Electric Pulses to Prepare Feeder Cells for Sustaining and Culturing of Undifferentiated Embryonic Stem Cells

Current challenges in embryonic-stem-cell (ESC) research include inability of sustaining and culturing of undifferentiated ESCs over time. Growth-arrested feeder cells are essential to the culture and sustaining of undifferentiated ESCs, and they are currently prepared using gammaradiation and chemical inactivation. Both techniques have severe limitations. In this study, we developed a new, simple and effective technique (pulsed-electric-fields, PEFs) to produce viable growth-arrested cells (RTS34st) and used them as high-quality feeder cells to culture and sustain undifferentiated zebrafish ESCs over time. The cells were exposed to 25 sequential 10- nanosecond-electric-pulses (10nsEPs) of 25, 40 and 150 kV/cm with 1s pulse interval, or 2 sequential 50-microsecond-electric-pulses (50μsEPs) of 2.83, 1.78 and 0.7 kV/cm with 5s pulse interval, respectively. We found that cellular effects of PEFs depended directly upon the duration, number and electric-field-strength (E) of the pulses, showing the feasibility of tuning them to produce various types of growth-arrested cells for culturing undifferentiated ESCs. Either 10nsEPs of 40 kV/cm or 50μsEPs of 1.78 kV/cm provided by inexpensive and widely available conventional electroporators, generated high-quality growth-arrested feeder cells for proliferation of undifferentiated ESCs over time. One can now use PEFs to replace radiation methods for preparation of growth-arrested feeder cells for advancing ESC research

Real-Time in vivo Imaging of Size-Dependent Transport and Toxicity of Gold Nanoparticles in Zebrafish Embryos Using Single Nanoparticle Plasmonic Spectroscopy

Noble metal nanoparticles (NPs) show distinctive plasmonic optical properties and superior photostability, enabling them to serve as photostable multicoloured optical molecular probes and sensors for real-time in vivo imaging. To effectively study biological functions in vivo, it is essential that the NP probes are biocompatible and can be delivered into living organisms non-invasively. In this study, we have synthesized, purified and characterized stable (non-aggregated) gold (Au) NPs (86.2 +/- 10.8 nm). We have developed dark-field single NP plasmonic microscopy and spectroscopy to study their transport into early developing zebrafish embryos (cleavage stage) and their effects on embryonic development in real-time at single NP resolution. We found that single Au NPs (75-97 nm) passively diffused into the embryos via their chorionic pore canals, and stayed inside the embryos throughout their entire development (120 h). The majority of embryos (96 +/- 3%) that were chronically incubated with the Au NPs (0-20 pM) for 120 h developed to normal zebrafish, while an insignificant percentage of embryos developed to deformed zebrafish (1 +/- 1)% or dead (3 +/- 3)%. Interestingly, we did not observe dose-dependent effects of the Au NPs (0-20 pM) on embryonic development. By comparing with our previous studies of smaller Au NPs (11.6 +/- 0.9 nm) and similar-sized Ag NPs (95.4 +/- 16.0 nm), we found that the larger Au NPs are more biocompatible than the smaller Au NPs, while the similar-sized Ag NPs are much more toxic than Au NPs. This study offers in vivo assays and single NP microscopy and spectroscopy to characterize the biocompatibility and toxicity of single NPs, and new insights into the rational design of more biocompatible plasmonic NP imaging probes

Model reconstruction from temporal data for coupled oscillator networks

In a complex system, the interactions between individual agents often lead to emergent collective behavior like spontaneous synchronization, swarming, and pattern formation. The topology of the network of interactions can have a dramatic influence over those dynamics. In many studies, researchers start with a specific model for both the intrinsic dynamics of each agent and the interaction network, and attempt to learn about the dynamics that can be observed in the model. Here we consider the inverse problem: given the dynamics of a system, can one learn about the underlying network? We investigate arbitrary networks of coupled phase-oscillators whose dynamics are characterized by synchronization. We demonstrate that, given sufficient observational data on the transient evolution of each oscillator, one can use machine learning methods to reconstruct the interaction network and simultaneously identify the parameters of a model for the intrinsic dynamics of the oscillators and their coupling.Comment: 27 pages, 7 figures, 16 table

Single-bubble dynamics in histotripsy and high-amplitude ultrasound: Modeling and validation

A variety of approaches have been used to model the dynamics of a single, isolated bubble nucleated by a microsecond length high-amplitude ultrasound pulse (e.g., a histotripsy pulse). Until recently, the lack of single--bubble experimental radius vs. time data for bubble dynamics under a well-characterized driving pressure has limited model validation efforts. This study uses radius vs. time measurements of single, spherical histotripsy-nucleated bubbles in water [Wilson et al., Phys. Rev. E, 2019, 99, 043103] to quantitatively compare and validate a variety of bubble dynamics modeling approaches, including compressible and incompressible models as well as different thermal models. A strategy for inferring an analytic representation of histotripsy waveforms directly from experimental radius vs. time and cavitation threshold data is presented. We compare distributions of a calculated validation metric obtained for each model applied to $88$ experimental data sets. There is minimal distinction ($< 1\%$) among the modeling approaches for compressibility and thermal effects considered in this study. These results suggest that our proposed strategy to infer the waveform, combined with simple models minimizing parametric uncertainty and computational resource demands accurately represent single-bubble dynamics in histotripsy, including at and near the maximum bubble radius. Remaining sources of parametric and model-based uncertainty are discussed

Synthesizing Quantum-Circuit Optimizers

Near-term quantum computers are expected to work in an environment where each operation is noisy, with no error correction. Therefore, quantum-circuit optimizers are applied to minimize the number of noisy operations. Today, physicists are constantly experimenting with novel devices and architectures. For every new physical substrate and for every modification of a quantum computer, we need to modify or rewrite major pieces of the optimizer to run successful experiments. In this paper, we present QUESO, an efficient approach for automatically synthesizing a quantum-circuit optimizer for a given quantum device. For instance, in 1.2 minutes, QUESO can synthesize an optimizer with high-probability correctness guarantees for IBM computers that significantly outperforms leading compilers, such as IBM's Qiskit and TKET, on the majority (85%) of the circuits in a diverse benchmark suite. A number of theoretical and algorithmic insights underlie QUESO: (1) An algebraic approach for representing rewrite rules and their semantics. This facilitates reasoning about complex symbolic rewrite rules that are beyond the scope of existing techniques. (2) A fast approach for probabilistically verifying equivalence of quantum circuits by reducing the problem to a special form of polynomial identity testing. (3) A novel probabilistic data structure, called a polynomial identity filter (PIF), for efficiently synthesizing rewrite rules. (4) A beam-search-based algorithm that efficiently applies the synthesized symbolic rewrite rules to optimize quantum circuits.Comment: Full version of PLDI 2023 pape

Voltage gated inter-cation selective ion channels from graphene nanopores

With the ability to selectively control ionic flux, biological protein ion channels perform a fundamental role in many physiological processes. For practical applications that require the functionality of a biological ion channel, graphene provides a promising solid-state alternative, due to its atomic thinness and mechanical strength. Here, we demonstrate that nanopores introduced into graphene membranes, as large as 50 nm in diameter, exhibit inter-cation selectivity with a ~20x preference for K+ over divalent cations and can be modulated by an applied gate voltage. Liquid atomic force microscopy of the graphene devices reveals surface nanobubbles near the pore to be responsible for the observed selective behavior. Molecular dynamics simulations indicate that translocation of ions across the pore likely occurs via a thin water layer at the edge of the pore and the nanobubble. Our results demonstrate a significant improvement in the inter-cation selectivity displayed by a solid-state nanopore device and by utilizing the pores in a de-wetted state, offers an approach to fabricating selective graphene membranes that does not rely on the fabrication of sub-nm pores

Kirigami-inspired, highly stretchable micro-supercapacitor patches fabricated by laser conversion and cutting.

The recent developments in material sciences and rational structural designs have advanced the field of compliant and deformable electronics systems. However, many of these systems are limited in either overall stretchability or areal coverage of functional components. Here, we design a construct inspired by Kirigami for highly deformable micro-supercapacitor patches with high areal coverages of electrode and electrolyte materials. These patches can be fabricated in simple and efficient steps by laser-assisted graphitic conversion and cutting. Because the Kirigami cuts significantly increase structural compliance, segments in the patches can buckle, rotate, bend and twist to accommodate large overall deformations with only a small strain (&lt;3%) in active electrode areas. Electrochemical testing results have proved that electrical and electrochemical performances are preserved under large deformation, with less than 2% change in capacitance when the patch is elongated to 382.5% of its initial length. The high design flexibility can enable various types of electrical connections among an array of supercapacitors residing in one patch, by using different Kirigami designs

Regularly log-periodic functions and some applications

We prove a Tauberian theorem for the Laplace--Stieltjes transform and Karamata-type theorems in the framework of regularly log-periodic functions. As an application we determine the exact tail behavior of fixed points of certain type smoothing transforms