Feedback Regulation and its Efficiency in Biochemical Networks

Intracellular biochemical networks fluctuate dynamically due to various internal and external sources of fluctuation. Dissecting the fluctuation into biologically relevant components is important for understanding how a cell controls and harnesses noise and how information is transferred over apparently noisy intracellular networks. While substantial theoretical and experimental advancement on the decomposition of fluctuation was achieved for feedforward networks without any loop, we still lack a theoretical basis that can consistently extend such advancement to feedback networks. The main obstacle that hampers is the circulative propagation of fluctuation by feedback loops. In order to define the relevant quantity for the impact of feedback loops for fluctuation, disentanglement of the causally interlocked influence between the components is required. In addition, we also lack an approach that enables us to infer non-perturbatively the influence of the feedback to fluctuation as the dual reporter system does in the feedforward network. In this work, we resolve these problems by extending the work on the fluctuation decomposition and the dual reporter system. For a single-loop feedback network with two components, we define feedback loop gain as the feedback efficiency that is consistent with the fluctuation decomposition for feedforward networks. Then, we clarify the relation of the feedback efficiency with the fluctuation propagation in an open-looped FF network. Finally, by extending the dual reporter system, we propose a conjugate feedback and feedforward system for estimating the feedback efficiency only from the statistics of the system non-perturbatively

A model of competition among more than two languages

We extend the Abrams-Strogatz model for competition between two languages [Nature 424, 900 (2003)] to the case of n(>=2) competing states (i.e., languages). Although the Abrams-Strogatz model for n=2 can be interpreted as modeling either majority preference or minority aversion, the two mechanisms are distinct when n>=3. We find that the condition for the coexistence of different states is independent of n under the pure majority preference, whereas it depends on n under the pure minority aversion. We also show that the stable coexistence equilibrium and stable monopoly equilibria can be multistable under the minority aversion and not under the majority preference. Furthermore, we obtain the phase diagram of the model when the effects of the majority preference and minority aversion are mixed, under the condition that different states have the same attractiveness. We show that the multistability is a generic property of the model facilitated by large n.Comment: 28 pages, 7 figure

Accelerator based epithermal neutron source for clinical boron neutron capture therapy

The world’s first accelerator based epithermal neutron source for clinical boron neutron capture therapy (BNCT) was designed, developed, and commissioned between 2008 and 2010 by Sumitomo Heavy Industries in collaboration with Kyoto University at the Kyoto University Institute for Integrated Radiation and Nuclear Science. The accelerator system is cyclotron-based and accelerates a proton up to an energy of approximately 30 MeV. The proton strikes a beryllium target, which produces fast neutrons that traverse a beam shaping assembly composed of a combination of lead, iron, aluminum, and calcium fluoride to reduce the neutron energy down to the epithermal range (∼10 keV) suitable for BNCT. The system is designed to produce an epithermal neutron flux of up to 1.4 × 10 9 n · cm − 2 · s − 1 (exiting from the moderator of a 12 cm diameter collimator) with a proton current of 1 mA. In 2017, the same type of accelerator was installed at the Kansai BNCT Medical Center and in March 2020 the system received medical device approval in Japan (Sumitomo Heavy Industries, NeuCure® BNCT system). Soon after, BNCT for unresectable, locally advanced, and recurrent carcinoma of the head and neck region was approved by the Japanese government for reimbursement covered by the national health insurance system

Improvement in the neutron beam collimation for application in boron neutron capture therapy of the head and neck region

In June 2020, the Japanese government approved boron neutron capture therapy for the treatment of head and neck cancer. The treatment is usually performed in a single fraction, with the neutron irradiation time being approximately 30–60 min. As neutrons scatter in air and loses its intensity, it is preferable to bring the patient as close to the beam port as possible to shorten the irradiation time. However, this can be a challenge, especially for patients with head and neck cancer, as the shoulders are an obstacle to a clean positioning. In this study, a novel neutron collimation system for an accelerator based neutron source was designed to allow for a more comfortable treatment, without compromising the irradiation time. Experimental measurements confirmed the simulation results and showed the new collimator can reduce the irradiation time by approximately 60% (under the same condition where the distance between the source and the patient surface was kept the same). The dose delivered to the surrounding healthy tissue was reduced with the new collimator, showing a 25% decrease in the D₅₀ of the mucosal membrane. Overall, the use of the newly designed collimator will allow for a more comfortable treatment of the head and neck region, reduce the treatment time, and reduce the dose delivered to the surrounding healthy tissue