Lifetime of actin-dependent protein nanoclusters

Protein nanoclusters (PNCs) are dynamic collections of a few proteins that spatially organize in nanometer length clusters. PNCs are one of the principal forms of spatial organization of membrane proteins and they have been shown or hypothesized to be important in various cellular processes, including cell signaling. PNCs show remarkable diversity in size, shape, and lifetime. In particular, the lifetime of PNCs can vary over a wide range of timescales. The diversity in size and shape can be explained by the interaction of the clustering proteins with the actin cytoskeleton or the lipid membrane, but very little is known about the processes that determine the lifetime of the nanoclusters. In this paper, using mathematical modelling of the cluster dynamics, we model the biophysical processes that determine the lifetime of actin-dependent PNCs. In particular, we investigated the role of actin aster fragmentation, which had been suggested to be a key determinant of the PNC lifetime, and found that it is important only for a small class of PNCs. A simple extension of our model allowed us to investigate the kinetics of protein-ligand interaction near PNCs. We found an anomalous increase in the lifetime of ligands near PNCs, which agrees remarkably well with experimental data on RAS-RAF kinetics. In particular, analysis of the RAS-RAF data through our model provides falsifiable predictions and novel hypotheses that will not only shed light on the role of RAS-RAF kinetics in various cancers, but also will be useful in studying membrane protein clustering in general.

An Efficient Δ-Circuit approach for Online Short-Circuit Calculation in Large Islanded AC Microgrids

In this manuscript, a novel Δ-circuit approach is proposed, which enables the fast calculation of fault currents in large islanded AC microgrids (MGs), supplied by inverter-based distributed generators (IBDGs) with virtual impedance current limiters (VICLs). The concept of virtual impedance for limiting the fault current of IBDGs has gained the interest of research community in the recent years, due to the strong advantages it offers. Moreover, Δ-circuit is an efficient approach, which has been widely applied in the past, for the calculation of short?circuit currents of transmission and distribution networks. However, the traditional Δ-circuit, in its current form, is not applicable in islanded MGs, due to the particular characteristics of such networks, e.g., the absence of a slack bus. To overcome this issue, a novel Δ-circuit approach is proposed in this paper, with the following distinct features: a) precise simulation of islanded MGs, b) fast computational performance, c) generic applicability in all types of faults e.g., single-line, 2-line or 3-line faults, d) simple extension to other DG current limiting modes, e.g., latched limit strategy etc. The proposed approach is validated through the time-domain software of Matlab Simulink, in a 9-bus and 13-bus islanded MG. The computational performance of the proposed fault analysis method is further tested in a modified islanded version of the IEEE 8500-node network.

An Efficient Δ-Circuit approach for Online Short-Circuit Calculation in Large Islanded AC Microgrids

In this manuscript, a novel Δ-circuit approach is proposed, which enables the fast calculation of fault currents in large islanded AC microgrids (MGs), supplied by inverter-based distributed generators (IBDGs) with virtual impedance current limiters (VICLs). The concept of virtual impedance for limiting the fault current of IBDGs has gained the interest of research community in the recent years, due to the strong advantages it offers. Moreover, Δ-circuit is an efficient approach, which has been widely applied in the past, for the calculation of short?circuit currents of transmission and distribution networks. However, the traditional Δ-circuit, in its current form, is not applicable in islanded MGs, due to the particular characteristics of such networks, e.g., the absence of a slack bus. To overcome this issue, a novel Δ-circuit approach is proposed in this paper, with the following distinct features: a) precise simulation of islanded MGs, b) fast computational performance, c) generic applicability in all types of faults e.g., single-line, 2-line or 3-line faults, d) simple extension to other DG current limiting modes, e.g., latched limit strategy etc. The proposed approach is validated through the time-domain software of Matlab Simulink, in a 9-bus and 13-bus islanded MG. The computational performance of the proposed fault analysis method is further tested in a modified islanded version of the IEEE 8500-node network.

IL-3 Changing Cancer Genomics and Cancer Genomic Medicine by Artificial Intelligence and Large-Scale Data Analysis

In MEXT Program for Scientific Research on Innovative Areas “Systems Cancer” and “Systems Cancer in Neo-Dimension” (2010-2019), we developed a large-scale genome data analysis pipeline called Genomon in collaboration with Professor Seiji Ogawa (Kyoto University). Our efforts successfully produced innovative results on cancer genomics. This system is implemented on the supercomputers SHIROKANE and FUGAKU. One of the contributions unraveled the overall picture of genetic abnormalities in malignant brain tumors (Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 2015) that exploited Genomon on SHIROKANE. However, with the spread of new measurement technology and new computing environments, no one thinks that the future can be figured on this simple extension. On the other hand, for cancer genomic medicine, Institute of Medical Science University of Tokyo made a research team analyzing whole genome sequences. The challenge we faced was to transform thousands to millions of genomic aberrations per case into precision medicine. It is what we now call “digital transformation.” IBM’s Watson for Genomics was introduced for our research purpose. In the process, we identified the effectiveness of AI, the indispensability of specialist intervention, and bottlenecks. We recognized that natural language processing technology such as BERT and Google Knowledge Graph AI technology will open up the future. Automatic document creation is also a realistic issue. Cancer research is getting more difficult and larger in scale. For example, analysis of genomic data from 60, 954 cases revealed a new underlying mechanism in which multiple mutations within the same oncogene synergistically work (Nature 2021). AI with an accuracy of X% does not seem to be the goal. What is needed is not a black box, but explainable AI that explains “why” in a human-understandable way. We are currently conducting research with Fujitsu Laboratories for this direction.

Spherical Scanning 3-D Microwave Imaging of Near-field Scatterers Mutually Coupled With an Antenna Array

<div>*This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible.<br></div><div><br></div>In this article, we propose a 3-D synthetic aperture imaging method with spherical antenna scanning to identify scatterers located close to an antenna array, such as fixtures or support of the antenna. Previous studies have shown that 2-D and 3-D synthetic aperture imaging techniques with planar, circular, and cylindrical scanning can successfully reconstruct spatial images of near-field scatterers. The spherical scanning approach considered in this article is expected to improve the 3-D image resolution because more angular diversity can be achieved in the elevation direction. However, as we show in this study, simple extension of the previous techniques to the spherical case results in undesired blur artifacts in the reconstructed image. To overcome this problem, we introduce a correction factor in the image reconstruction. The proposed imaging algorithm is validated by numerical electromagnetic simulation based on the method of moments.

Spherical Scanning 3-D Microwave Imaging of Near-field Scatterers Mutually Coupled With an Antenna Array

<div>*This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible.<br></div><div><br></div>In this article, we propose a 3-D synthetic aperture imaging method with spherical antenna scanning to identify scatterers located close to an antenna array, such as fixtures or support of the antenna. Previous studies have shown that 2-D and 3-D synthetic aperture imaging techniques with planar, circular, and cylindrical scanning can successfully reconstruct spatial images of near-field scatterers. The spherical scanning approach considered in this article is expected to improve the 3-D image resolution because more angular diversity can be achieved in the elevation direction. However, as we show in this study, simple extension of the previous techniques to the spherical case results in undesired blur artifacts in the reconstructed image. To overcome this problem, we introduce a correction factor in the image reconstruction. The proposed imaging algorithm is validated by numerical electromagnetic simulation based on the method of moments.

Fermion singlet dark matter in a pseudoscalar dark matter portal

We explore a simple extension to the Standard Model containing two gauge singlets: a Dirac fermion and a real pseudoscalar. In some regions of the parameter space both singlets are stable without the necessity of additional symmetries, then becoming a possible two-component dark matter model. We study the relic abundance production via freeze-out, with the latter determined by annihilations, conversions and semi-annihilations. Experimental constraints from invisible Higgs decay, dark matter relic abundance and direct/indirect detection are studied. We found three viable regions of the parameter space, and the model is sensitive to indirect searches.