In vivo facilitated diffusion model

Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.Comment: 19 pages, 9 figures, Supplementary Information directly include

Diffusion of finite-size particles in channels with random walls

Diffusion of chemicals or tracer molecules through complex systems containing irregularly shaped channels is important in many applications. Most theoretical studies based on the famed Fick-Jacobs equation focus on the idealised case of infinitely small particles and reflecting boundaries. In this study we use numerical simulations to consider the transport of finite-sized particles through asymmetrical two-dimensional channels. Additionally, we examine transient binding of the molecules to the channel walls by applying sticky boundary conditions. With the application of diffusing pathogens in hydrogels in mind, we consider an ensemble of particles diffusing in independent channels, which are characterised by common structural parameters. We compare our results for the long-time effective diffusion coefficient with a recent theoretical formula obtained by Dagdug and Pineda [J. Chem. Phys., 2012, 137, 024107].Comment: 10 pages, 12 figures, RevTe

Collective dynamics effect transient subdiffusion of inert tracers in gel networks

Based on extensive Brownian dynamics simulations we study the thermally driven motion of a tracer bead in a cross-linked, dynamic gel network in the limit when the tracer bead's size is of the same size or even larger than the equilibrium mesh size of the gel. The analysis of long individual trajectories of the tracer bead demonstrates the existence of pronounced transient anomalous diffusion, accompanied by a drastic slow-down of the gel-bead relaxation dynamics. From the time averaged mean squared displacement and the van Hove cross-correlation function we elucidate the many-body origin of the non-Brownian tracer bead dynamics. Our results shed new light on the ongoing debate over the physical origin of sterical tracer interactions with structured environments.Comment: 5 pages, 4 figures, RevTe

Continuous-Wave Nd:YVO4 self-Raman lasers operating at 1109nm, 1158nm and 1231nm

Several continuous-wave Nd:YVO4 self-Raman lasers based on the primary and secondary Raman transitions of YVO4 (893cm−1 and 379cm−1 respectively) are reported in this paper. Laser outputs were obtained at a wavelength of 1109nm, 1158nm and 1231nm with maximum output powers of 1.0W, 700mW and 540mW respectively. The respective absorbed pump power to Raman output power conversion efficiencies were measured at 8.4%, 5.4%, and 5.4%

Applications of programmable MEMS micromirrors in laser systems

The use of optical microelectromechanical systems (MEMS) as enabling devices has been shown widely over the last decades, creating miniaturisation possibilities and added functionality for photonic systems. In the work presented in this thesis angular vertical offset comb-drive (AVC) actuated scanning micromirrors, and their use as intracavity active Q-switch elements in solid-state laser systems, are investigated. The AVC scanning micromirrors are created through a multi-user fabrication process, with theoretical and experimental investigations undertaken on the influence of the AVC initial conditions on the scanning micromirror dynamic resonant tilt movement behaviour. A novel actuator geometry is presented to experimentally investigate this influence, allowing a continuous variation of the initial AVC comb-offset angle through an integrated electrothermal actuator. The experimentally observed changes of the resonant movement with varying initial AVC offset are compared with an analytical model, simulating this varying resonant movement behaviour. In the second part of this work AVC scanning micromirrors are implemented as active intra-cavity Q-switch elements of a Nd:YAG solid-state laser system. The feasibility of achieving pulsed laser outputs with pulse durations limited by the laser cavity and not the MEMS Q-switch is shown, combined with a novel theoretical model for the Q-switch behaviour of the laser when using a bi-directional intra-cavity scanning micromirror. A detailed experimental investigation of the pulsed laser output behaviour for varying laser cavity geometries is presented, also discussing the influence of thin film coatings deposited on the mirror surfaces for further laser output power scaling. The MEMS Q-switch system is furthermore expanded using a micromirror array to create a novel Q-switched laser system with multiple individual controllable output beams using a common solid-state gain medium. Experimental results showing the simultaneous generation of two laser outputs are presented, with cavity limited pulse durations and excellent laser beam quality.The use of optical microelectromechanical systems (MEMS) as enabling devices has been shown widely over the last decades, creating miniaturisation possibilities and added functionality for photonic systems. In the work presented in this thesis angular vertical offset comb-drive (AVC) actuated scanning micromirrors, and their use as intracavity active Q-switch elements in solid-state laser systems, are investigated. The AVC scanning micromirrors are created through a multi-user fabrication process, with theoretical and experimental investigations undertaken on the influence of the AVC initial conditions on the scanning micromirror dynamic resonant tilt movement behaviour. A novel actuator geometry is presented to experimentally investigate this influence, allowing a continuous variation of the initial AVC comb-offset angle through an integrated electrothermal actuator. The experimentally observed changes of the resonant movement with varying initial AVC offset are compared with an analytical model, simulating this varying resonant movement behaviour. In the second part of this work AVC scanning micromirrors are implemented as active intra-cavity Q-switch elements of a Nd:YAG solid-state laser system. The feasibility of achieving pulsed laser outputs with pulse durations limited by the laser cavity and not the MEMS Q-switch is shown, combined with a novel theoretical model for the Q-switch behaviour of the laser when using a bi-directional intra-cavity scanning micromirror. A detailed experimental investigation of the pulsed laser output behaviour for varying laser cavity geometries is presented, also discussing the influence of thin film coatings deposited on the mirror surfaces for further laser output power scaling. The MEMS Q-switch system is furthermore expanded using a micromirror array to create a novel Q-switched laser system with multiple individual controllable output beams using a common solid-state gain medium. Experimental results showing the simultaneous generation of two laser outputs are presented, with cavity limited pulse durations and excellent laser beam quality

NO2 Limb Retrieval in the Upper Troposphere/ Lower Stratosphere Region

As reactive nitrogen amounts in the stratosphere increase, accurate measurements of these trace gases is of high importance. The SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric CHartog raphY) instrument on ENVISAT (European Environmental Satellite) performs measurements in limb geometry since 2002, providing global coverage of NO2 retrieval results every six days. In this study, a novel approach to improve the sensitivity of SCIAMACHY NO2 limb retrieval results at the UTLS (Upper Troposphere/ Lower Stratosphere) altitude layer is described. Additionally, the current NO2 limb retrieval product is validated in detail and both methods are used for case studies at the North Atlantic region

Real sequence effects on the search dynamics of transcription factors on DNA

Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.Comment: 26 pages, 7 figure

MEMS micromirror based light sheet generator for biomedical imaging

Two MEMS micromirrors with resonant or static actuation are used as a MEMS enabled light sheet generator, with light sheet dimensions of 3.5μm by 550μm and offset positioning of 150μm in the focal plane

Dual Q-switched laser outputs from a single lasing medium using an intracavity MEMS micromirror array

An intracavity array of individually controlled microelectromechanical system scanning micromirrors was used to actively Q-switch a single side-pumped Nd:YAG gain medium. Two equal power independent laser outputs were simultaneously obtained by separate actuation of two adjacent micromirrors with a combined average output power of 125 mW. Pulse durations of 28 ns FWHM at 8.7 kHz repetition frequency and 34 ns FWHM at 7.9 kHz repetition frequency were observed for the two output beams with beam quality factors M2 of 1.2 and 1.1 and peak powers of 253 W and 232 W, respectively

Light-sheet microscopy using MEMS and active optics for 3D image acquisition control

A miniaturized version of a light-sheet microscopy (LSM) system, with 3D imaging enabled through active optical control, is presented. Even though the field of LSM technology has advanced significantly in recent years, it is still not considered an easily available technique. This is mainly due to its cost compared to epifluorescence setups and the requirement for specific sample mounting techniques in most cases, as well as stringent optical alignment and difficulty to reduce motion artifacts when the sample is moved through the light path to create the imaging slices. In our research, we demonstrate a miniaturized version of an LSM that can reduce size and cost, and is able to achieve 3D imaging through control of multiple active optical elements and MEMS micromirrors used in both the illumination and imaging path instead of moving the sample. The laser excitation is controlled and shaped via multiple MEMS elements for 3D beam position control and multilens beam shaping to generate a 2.85 μm wide light-sheet with controllable height of up to 550 μm, and orthogonal positioning over a 200 μm range. Additionally, the focal point of the excitation can be shifted along the laser propagation direction by 200 μm. The orthogonally positioned imaging path incorporates a x20, NA = 0.4 objective and a tunable lens for imaging selected focal planes synchronized with the excitation positioning. The imaging results show sub-micron resolution with a field-of-view of 400 μm x 300 μm. The synchronization of the two active elements allows for fast imaging of different slices of a sample and promises convenient 3D reconstruction and representation of cell tissue