Chronic Inflammation in the Epidermis: A Mathematical Model

The epidermal tissue is the outmost component of the skin that plays an important role as a first barrier system in preventing the invasion of various environmental agents, such as bacteria. Recent studies have identified the importance of microbial competition between harmful and beneficial bacteria and the diversity of the skin surface on our health. We develop mathematical models (M1 and M2 models) for the inflammation process using ordinary differential equations and delay differential equations. In this paper, we study microbial community dynamics via transcription factors, protease and extracellular cytokines. We investigate possible mechanisms to induce community composition shift and analyze the vigorous competition dynamics between harmful and beneficial bacteria through immune activities. We found that the activation of proteases from the transcription factor within a cell plays a significant role in the regulation of bacterial persistence in the M1 model. The competition model (M2) predicts that different cytokine clearance levels may lead to a harmful bacteria persisting system, a bad bacteria-free state and the co-existence of harmful and good bacterial populations in Type I dynamics, while a bi-stable system without co-existence is illustrated in the Type II dynamics. This illustrates a possible phenotypic switch among harmful and good bacterial populations in a microenvironment. We also found that large time delays in the activation of immune responses on the dynamics of those bacterial populations lead to the onset of oscillations in harmful bacteria and immune activities. The mathematical model suggests possible annihilation of time-delay-driven oscillations by therapeutic drugs.ope

17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer.

Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2), which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT) was found to induce 17β-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA) tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17β-HSD2 immunohistochemical status. We further examined the correlations between 17β-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17β-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17β-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17β-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17β-HSD2 in endometrial cancer

Nonfullerene Acceptors Bearing Spiro‐Substituted Bithiophene Units in Organic Solar Cells: Tuning the Frontier Molecular Orbital Distribution to Reduce Exciton Binding Energy

Wang Kai, Jinnai Seihou, Urakami Takumi, et al. Nonfullerene Acceptors Bearing Spiro‐Substituted Bithiophene Units in Organic Solar Cells: Tuning the Frontier Molecular Orbital Distribution to Reduce Exciton Binding Energy. Angewandte Chemie International Edition, e202412691 (2024); https://doi.org/10.1002/anie.202412691.The development of nonfullerene acceptors (NFAs), represented by ITIC, has contributed to improving the power conversion efficiency (PCE) of organic solar cells (OSCs). Although tuning the electronic structures to reduce the exciton binding energy (Eb) is considered to promote photocharge generation, a rational molecular design for NFAs has not been established. In this study, we designed and developed two ITIC-based NFAs bearing spiro-substituted bithiophene or biphenyl units (named SpiroT-DCI and SpiroF-DCI) to tune the frontier molecular orbital (FMO) distribution of NFAs. While the highest occupied molecular orbitals (HOMOs) of SpiroF-DCI and ITIC are delocalized in the main π-conjugated framework, the HOMO of SpiroT-DCI is distributed on the bithiophene unit. Reflecting this difference, SpiroT-DCI exhibits a smaller Eb than either SpiroF-DCI or ITIC, and exhibits greater external quantum efficiency in single-component OSCs. Furthermore, SpiroT-DCI shows improved PCEs for bulk-heterojunction OSCs with a donor of PBDB-T, compared with that of either SpiroT-DCI or ITIC. Time-resolved spectroscopy measurements show that the photo-induced intermolecular charge separation is effective even in pristine SpiroT-DCI films. This study highlights the introduction of spiro-substituted bithiophene units that are effective in tuning the FMOs of ITIC, which is desirable for reducing the Eb and improving the PCE in OSCs

Design report of the KISS-II facility for exploring the origin of uranium

One of the critical longstanding issues in nuclear physics is the origin of the heavy elements such as platinum and uranium. The r-process hypothesis is generally supported as the process through which heavy elements are formed via explosive rapid neutron capture. Many of the nuclei involved in heavy-element synthesis are unidentified, short-lived, neutron-rich nuclei, and experimental data on their masses, half-lives, excited states, decay modes, and reaction rates with neutron etc., are incredibly scarce. The ultimate goal is to understand the origin of uranium. The nuclei along the pathway to uranium in the r-process are in "Terra Incognita". In principle, as many of these nuclides have more neutrons than 238U, this region is inaccessible via the in-flight fragmentation reactions and in-flight fission reactions used at the present major facilities worldwide. Therefore, the multi-nucleon transfer (MNT) reaction, which has been studied at the KEK Isotope Separation System (KISS), is attracting attention. However, in contrast to in-flight fission and fragmentation, the nuclei produced by the MNT reaction have characteristic kinematics with broad angular distribution and relatively low energies which makes them non-amenable to in-flight separation techniques. KISS-II would be the first facility to effectively connect production, separation, and analysis of nuclides along the r-process path leading to uranium. This will be accomplished by the use of a large solenoid to collect MNT products while rejecting the intense primary beam, a large helium gas catcher to thermalize the MNT products, and an MRTOF mass spectrograph to perform mass analysis and isobaric purification of subsequent spectroscopic studies. The facility will finally allow us to explore the neutron-rich nuclides in this Terra Incognita.Comment: Editors: Yutaka Watanabe and Yoshikazu Hirayam

Detection of a bright burst from the repeating FRB 20201124A at 2 GHz

We present a detection of a bright burst from FRB 20201124A, which is one of the most active repeating FRBs, based on S-band observations with the 64-m radio telescope at the Usuda Deep Space Center/JAXA. This is the first FRB observed by using a Japanese facility. Our detection at 2 GHz in February 2022 is the highest frequency for this FRB and the fluence of $>$ 189 Jy ms is one of the brightest bursts from this FRB source. We place an upper limit on the spectral index $\alpha$ = -2.14 from the detection of the S band and non-detection of the X band at the same time. We compare an event rate of the detected burst with ones of the previous research, and suggest that the power-law of the luminosity function might be broken at lower fluence, and the fluences of bright FRBs distribute up to over 2 GHz with the power-law against frequency. In addition, we show the energy density of the burst detected in this work was comparable to the bright population of one-off FRBs. We propose that repeating FRBs can be as bright as one-off FRBs, and only their brightest bursts could be detected so some of repeating FRBs intrinsically might have been classified as one-off FRBs.Comment: 8 pages, 5 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

Dynamic nature of SecA and its associated proteins in Escherichia coli.

Mechanical properties such as physical constraint and pushing of chromosomes are thought to be important for chromosome segregation in Escherichia coli and it could be mediated by a hypothetical molecular "tether." However, the actual tether that mediates these features is not known. We previously described that SecA (Secretory A) and Secretory Y (SecY), components of the membrane protein translocation machinery, and AcpP (Acyl carrier protein P) were involved in chromosome segregation and homeostasis of DNA topology. In the present work, we performed three-dimensional deconvolution of microscopic images and time-lapse experiments of these proteins together with MukB and DNA topoisomerases, and found that these proteins embraced the structures of tortuous nucleoids with condensed regions. Notably, SecA, SecY, and AcpP dynamically localized in cells, which was interdependent on each other requiring the ATPase activity of SecA. Our findings imply that the membrane protein translocation machinery plays a role in the maintenance of proper chromosome partitioning, possibly through "tethering" of MukB [a functional homolog of structural maintenance of chromosomes (SMC) proteins], DNA gyrase, DNA topoisomerase IV, and SeqA (Sequestration A)

Dynamic nature of SecA and its associated proteins in Escherichia coli.

Mechanical properties such as physical constraint and pushing of chromosomes are thought to be important for chromosome segregation in Escherichia coli and it could be mediated by a hypothetical molecular tether. However, the actual tether that mediates these features is not known. We previously described that SecA (Secretory A) and SecY, components of the membrane protein translocation machinery, and AcpP (Acyl carrier protein P) were involved in chromosome segregation and homeostasis of DNA topology. In the present work we performed three-dimensional deconvolution of microscopic images and time-lapse experiments of these proteins together with MukB and DNA topoisomerases, and found that these proteins embraced the structures of tortuous nucleoids with condensed regions. Notably, SecA, SecY and AcpP dynamically localized in cells, which was interdependent on each other requiring the ATPase activity of SecA. Our findings imply that the membrane protein translocation machinery plays a role in the maintenance of proper chromosome partitioning, possibly through tethering of MukB (a functional homolog of structural maintenance of chromosomes [SMC] proteins), DNA gyrase, DNA topoisomerase IV and SeqA (Sequestration A)

Androgen receptor and intracrine androgen signaling in endometrial carcinomas

The androgen receptor (AR) is known to play critical roles in the malignancy of prostate cancer as well as the management of male reproductive organs. Endometrial carcinoma, one of the major female cancers, is considered an androgen-related cancer. However, the importance of androgen signaling through its receptor in endometrial carcinomas has not yet been clarified. We recently demonstrated the significance of androgen signaling and intracrine dihydrotestosterone (DHT) in endometrial carcinomas as follows: 1) A positive status of androgen receptor (AR) was significantly associated with high rates of progression-free survival (PFS), but not with endometrial cancer-specific survival (ECSS) in endometrial carcinoma patients; 2) The potent androgen DHT was synthesized from testosterone by 5α-reductase in endometrial carcinoma tissues; and 3) endometrial carcinoma patients that were AR/5α-reductase type 1 double-negative had significantly worse PFS and ECSS. These findings suggest that androgen signaling exerts anti-cancer effects through the intratumoral DHT-AR pathway in endometrial carcinomas. In this highlight article, we describe androgen signaling in endometrial carcinomas, focusing mainly on our recent study entitled “The role of 5α-reductase type 1 associated with intratumoral dihydrotestosterone concentrations in human endometrial carcinoma” and discuss the findings of some previous related studies

A Screening Method for Prevention of Ratcheting Strain Derived From Movement of Temperature Distribution

In this paper, we simplify the existing method and propose a screening method to prevent thermal ratcheting strain in the design of practical components. The proposed method consists of two steps to prevent the continuous accumulation of ratcheting strain. The first step is to determine whether all points through the wall thickness are in the plastic state. This is based on an equivalent membrane stress, which comprises the primary stress and the secondary membrane stress. When the equivalent stress exceeds the yield strength in some regions of the cylinder, the axial lengths of these regions are measured for the second step. The second step is to determine whether the accumulation of the plastic strain saturates. For this purpose, we define the screening criteria for the length of the area with full section yield state. When this length is sufficiently small, residual stress is generated in the direction opposite to the plastic deformation direction. As a result of residual stress, further accumulation of the plastic deformation is suppressed, and finally shakedown occurs. To validate the proposed method, we performed a set of elastoplastic finite element method (FEM) analyses, with the assumption of elastic perfectly plastic material. Not only did we investigate about the effect of the axial length of the area with full section yield state but also we investigated about effects of spatial distribution of temperature, existence of primary stress, and radius thickness ratio

People Copy Success More Than Failure in Social Learning

Social learning is a fundamental mechanism for efficiently transferring and coordinating norms, skills, and sophisticated cultural information to individuals. However, the psychological mechanisms underlying social learning remain unclear. To investigate this, we recruited adult participants ( N  = 103), who observed a model’s performance in a two-choice reward-searching task. Two cues were used to determine the reward, with both cues possessing an alternative signal that had a specific rule for finding the reward. Although the model succeeded with one cue but failed with another, both possessed equal information, which enabled the participants to find the reward. Participants were more likely to use the cue linked to the model’s success than the model’s failure when asked to solve the task by themselves. This “copy success” bias reflects the psychological process underlying social learning suggested by previous evolutionary theories and provides practical suggestions for efficient learning processes