Alu repeats at the boundaries of regulatory elements shape the epigenetic environment of immune genes in T cells

Promoters and enhancers are sites of transcription initiation (TSSs) and carry active histone modifications, including H3K4me1, H3K4me3, and H3K27ac. Yet, the principles governing the boundaries of such regulatory elements are still poorly characterized. Alu elements are good candidates for a boundary function, being highly abundant in gene-rich regions, while essentially excluded from regulatory elements. Here, we show that the interval from the TSS to the first upstream Alu accommodates essentially all H3K4me3 marks, while excluding DNA methylation. In contrast, enhancer-enriched H3K4me1 and H3K27ac marks eventually cross the first-Alu limit, consistent with enhancer-annotation occasionally overlapping with Alu elements. Remarkably, the average length of TSS-to-first Alu intervals greatly varies in-between tissues, being longer in stem- and shorter in immune-cells. Shortest TSS-to-Alu intervals were observed at promoters active in T cells, particularly at immune genes, correlating with serendipitous RNA polymerase II transcription and accumulation of H3K4me1 signal at the first-Alu. At several T-cell first-Alus, the DNA methylation was further found to evolved with age, regressing from young to middle-aged, then recovering later in life. Thus, the first-Alu upstream of TSSs functions as a dynamic boundary for regulatory elements, initiating the upstream DNA-methylation landscape, while also participating in the recording of immune gene transcriptional events.

Multistability in a star network of Kuramoto-type oscillators with synaptic plasticity

We analyze multistability in a star-type network of phase oscillators with coupling weights governed by phase-difference-dependent plasticity. It is shown that a network with N leaves can evolve into $$2^N$$ 2 N various asymptotic states, characterized by different values of the coupling strength between the hub and the leaves. Starting from the simple case of two coupled oscillators, we develop an analytical approach based on two small parameters $$\varepsilon$$ ε and $$\mu$$ μ , where $$\varepsilon$$ ε is the ratio of the time scales of the phase variables and synaptic weights, and $$\mu$$ μ defines the sharpness of the plasticity boundary function. The limit $$\mu \rightarrow 0$$ μ → 0 corresponds to a hard boundary. The analytical results obtained on the model of two oscillators are generalized for multi-leaf star networks. Multistability with $$2^N$$ 2 N various asymptotic states is numerically demonstrated for one-, two-, three- and nine-leaf star-type networks.

In vivo dissection of a clustered-CTCF domain boundary reveals developmental principles of regulatory insulation

Vertebrate genomes organize into topologically associating domains (TADs), delimited by boundaries that insulate regulatory elements from non-target genes. However, how boundary function is established is not well understood. Here, we combine genome-wide analyses and transgenic mouse assays to dissect the regulatory logic of clustered-CTCF boundaries in vivo, interrogating their function at multiple levels: chromatin interactions, transcription and phenotypes. Individual CTCF binding sites (CBS) deletions revealed that the characteristics of specific sites can outweigh other factors like CBS number and orientation. Combined deletions demonstrated that CBS cooperate redundantly and provide boundary robustness. We show that divergent CBS signatures are not strictly required for effective insulation and that chromatin loops formed by non-convergently oriented sites could be mediated by a loop interference mechanism. Further, we observe that insulation strength constitutes a quantitative modulator of gene expression and phenotypes. Our results highlight the modular nature of boundaries and their control over developmental processes.

SEQUENTIAL MONITORING OF CHANGES IN DYNAMIC LINEAR MODELS, APPLIED TO THE U.S. HOUSING MARKET

We propose a sequential monitoring scheme to find structural breaks in dynamic linear models. The monitoring scheme is based on a detector and a suitably chosen boundary function. If the detector crosses the boundary function, a structural break is detected. We provide the asymptotics for the procedure under the null hypothesis of stability. The consistency of the procedure is also proved. We derive the asymptotic distribution of the stopping time under the change point alternative. Monte Carlo simulation is used to show the size and the power of our method under several conditions. As an example, we study the real estate markets in Boston and Los Angeles, and at the national U.S. level. We find structural breaks in the markets, and we segment the data into stationary segments. It is observed that the autoregressive parameter is increasing but stays below 1.

Brokerage at the science–policy interface: from conceptual framework to practical guidance

This article analyses the conceptual framework of brokerage at the science–policy interface as an important boundary function to support trusted and transparent government decision-making. Policymaking involves a broad range of considerations, but science advice and evidence is critical to help inform decisions. However, mechanisms for requesting and receiving advice from the scientific community are not straightforward, considering that the knowledge needed generally spans multiple disciplines of the natural and social sciences. Once evidence has been appropriately synthesized, there remains the need to ensure an effective and unbiased translation to the policy and political community. The concept of knowledge brokerage revolves around an understanding of the ontologies, cultures and languages of both the policy community and the science community, in order to effectively link the two bidirectionally. In practical terms, this means ensuring that the information needs of the former are understood, and that the type and form of information offered by the latter aligns with those needs. Ideally, knowledge brokers act at the interface between researchers/experts and decision-makers to present evidence in a way that informs policy options but does not determine policy development. Conceptually, negotiating this interface involves acknowledging that values are embedded in the scientific process and evidentiary synthesis, and in particular, in considering the inferential risks inherent in making evidence claims. Brokers are faced with navigating complex policy dynamics and balancing information asymmetries between research providers and users. Building on the conceptual analysis and examination of the nuances of brokerage observed in practice, we propose a set of guidelines to translate the concepts of brokerage to practical application.

Mapping of functional elements of the Fab-6 boundary involved in the regulation of the Abd-B hox gene in Drosophila melanogaster

The autonomy of segment-specific regulatory domains in the Bithorax complex is conferred by boundary elements and associated Polycomb response elements (PREs). The Fab-6 boundary is located at the junction of the iab-5 and iab-6 domains. Previous studies mapped it to a nuclease hypersensitive region 1 (HS1), while the iab-6 PRE was mapped to a second hypersensitive region HS2 nearly 3 kb away. To analyze the role of HS1 and HS2 in boundary we generated deletions of HS1 or HS1 + HS2 that have attP site for boundary replacement experiments. The 1389 bp HS1 deletion can be rescued by a 529 bp core Fab-6 sequence that includes two CTCF sites. However, Fab-6 HS1 cannot rescue the HS1 + HS2 deletion or substitute for another BX-C boundary – Fab-7. For this it must be combined with a PRE, either Fab-7 HS3, or Fab-6 HS2. These findings suggest that the boundary function of Fab-6 HS1 must be bolstered by a second element that has PRE activity.

Impact of rainfall variability on soybean yields in Southern Brazil

As the third soybean-producer state in Brazil, Rio Grande do Sul (RS) presents a known year-on-year unevenness for soybean production, mainly due to water availability. This study aimed to assess the weather effects, with special focus on rainfall during 25 soybean growing seasons and 11 producing regions around the State. Sites were divided into three Clusters according to soybean yield and the effect of El Niño Southern Oscillation (ENSO) was considered in association with soil water balance. Neutral ENSO phases occurred in 32% of the years, while El Niño and La Ninã occurring in 36% and 32% of the years, respectively. Seasons under El Niño normally present higher accumulated rainfall, whereas those under La Niña present a reduction. Data from neutral-year sites of Clusters B and C seems to be more disturbed. No season had statistical difference of rainfall among Clusters under Neutral conditions. In addition, thermal gradient in RS from October to January benefited sites of Cluster A. Interaction of soils with higher water-storage capacity and cooler temperature reduces the water consumption by soybeans, causing lower values of water deficiency. A boundary function relating soybean yield and rainfall displays the limit of 800 mm for significant yield increments, and such amounts of rainfall were only achieved in El Niño seasons. The combined effect of rainfall and soil type on soybean yield, represented by the actual soybean yields-water deficit relationship, led to water propitiate from -3.7 to -15.2 kg mm-1 ha-1. Decision-making on public policies and investments on the soybean industry can be supported from our results, either to better planning the investments on the soybean farming systems depending on the ENSO phase predictions, either to reduce the production risks in the region inherent to local weather.

Operator-Based Nonlinear Control for a Miniature Flexible Actuator Using the Funnel Control Method

Recently, the studies of soft actuators have been getting increased attention among various fields. Soft actuators are very safe for fragile objects and have an affinity to humans because they are composed of flexible materials. A miniature flexible actuator is a kind of pneumatically driven soft actuator. It has a bellowed shape and asymmetrical structure. This shape can generate a curling motion in two ways under positive and negative pressures with only one air tube. In the previous article, a control system using adaptive λ-tracking control was proposed. This control gain can become too large as time tends to infinity because the adaptive law exhibits a non-decreasing gain. To solve this problem, the funnel control method is proposed. The adaptive gain of this method not only increases but also decreases; however, the design scheme of the boundary function which is needed to decide on adaptive gain is not proposed here. In this article, an operator-based nonlinear control system’s design and the design scheme of the boundary function using an observer are proposed. Then, the effectiveness of the proposed method is verified by a simulation and an experiment.

The Informative Power of all Possible Linear Functionals and the Mean-Square Error in the Diccretization of Solutions of the Diriclet Problem for the Laplace Equation in the Circle

The Dirichlet problem for the Laplace equation in the case of a circle belongs to the classical ones and in various aspects has been the subject of study in various fields of mathematics. Among them are such topics as - "Boundary properties of analytic functions", in the study of which powerful methods of function theories were created and honed, - The Banach problem on the existence of a basis for a class of functions consisting of continuous in a closed circle and analytic in, - Numerical methods, since this problem as a mathematical model describes many real processes. In this article, we consider the discretization problem of solutions of the Dirichlet problem for the Laplace equation in a circle from finite numerical information obtained from the boundary function as a result of applying all possible linear functionals. The optimal order of discretization error is found and the corresponding optimal operator of discretization is constructed. The problem of constructing probabilistic measures on functional classes is also considered. Probabilistic measures on the Korobov 𝐸𝑟 (0, 2𝜋) and Nikolsky 𝐻𝑟 2 (0, 2𝜋) classes are introduced. Two-sided estimates of the mean-square error of discretization the solution of the problem by operator (𝑇𝑁 𝑓) (𝛼, 𝜃) are established.