Explicitly Multi-Modal Benchmarks for Multi-Objective Optimization

In multi-objective optimization, designing good benchmark problems is an important issue for improving solvers. Although many benchmark problems have been proposed and some of them became de facto standards, designing multimodal problems that have a controllable landscape is still an open problem especially for high-dimensional cases. We thus propose the Benchmark with Explicit Multimodality (BEM), which lets the benchmark designer specify the basins of attraction using a graph structure known as the reachability graph. In this article, we focus on the mathematical formulation of the BEM. We will see that the BEM has preferable characteristics such as (i) realizing user-specified local Pareto set, (ii) allowing high-dimensional design spaces and (iii) possessing nonseparability

Phenethyl iosothiocyanate activates leptin signaling

Obesity, a principal risk factor for the development of diabetes mellitus, heart disease, and hypertension, is a growing and serious health problem all over the world. Leptin is a weight-reducing hormone produced by adipose tissue, which decreases food intake via hypothalamic leptin receptors (Ob-Rb) and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates leptin signaling by dephosphorylating JAK2, and the increased activity of PTP1B is implicated in the pathogenesis of obesity. Hence, inhibition of PTP1B may help prevent and reduce obesity. In this study, we revealed that phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate in certain cruciferous vegetables, potently inhibits recombinant PTP1B by binding to the reactive cysteinyl thiol. Moreover, we found that PEITC causes the ligand-independent phosphorylation of Ob-Rb, JAK2, and STAT3 by inhibiting cellular PTP1B in differentiated human SH-SY5Y neuronal cells. PEITC treatment also induced nuclear accumulation of phosphorylated STAT3, resulting in enhanced anorexigenic POMC expression and suppressed orexigenic NPY/AGRP expression. We demonstrated that oral administration of PEITC to mice significantly reduces food intake, and stimulates hypothalamic leptin signaling. Our results suggest that PEITC might help prevent and improve obesity

Compact Design of Work Cell with Robot Arm and Positioning Table under a Task Completion Time Constraint

Abstract-A work cell is generally designed to achieve a high throughput and its size is typically viewed as contingent to component sizes. In this paper, we aim to design a compact work cell (spatial requirement) and to minimize its task completion time (temporal requirement) to a value set as a constraint. By doing so, a work cell occupies a minimal space and achieves its desired throughput. The work cell size is evaluated based on the size and the swept volume of components. This evaluation is important since a robot arm can have a very large swept volume depending on a given task. To satisfy the spatial and temporal requirements, we propose the integration of the base placement optimization, goal rearrangement, and motion coordination between the robot arm and the positioning table. Furthermore, we introduce two motion coordination schemes based on the spatial and temporal requirements. We showed the effectiveness of the proposed method through simulations

Synthesis of tertiary alkylphosphonate oligonucleotides through light-driven radical-polar crossover reactions

光エネルギーで新しい化学修飾核酸を合成 --核酸リン原子の第三級アルキル化に成功--. 京都大学プレスリリース. 2023-11-01.Chemical modification of nucleotides can improve the metabolic stability and target specificity of oligonucleotide therapeutics, and alkylphosphonates have been employed as charge-neutral replacements for naturally-occurring phosphodiester backbones in these compounds. However, at present, the alkyl moieties that can be attached to phosphorus atoms in these compounds are limited to methyl groups or primary/secondary alkyls, and such alkylphosphonate moieties can degrade during oligonucleotide synthesis. The present work demonstrates the tertiary alkylation of the phosphorus atoms of phosphites bearing two 2’-deoxynuclosides. This process utilizes a carbocation generated via a light-driven radical-polar crossover mechanism. This protocol provides tertiary alkylphosphonate structures that are difficult to synthesize using existing methods. The conversion of these species to oligonucleotides having charge-neutral alkylphosphonate linkages through a phosphoramidite-based approach was also confirmed in this study

Detection of the Far-infrared [O III] and Dust Emission in a Galaxy at Redshift 8.312: Early Metal Enrichment in the Heart of the Reionization Era

We present the Atacama Large Millimeter/submillimeter Array (ALMA) detection of the [O III] 88 $\mu$m line and rest-frame 90 $\mu$m dust continuum emission in a Y-dropout Lyman break galaxy (LBG), MACS0416_Y1, lying behind the Frontier Field cluster MACS J0416.1-2403. This [O III] detection confirms the LBG with a spectroscopic redshift of $z = 8.3118 \pm 0.0003$, making this object one of the furthest galaxies ever identified spectroscopically. The observed 850 $\mu$m flux density of $137 \pm 26$ $\mu$Jy corresponds to a de-lensed total infrared (IR) luminosity of $L_{\rm IR} = (1.7 \pm 0.3) \times 10^{11} L_{\odot}$ if assuming a dust temperature of $T_{\rm dust} = 50$ K and an emissivity index of $\beta = 1.5$, yielding a large dust mass of $4 \times 10^6 M_{\odot}$. The ultraviolet-to-far IR spectral energy distribution modeling where the [O III] emissivity model is incorporated suggests the presence of a young ($\tau_{\rm age} \approx 4$ Myr), star-forming (SFR $\approx 60 M_{\odot}$ yr$^{-1}$), moderately metal-polluted ($Z \approx 0.2 Z_{\odot}$) stellar component with a mass of $M_{\rm star} = 3 \times 10^8 M_{\odot}$. An analytic dust mass evolution model with a single episode of star-formation does not reproduce the metallicity and dust mass in $\tau_{\rm age} \approx 4$ Myr, suggesting a pre-existing evolved stellar component with $M_{\rm star} \sim 3 \times 10^9 M_{\odot}$ and $\tau_{\rm age} \sim 0.3$ Gyr as the origin of the dust mass.Comment: Accepted by ApJ. 18 pages, 10 figures, 5 table

The Hippo Signaling Pathway Components Lats and Yap Pattern Tead4 Activity to Distinguish Mouse Trophectoderm from Inner Cell Mass

Outside cells of the preimplantation mouse embryo form the trophectoderm (TE), a process requiring the transcription factor Tead4. Here, we show that transcriptionally active Tead4 can induce Cdx2 and other trophoblast genes in parallel in embryonic stem cells. In embryos, the Tead4 coactivator protein Yap localizes to nuclei of outside cells, and modulation of Tead4 or Yap activity leads to changes in Cdx2 expression. In inside cells, Yap is phosphorylated and cytoplasmic, and this involves the Hippo signaling pathway component Lats. We propose that active Tead4 promotes TE development in outside cells, whereas Tead4 activity is suppressed in inside cells by cell contact- and Lats-mediated inhibition of nuclear Yap localization. Thus, differential signaling between inside and outside cell populations leads to changes in cell fate specification during TE formation

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world