First person – Masashi Nambu

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Masashi Nambu is first author on ‘ Direct evaluation of cohesin-mediated sister kinetochore associations at meiosis I in fission yeast’, published in JCS. Masashi works in the lab of Ayumu Yamamoto at Faculty of Science, and Graduate School of Integrated Science and Technology, Shizuoka University, Japan, investigating the development of ‘direct’ evaluation of kinetochore association and the contribution of cohesion and its regulators.

Evaluating the Response Time of an Optical Gas Sensor Based on Gasochromic Nanostructures

We propose a method for determining complex dielectric permittivity dynamics in the gasochromic oxides in the course of their interaction with a gas as well as for estimating the diffusion coefficient into a gasochromic oxide layer. The method is based on analysis of a time evolution of reflection spectra measured in the Kretschmann configuration. The method is demonstrated with a hydrogen-sensitive trilayer including an Au plasmonic film, WO3 gasochromic oxide layer, and Pt catalyst. Angular dependences of the reflectance as well as transmission spectra of the trilayer were measured in series at a constant flow of gas mixtures with hydrogen concentrations in a range of 0–0.36%, and a detection limit below 40 ppm (0.004%) of H2 was demonstrated. Response times to hydrogen were found in different ways. We show that the dielectric permittivity dynamics of WO3 must be retrieved in order to correctly evaluate the response time, whereas a direct evaluation from intensity changes for chosen wavelengths may have a high discrepancy. The proposed method gives insight into the optical properties dynamics for sensing elements based on gasochromic nanostructures.

THE DIRECT EVALUATION METHOD OF DEAD SHIP STABILITY FOR INTACT SHIP

The International Maritime Organization is currently establishing second generation intact stability criteria, the dead ship stability is considered one important criterion, so the development of its direct stability assessment regulation has become a topic undergoing close review. In this paper a peak-over-threshold (POT) method is proposed to evaluate the dead ship stability, which focuses on the statistical extrapolation that exceed the threshold, also the traditional Monte Carlo simulation is carried out to approve the method. On the basis of verification calculation of the sample ship CEHIPAR2792, the capsizing probability of a certain warship is also conducted. Moreover, the influence of initial stability height GM and effective wave slope coefficient Y on the capsizing probability is analysed. The results and the possible reason for the difference are examined. This study is expected to provide technical support for the second-generation stability criteria and establish the capsizing probability of damaged dead ship stability.

Direct evaluation of cohesin-mediated sister kinetochore associations at meiosis I in fission yeast

Kinetochores drive chromosome segregation by mediating chromosome interactions with the spindle. In higher eukaryotes, sister kinetochores are separately positioned on opposite sides of sister centromeres during mitosis, but associate with each other during meiosis I. Kinetochore association facilitates the attachment of sister chromatids to the same pole, enabling the segregation of homologous chromosomes toward opposite poles. In the fission yeast, Schizosaccharomyces pombe, Rec8-containing meiotic cohesin is suggested to establish kinetochore associations by mediating cohesion of the centromere cores. However, cohesin-mediated kinetochore associations on intact chromosomes have never been demonstrated directly. Here, we describe a novel method for the direct evaluation of kinetochore associations on intact chromosomes in live S. pombe cells, and demonstrate that sister kinetochores and the centromere cores are positioned separately on mitotic chromosomes but associate with each other on meiosis I chromosomes. Furthermore, we demonstrate that kinetochore association depends on meiotic cohesin and the cohesin regulators, Moa1 and Mrc1, and requires mating-pheromone signaling for its establishment. These results confirm cohesin-mediated kinetochore association and its regulatory mechanisms, along with the usefulness of the developed method for its analysis.

Spatial-temporal analysis of nanoparticles in live tumor spheroids impacted by cell origin and density

Nanoparticles hold great preclinical promise in cancer therapy but continue to suffer attrition through clinical trials. Advanced, three dimensional (3D) cellular models such as tumor spheroids can recapitulate elements of the tumor environment and are considered the superior model to evaluate nanoparticle designs. However, there is an important need to better understand nanoparticle penetration kinetics and determine how different cell characteristics may influence this nanoparticle uptake. A key challenge with current approaches for measuring nanoparticle accumulation in spheroids is that they are often static, losing spatial and temporal information which may be necessary for effective nanoparticle evaluation in 3D cell models. To overcome this challenge, we developed an analysis platform, termed the Determination of Nanoparticle Uptake in Tumor Spheroids (DONUTS), which retains spatial and temporal information during quantification, enabling evaluation of nanoparticle uptake in 3D tumor spheroids. Outperforming linear profiling methods, DONUTS was able to measure silica nanoparticle uptake to 10 μm accuracy in both isotropic and irregularly shaped cancer cell spheroids. This was then extended to determine penetration kinetics, first by a forward-in-time, center-in-space model, and then by mathematical modelling, which enabled the direct evaluation of nanoparticle penetration kinetics in different spheroid models. Nanoparticle uptake was shown to inversely relate to particle size and varied depending on the cell type, cell stiffness and density of the spheroid model. The automated analysis method we have developed can be applied to live spheroids in situ, for the advanced evaluation of nanoparticles as delivery agents in cancer therapy.

Labor Noncompete Agreements: Tool for Economic Efficiency or Means to Extract Value from Workers?

A number of theoretical arguments have been offered in favor of noncompete provisions in labor agreements. While there has been considerable empirical research on the effects of those provisions, there has been little direct evaluation of the arguments themselves. In this article, I lay out and evaluate three commonly heard arguments, namely, (1) the voluntary nature of labor agreements justifies a strong inference that the terms of those agreements, including noncompete provisions, are beneficial for both workers and firms and that they are economically efficient, 2( A) noncompetes facilitate efficient knowledge transfer from firms to workers, and 2( B) noncompetes encourage efficient firm-sponsored investment in worker training. These arguments, though not entirely without merit, mostly do not survive close scrutiny, and in fact such scrutiny reveals strong arguments that point in the opposite direction. In addition, noncompetes may cause important additional harms that are not measured in conventional economic research.

Strong evidence for genotype–phenotype correlations in Phelan-McDermid syndrome: Results from the developmental Synaptopathies consortium

Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of developmental, medical, cognitive, and behavioral abnormalities. Previous literature has begun to elucidate genotype–phenotype associations that may contribute to the wide spectrum of features. Here, we report results of genotype–phenotype associations in a cohort of 170 individuals with PMS. Genotypes were defined as Class I deletions (include SHANK3 only or SHANK3 with ARSA and/or ACR and RABL2B), Class II deletions (all other deletions), or sequence variants. Phenotype data were derived prospectively from direct evaluation, caregiver interview and questionnaires, and medical history. Analyses revealed individuals with Class I deletions or sequence variants had fewer delayed developmental milestones and higher cognitive ability compared to those with Class II deletions but had more skill regressions. Individuals with Class II deletions were more likely to have a variety of medical features, including renal abnormalities, spine abnormalities, and ataxic gait. Those with Class I deletions or sequence variants were more likely to have psychiatric diagnoses including bipolar disorder, depression, and schizophrenia. Autism spectrum disorder diagnoses did not differ between groups. This study represents the largest and most rigorous genotype–phenotype analysis in PMS to date and provides important information for considering clinical functioning, trajectories, and comorbidities as a function of specific genetic alteration.

Stochastic Generalized Active Space Self-Consistent Field: Theory and Application

An algorithm to perform stochastic generalized active space calculations, Stochastic-GAS, is presented, that uses the Slater determinant based FCIQMC algorithm as configuration interaction eigensolver. Stochastic-GAS allows the construction and stochastic optimization of preselected truncated configuration interaction wave functions, either to reduce the computational costs of large active space wave function optimizations, or to probe the role of specific electron correlation pathways. As for the conventional GAS procedure, the preselection of the truncated wave function is based on the selection of multiple active subspaces while imposing restrictions on the interspace excitations. Both local and cumulative minimum and maximum occupation number constraints are supported by Stochastic-GAS. The occupation number constraints are efficiently encoded in precomputed probability distributions, using the precomputed heat bath algorithm, which removes nearly all runtime overheads of GAS. This strategy effectively allows the FCIQMC dynamics to a priori exclude electronic configurations that are not allowed by GAS restrictions. Stochastic-GAS reduced density matrices are stochastically sampled, allowing orbital relaxations via Stochastic-GASSCF, and direct evaluation of properties that can be extracted from density matrices, such as the spin expectation value. Three test case applications have been chosen to demonstrate the flexibility of Stochastic-GAS: (a) the Stochastic-GASSCF optimization of a stack of five benzene molecules, that shows the applicability of Stochastic-GAS towards fragment-based chemical systems; (b) an uncontracted stochastic MRCISD calculation that correlates 96 electrons and 159 molecular orbitals, and uses a large (32, 34) active space reference wave function for an Fe(II)-porphyrin model system, showing how GAS can be applied to systematically recover dynamic electron correlation, and how in the specific case of the Fe(II)-porphyrin dynamic correlation further differentially stabilizes the triplet over the quintet spin state; (c) the study of an Fe4S4 cluster's spin-ladder energetics via highly truncated stochastic-GAS wave functions, where we show how GAS can be applied to understand the competing spin-exchange and charge-transfer correlating mechanisms in stabilizing different spin-states.