Excitation energy transfer: Study with non-Markovian dynamics

In this paper, we investigate the non-Markovian dynamics of a model to mimic the excitation energy transfer (EET) between chromophores in photosynthesis systems. The numerical path integral method is used. This method includes the non-Markovian effects of the environmental affects and it does not need the perturbation approximation in solving the dynamics of systems of interest. It implies that the coherence helps the EET between chromophores through lasting the transfer time rather than enhances the transfer rate of the EET. In particular, the non-Markovian environment greatly increase the efficiency of the EET in the photosynthesis systems.Comment: 5 pages, 5 figure

Integrated assessment of neurocognitive, neurophysiological and pain processing in early clinical drug development

The thesis describes the use of extensive pharmacodynamic effect profiling to characterise the clinical pharmacology of classic and non-classical analgesia. Analgesic drugs that modulate widespread targets in the nervous system can be expected to affect numerous CNS functions, which requires multimodal characterisation of pain processing and neurocognition. This is illustrated on the basis of two case studies of pharmacological agents that target cannabinoid CB1 and GABA-ergic GABAA receptors: two of the most widely distributed systems of receptors and neurotransmitters that are involved in a myriad of physiological functions. The distribution of receptors throughout the central nervous system render an oral formulation of ∆9-THC and a positive allosteric modulator of α2/3/5 subunit-containing GABAA receptors, ideal candidates for extensive neurophysiological and analgesic effect profiling in early phase clinical research. Profiling human pharmacology with a strong focus on pharmacodynamics may help to better understand the therapeutic potential and safety limitations of a compound before selection of doses and patient populations for phase II proof-of-concept studies.LUMC / Geneeskund

Linear motor motion control using a learning feedforward controller

The design and realization of an online learning motion controller for a linear motor is presented, and its usefulness is evaluated. The controller consists of two components: (1) a model-based feedback component, and (2) a learning feedforward component. The feedback component is designed on the basis of a simple second-order linear model, which is known to have structural errors. In the design, an emphasis is placed on robustness. The learning feedforward component is a neural-network-based controller, comprised of a one-hidden-layer structure with second-order B-spline basis functions. Simulations and experimental evaluations show that, with little effort, a high-performance motion system can be obtained with this approach

Quantitative live-cell imaging and computational modelling shed new light on endogenous WNT/CTNNB1 signaling dynamics

WNT/CTNNB1 signaling regulates tissue development and homeostasis in all multicellular animals, but the underlying molecular mechanism remains incompletely understood. Specifically, quantitative insight into endogenous protein behavior is missing. Here, we combine CRISPR/Cas9-mediated genome editing and quantitative live-cell microscopy to measure the dynamics, diffusion characteristics and absolute concentrations of fluorescently tagged, endogenous CTNNB1 in human cells under both physiological and oncogenic conditions. State-of-the-art imaging reveals that a substantial fraction of CTNNB1 resides in slow-diffusing cytoplasmic complexes, irrespective of the activation status of the pathway. This cytoplasmic CTNNB1 complex undergoes a major reduction in size when WNT/CTNNB1 is (hyper)activated. Based on our biophysical measurements, we build a computational model of WNT/CTNNB1 signaling. Our integrated experimental and computational approach reveals that WNT pathway activation regulates the dynamic distribution of free and complexed CTNNB1 across different subcellular compartments through three regulatory nodes: the destruction complex, nucleocytoplasmic shuttling, and nuclear retention

Efficiency of energy transfer in a light-harvesting system under quantum coherence

We investigate the role of quantum coherence in the efficiency of excitation transfer in a ring-hub arrangement of interacting two-level systems, mimicking a light-harvesting antenna connected to a reaction center as it is found in natural photosynthetic systems. By using a quantum jump approach, we demonstrate that in the presence of quantum coherent energy transfer and energetic disorder, the efficiency of excitation transfer from the antenna to the reaction center depends intimately on the quantum superposition properties of the initial state. In particular, we find that efficiency is sensitive to symmetric and asymmetric superposition of states in the basis of localized excitations, indicating that initial state properties can be used as a efficiency control parameter at low temperatures.Comment: Extended version of original paper. 7 pages, 2 figure

Influence of the relative humidity on the morphology of inkjet printed spots of IgG on a non-porous substrate

During the drying of inkjet printed droplets, the solute particles (IgG-Alexa-635 molecules) in the drop may distribute unevenly on the substrate, resulting in a coffee-stain spot morphology. In our study, we investigated the influence of the relative humidity on the distribution of inkjet printed fluorophore labeled IgG molecules on a polystyrene substrate. A theoretical model for an evaporating droplet was developed in order to predict the changes in the spot diameter, height and volume of a drying droplet. An experiment was performed where a sessile droplet was monitored using a CCD camera installed on a goniometer and good agreement was found between the experimental results and simulation data. We also compared the predicted morphology for an inkjet-printed microarray spot with the experimental results where IgG molecules were printed for various relative humidities. The spot morphology of the dried spots was analyzed by a confocal laser microscopy. At a lower relative humidity (i.e.

Efficient estimation of energy transfer efficiency in light-harvesting complexes

The fundamental physical mechanisms of energy transfer in photosynthetic complexes is not yet fully understood. In particular, the degree of efficiency or sensitivity of these systems for energy transfer is not known given their non-perturbative and non-Markovian interactions with proteins backbone and surrounding photonic and phononic environments. One major problem in studying light-harvesting complexes has been the lack of an efficient method for simulation of their dynamics in biological environments. To this end, here we revisit the second-order time-convolution (TC2) master equation and examine its reliability beyond extreme Markovian and perturbative limits. In particular, we present a derivation of TC2 without making the usual weak system-bath coupling assumption. Using this equation, we explore the long time behaviour of exciton dynamics of Fenna-Matthews-Olson (FMO) protein complex. Moreover, we introduce a constructive error analysis to estimate the accuracy of TC2 equation in calculating energy transfer efficiency, exhibiting reliable performance for environments with weak and intermediate memory and strength. Furthermore, we numerically show that energy transfer efficiency is optimal and robust for the FMO protein complex of green sulphur bacteria with respect to variations in reorganization energy and bath correlation time-scales.Comment: 16 pages, 9 figures, modified version, updated appendices and reference lis

Simian immunodeficiency virus (SIV)-specific CD8+ cytotoxic T lymphocyte responses of naive and vaccinated cynomolgus macaques infected with (SIV)mac32H(J5): quantitative analysis by in vitro antigenic stimulation.

Detailed analyses of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocyte (CTL) responses in vaccinated and infected macaques may help to clarify the role of CTL immunity in protection against lentiviruses. Here, the optimal conditions for the measurement of SIV Gag-specific CTL were investigated by bulk and limiting dilution assays of peripheral blood mononuclear cells (PBMC) from naive and vaccinated cynomolgus macaques (Macaca fascicularis) infected with SIVmac32H(J5). In vitro restimulation was generally required for CTL detection. Selective activation of CD8+ and MHC-restricted SIV Gag-specific CTL was induced by stimulation with autologous para-formaldehyde-fixed B-lymphoblastoid cell lines infected with a recombinant vaccinia virus expressing SIV Gag. Applied to limiting dilution assays, antigenic stimulation reproducibly demonstrated SIV Gag-specific CTL precursors (CTLp) in PBMC of all animals studied, including those lacking significant responses in standard bulk CTL assays

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug's pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action. Perioperative Medicine: Efficacy, Safety and Outcom