Temperature Modulation of Electric Fields in Biological Matter

Pulsed electric fields (PEF) have become an important minimally invasive surgical technology for various applications including genetic engineering, electrochemotherapy and tissue ablation. This study explores the hypothesis that temperature dependent electrical parameters of tissue can be used to modulate the outcome of PEF protocols, providing a new means for controlling and optimizing this minimally invasive surgical procedure. This study investigates two different applications of cooling temperatures applied during PEF. The first case utilizes an electrode which simultaneously delivers pulsed electric fields and cooling temperatures. The subsequent results demonstrate that changes in electrical properties due to temperature produced by this configuration can substantially magnify and confine the electric fields in the cooled regions while almost eliminating electric fields in surrounding regions. This method can be used to increase precision in the PEF procedure, and eliminate muscle contractions and damage to adjacent tissues. The second configuration considered introduces a third probe that is not electrically active and only applies cooling boundary conditions. This second study demonstrates that in this probe configuration the temperature induced changes in electrical properties of tissue substantially reduce the electric fields in the cooled regions. This novel treatment can potentially be used to protect sensitive tissues from the effect of the PEF. Perhaps the most important conclusion of this investigation is that temperature is a powerful and accessible mechanism to modulate and control electric fields in biological tissues and can therefore be used to optimize and control PEF treatments

A combined model reduction algorithm for controlled biochemical systems

Background: Systems Biology continues to produce increasingly large models of complex biochemical reaction networks. In applications requiring, for example, parameter estimation, the use of agent-based modelling approaches, or real-time simulation, this growing model complexity can present a significant hurdle. Often, however, not all portions of a model are of equal interest in a given setting. In such situations methods of model reduction offer one possible approach for addressing the issue of complexity by seeking to eliminate those portions of a pathway that can be shown to have the least effect upon the properties of interest. Methods: In this paper a model reduction algorithm bringing together the complementary aspects of proper lumping and empirical balanced truncation is presented. Additional contributions include the development of a criterion for the selection of state-variable elimination via conservation analysis and use of an ‘averaged’ lumping inverse. This combined algorithm is highly automatable and of particular applicability in the context of ‘controlled’ biochemical networks. Results: The algorithm is demonstrated here via application to two examples; an 11 dimensional model of bacterial chemotaxis in Escherichia coli and a 99 dimensional model of extracellular regulatory kinase activation (ERK) mediated via the epidermal growth factor (EGF) and nerve growth factor (NGF) receptor pathways. In the case of the chemotaxis model the algorithm was able to reduce the model to 2 state-variables producing a maximal relative error between the dynamics of the original and reduced models of only 2.8% whilst yielding a 26 fold speed up in simulation time. For the ERK activation model the algorithm was able to reduce the system to 7 state-variables, incurring a maximal relative error of 4.8%, and producing an approximately 10 fold speed up in the rate of simulation. Indices of controllability and observability are additionally developed and demonstrated throughout the paper. These provide insight into the relative importance of individual reactants in mediating a biochemical system’s input-output response even for highly complex networks. Conclusions: Through application, this paper demonstrates that combined model reduction methods can produce a significant simplification of complex Systems Biology models whilst retaining a high degree of predictive accuracy. In particular, it is shown that by combining the methods of proper lumping and empirical balanced truncation it is often possible to produce more accurate reductions than can be obtained by the use of either method in isolation

Methods of model reduction for large-scale biological systems: a survey of current methods and trends

Complex models of biochemical reaction systems have become increasingly common in the systems biology literature. The complexity of such models can present a number of obstacles for their practical use, often making problems difficult to intuit or computationally intractable. Methods of model reduction can be employed to alleviate the issue of complexity by seeking to eliminate those portions of a reaction network that have little or no effect upon the outcomes of interest, hence yielding simplified systems that retain an accurate predictive capacity. This review paper seeks to provide a brief overview of a range of such methods and their application in the context of biochemical reaction network models. To achieve this, we provide a brief mathematical account of the main methods including timescale exploitation approaches, reduction via sensitivity analysis, optimisation methods, lumping, and singular value decomposition-based approaches. Methods are reviewed in the context of large-scale systems biology type models, and future areas of research are briefly discussed

First M87 Event Horizon Telescope Results. VII. Polarization of the Ring

In 2017 April, the Event Horizon Telescope (EHT) observed the near-horizon region around the supermassive black hole at the core of the M87 galaxy. These 1.3 mm wavelength observations revealed a compact asymmetric ring-like source morphology. This structure originates from synchrotron emission produced by relativistic plasma located in the immediate vicinity of the black hole. Here we present the corresponding linear-polarimetric EHT images of the center of M87. We find that only a part of the ring is significantly polarized. The resolved fractional linear polarization has a maximum located in the southwest part of the ring, where it rises to the level of similar to 15%. The polarization position angles are arranged in a nearly azimuthal pattern. We perform quantitative measurements of relevant polarimetric properties of the compact emission and find evidence for the temporal evolution of the polarized source structure over one week of EHT observations. The details of the polarimetric data reduction and calibration methodology are provided. We carry out the data analysis using multiple independent imaging and modeling techniques, each of which is validated against a suite of synthetic data sets. The gross polarimetric structure and its apparent evolution with time are insensitive to the method used to reconstruct the image. These polarimetric images carry information about the structure of the magnetic fields responsible for the synchrotron emission. Their physical interpretation is discussed in an accompanying publication

The Event Horizon Telescope Image of the Quasar NRAO 530

We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5−7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of ∼20 μas, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of ∼5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 μas along a position angle ∼ −28°. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin

Ordered magnetic fields around the 3C 84 central black hole

Context. 3C 84 is a nearby radio source with a complex total intensity structure, showing linear polarisation and spectral patterns. A detailed investigation of the central engine region necessitates the use of very-long-baseline interferometry (VLBI) above the hitherto available maximum frequency of 86 GHz.Aims. Using ultrahigh resolution VLBI observations at the currently highest available frequency of 228 GHz, we aim to perform a direct detection of compact structures and understand the physical conditions in the compact region of 3C 84.Methods. We used Event Horizon Telescope (EHT) 228 GHz observations and, given the limited (u; v)-coverage, applied geometric model fitting to the data. Furthermore, we employed quasi-simultaneously observed, ancillary multi-frequency VLBI data for the source in order to carry out a comprehensive analysis of the core structure.Results. We report the detection of a highly ordered, strong magnetic field around the central, supermassive black hole of 3C 84. The brightness temperature analysis suggests that the system is in equipartition. We also determined a turnover frequency of gamma(m) = (113 +/- 4) GHz, a corresponding synchrotron self-absorbed magnetic field of B-SSA = (2.9 +/- 1.6) G, and an equipartition magnetic field of B-eq = (5.2 +/- 0.6) G. Three components are resolved with the highest fractional polarisation detected for this object (m(net) = (17.0 +/- 3.9)%). The positions of the components are compatible with those seen in low-frequency VLBI observations since 2017-2018. We report a steeply negative slope of the spectrum at 228 GHz. We used these findings to test existing models of jet formation, propagation, and Faraday rotation in 3C 84.Conclusions. The findings of our investigation into di fferent flow geometries and black hole spins support an advection-dominated accretion flow in a magnetically arrested state around a rapidly rotating supermassive black hole as a model of the jet-launching system in the core of 3C 84. However, systematic uncertainties due to the limited (u, v)-coverage, however, cannot be ignored. Our upcoming work using new EHT data, which offer full imaging capabilities, will shed more light on the compact region of 3C 84