak chimeras, decoupled states, traveling waves, and inhomogeneous synchronized states. Through theory and experiment, we show that these exotic states rely on complex interactions emerging out of networks with simple linear nearest-neighbor coupling. This work provides insight into the dynamical richness of complex systems with weak nonlinearities and local interactions.

Minimum-action paths for wave-number selection in nonequilibrium systems.

The problem of wave-number selections in nonequilibrium pattern-forming systems in the presence of noise is investigated. The minimum-action method is proposed to study the noise-induced transitions between the different spatiotemporal states by generalizing the traditional theory previously applied in low-dimensional dynamical systems. The scheme is shown as an example in the stabilized Kuramoto-Sivashinsky equation. The present method allows us to conveniently find the unique noise selected state, in contrast to previous work using direct simulations of the stochastic partial differential equation, where the constraints of the simulation only allow a narrow band to be determined.

Eliminating 1/f noise in oscillators.

We study 1/f and narrow-bandwidth noise in precision oscillators based on high-quality factor resonators and feedback. The dynamics of such an oscillator are well described by two variables, an amplitude and a phase. In this description we show that low-frequency feedback noise is represented by a single noise vector in phase space. The implication of this is that 1/f and narrow-bandwidth noise can be eliminated by tuning controllable parameters, such as the feedback phase. We present parameter values for which the noise is eliminated and provide specific examples of noise sources for further illustration.

Phase synchronization of two anharmonic nanomechanical oscillators.

We investigate the synchronization of oscillators based on anharmonic nanoelectromechanical resonators. Our experimental implementation allows unprecedented observation and control of parameters governing the dynamics of synchronization. We find close quantitative agreement between experimental data and theory describing reactively coupled Duffing resonators with fully saturated feedback gain. In the synchronized state we demonstrate a significant reduction in the phase noise of the oscillators, which is key for sensor and clock applications. Our work establishes that oscillator networks constructed from nanomechanical resonators form an ideal laboratory to study synchronization--given their high-quality factors, small footprint, and ease of cointegration with modern electronic signal processing technologies.

Coupled motion of microscale and nanoscale elastic objects in a viscous fluid.

We study the coupled dynamics of two closely spaced micron or nanoscale elastic objects immersed in a viscous fluid. The dynamics of the elastic objects are coupled through the motion of the surrounding viscous fluid. We consider two cases: (i) one object is driven externally by an imposed harmonic actuation force and the second object is passive and (ii) both objects are driven by a Brownian force to yield stochastic dynamics. Using a harmonic oscillator approximation for the elastic objects and the unsteady Stokes equations to describe the fluid dynamics, we develop analytical expressions for the amplitude and phase of the displacement of the oscillating objects. For the case of an imposed actuation we use an impulse in force to determine the resulting dynamics over all frequencies. For the Brownian-driven objects the stochastic dynamics are found using the fluctuation-dissipation theorem. We validate our theoretical expressions by comparison with results from finite-element numerical simulations of the complete fluid-solid interaction problem. Our results yield interesting features in the amplitude and phase of the displacement of the elastic objects due to the fluid motion. We find that the dynamics depend on the separation of the objects, a measure of the mass loading due to the fluid, and the frequency parameter which acts as a frequency-based Reynolds number. Our results are valid over the range of parameters typical of micron and nanoscale elastic objects in fluid. The range of dynamics found can be understood in terms of the interplay between the viscous and potential components of the fluid flow field described by the unsteady Stokes equation for an oscillating cylinder. For small values of the frequency parameter, typical of nanoscale elastic objects, the dynamics are overdamped due to the dominance of viscous forces over inertial forces. For moderate and large values of the frequency parameter, typical of micron-scale elastic objects, we find that the dynamics of the fluid-coupled objects exhibits an interesting mode splitting to yield a bimodal signature in the amplitude-frequency plots. We find that the mode splitting can be described using a normal mode analysis containing only potential fluid interactions between the cylinders.

Frequency precision of two-dimensional lattices of coupled oscillators with spiral patterns.

Two-dimensional lattices of N synchronized oscillators with reactive coupling are considered as high-precision frequency sources in the case where a spiral pattern is formed. The improvement of the frequency precision is shown to be independent of N for large N, unlike the case of purely dissipative coupling where the improvement is proportional to N, but instead depends on just those oscillators in the core of the spiral that acts as the source region of the waves. Our conclusions are based on numerical simulations of up to N=29929 oscillators and analytic results for a continuum approximation to the lattice in an infinite system. We derive an expression for the dependence of the frequency precision on the reactive component of the coupling constant, depending on a single parameter given by fitting the frequency of the spiral waves to the numerical simulations.

Surpassing fundamental limits of oscillators using nonlinear resonators.

In its most basic form an oscillator consists of a resonator driven on resonance, through feedback, to create a periodic signal sustained by a static energy source. The generation of a stable frequency, the basic function of oscillators, is typically achieved by increasing the amplitude of motion of the resonator while remaining within its linear, harmonic regime. Contrary to this conventional paradigm, in this Letter we show that by operating the oscillator at special points in the resonator's anharmonic regime we can overcome fundamental limitations of oscillator performance due to thermodynamic noise as well as practical limitations due to noise from the sustaining circuit. We develop a comprehensive model that accounts for the major contributions to the phase noise of the nonlinear oscillator. Using a nanoelectromechanical system based oscillator, we experimentally verify the existence of a special region in the operational parameter space that enables suppressing the most significant contributions to the oscillator's phase noise, as predicted by our model.

Phase noise of oscillators with unsaturated amplifiers.

We study the role of amplifier saturation in eliminating feedback noise in self-sustained oscillators. We extend previous works that use a saturated amplifier to quench fluctuations in the feedback magnitude, while simultaneously tuning the oscillator to an operating point at which the resonator nonlinearity cancels fluctuations in the feedback phase. We consider a generalized model which features an amplitude-dependent amplifier gain function. This allows us to determine the total oscillator phase noise in realistic configurations due to noise in both quadratures of the feedback, and to show that it is not necessary to drive the resonator to large oscillation amplitudes in order to eliminate noise in the phase of the feedback.

Optimal operating points of oscillators using nonlinear resonators.

We demonstrate an analytical method for calculating the phase sensitivity of a class of oscillators whose phase does not affect the time evolution of the other dynamic variables. We show that such oscillators possess the possibility for complete phase noise elimination. We apply the method to a feedback oscillator which employs a high Q weakly nonlinear resonator and provide explicit parameter values for which the feedback phase noise is completely eliminated and others for which there is no amplitude-phase noise conversion. We then establish an operational mode of the oscillator which optimizes its performance by diminishing the feedback noise in both quadratures, thermal noise, and quality factor fluctuations. We also study the spectrum of the oscillator and provide specific results for the case of 1/f noise sources.

Passive phase noise cancellation scheme.

We introduce a new method for reducing phase noise in oscillators, thereby improving their frequency precision. The noise reduction is realized by a passive device consisting of a pair of coupled nonlinear resonating elements that are driven parametrically by the output of a conventional oscillator at a frequency close to the sum of the linear mode frequencies. Above the threshold for parametric instability, the coupled resonators exhibit self-oscillations which arise as a response to the parametric driving, rather than by application of active feedback. We find operating points of the device for which this periodic signal is immune to frequency noise in the driving oscillator, providing a way to clean its phase noise. We present results for the effect of thermal noise to advance a broader understanding of the overall noise sensitivity and the fundamental operating limits.

Improving the frequency precision of oscillators by synchronization.

Improving the frequency precision by synchronizing a lattice of N oscillators with disparate frequencies is studied in the phase reduction limit. In the general case where the coupling is not purely dissipative the synchronized state consists of targetlike waves radiating from a local source, which is a region of higher-frequency oscillators. In this state the improvement of the frequency precision is shown to be independent of N for large N, but instead depends on the disorder and reflects the dependence of the frequency of the synchronized state on just those oscillators in the source region of the waves. These results are obtained by a mapping of the nonlinear phase dynamics onto the linear Anderson problem of the quantum mechanics of electrons on a random lattice in the tight-binding approximation.

Quasiperiodic, periodic, and slowing-down states of coupled heteroclinic cycles.

We investigate two coupled oscillators, each of which shows an attracting heteroclinic cycle in the absence of coupling. The two heteroclinic cycles are nonidentical. Weak coupling can lead to the elimination of the slowing-down state that asymptotically approaches the heteroclinic cycle for a single cycle, giving rise to either quasiperiodic motion with separate frequencies from the two cycles or periodic motion in which the two cycles are synchronized. The synchronization transition, which occurs via a Hopf bifurcation, is not induced by the commensurability of the two cycle frequencies but rather by the disappearance of the weaker frequency oscillation. For even larger coupling the motion changes via a resonant heteroclinic bifurcation to a slowing-down state corresponding to a single attracting heteroclinic orbit. Coexistence of multiple attractors can be found for some parameter regions. These results are of interest in ecological, sociological, neuronal, and other dynamical systems, which have the structure of coupled heteroclinic cycles.

Collective quantum jumps of Rydberg atoms.

We study an open quantum system of atoms with a long-range Rydberg interaction, laser driving, and spontaneous emission. Over time, the system occasionally jumps between a state of low Rydberg population and a state of high Rydberg population. The jumps are inherently collective, and in fact, exist only for a large number of atoms. We explain how entanglement and quantum measurement enable the jumps, which are otherwise classically forbidden.

Pattern formation with trapped ions.

Ion traps are a versatile tool to study nonequilibrium statistical physics, due to the tunability of dissipation and nonlinearity. We propose an experiment with a chain of ions, where dissipation is provided by laser heating and cooling, while nonlinearity is provided by trap anharmonicity and beam shaping. The dynamics are governed by an equation similar to the complex Ginzburg-Landau equation, except that the reactive nature of the coupling leads to qualitatively different behavior. The system has the unusual feature of being both oscillatory and excitable at the same time. The patterns are observable for realistic experimental parameters despite noise from spontaneous emission. Our scheme also allows controllable experiments with noise and quenched disorder.

Signal amplification by sensitive control of bifurcation topology.

We describe a novel amplification scheme based on inducing dynamical changes to the topology of a bifurcation diagram of a simple nonlinear dynamical system. We have implemented a first bifurcation-topology amplifier using a coupled pair of parametrically driven high-frequency nanoelectromechanical systems resonators, demonstrating robust small-signal amplification. The principles that underlie bifurcation-topology amplification are simple and generic, suggesting its applicability to a wide variety of physical, chemical, and biological systems.

Synchronization of oscillators with long-range power law interactions.

We present analytical calculations and numerical simulations for the synchronization of oscillators interacting via a long-range power law interaction on a one-dimensional lattice. We have identified the critical value of the power law exponent α(c) across which a transition from a synchronized to an unsynchronized state takes place for a sufficiently strong but finite coupling strength in the large system limit. We find α(c)=3/2. Frequency entrainment and phase ordering are discussed as a function of α≥1 . The calculations are performed using an expansion about the aligned phase state (spin-wave approximation) and a coarse graining approach. We also generalize the spin-wave results to the d -dimensional problem.

Vortices and the entrainment transition in the two-dimensional Kuramoto model.

We study synchronization in the two-dimensional lattice of coupled phase oscillators with random intrinsic frequencies. When the coupling K is larger than a threshold K{E} , there is a macroscopic cluster of frequency-synchronized oscillators. We explain why the macroscopic cluster disappears at K{E} . We view the system in terms of vortices, since cluster boundaries are delineated by the motion of these topological defects. In the entrained phase (K>K{E}) , vortices move in fixed paths around clusters, while in the unentrained phase (K

Renormalization group approach to oscillator synchronization.

We develop a renormalization group method to investigate synchronization clusters in a one-dimensional chain of nearest-neighbor coupled phase oscillators. The method is best suited for chains with strong disorder in the intrinsic frequencies and coupling strengths. The results are compared with numerical simulations of the chain dynamics and good agreement in several characteristics is found. We apply the renormalization group and simulations to Lorentzian distributions of intrinsic frequencies and couplings and investigate the statistics of the resultant cluster sizes and frequencies, as well as the dependence of the characteristic cluster length upon parameters of these Lorentzian distributions.

Intrinsic localized modes in parametrically driven arrays of nonlinear resonators.

We study intrinsic localized modes (ILMs), or solitons, in arrays of parametrically driven nonlinear resonators with application to microelectromechanical and nanoelectromechanical systems (MEMS and NEMS). The analysis is performed using an amplitude equation in the form of a nonlinear Schrödinger equation with a term corresponding to nonlinear damping (also known as a forced complex Ginzburg-Landau equation), which is derived directly from the underlying equations of motion of the coupled resonators, using the method of multiple scales. We investigate the creation, stability, and interaction of ILMs, show that they can form bound states, and that under certain conditions one ILM can split into two. Our findings are confirmed by simulations of the underlying equations of motion of the resonators, suggesting possible experimental tests of the theory.