Discrete Changes Research Articles

QRFP43 modulates the activity of the hypothalamic-pituitary-thyroid axis in female sheep

Since the early discovery of QRFP43, intensive research has been primarily focused on its role in the modulation of food intake. As is widely recognised, the regulation of the body’s energy status is a highly complex process involving numerous systems, hormones and neurotransmitters. Among the most important regulators of energy status, alongside the satiety and hunger centre located in the hypothalamus, is the HPT axis, which directly and indirectly affects the regulation of metabolism in all cells of the body. Therefore, it seems highly important to conduct studies aimed at elucidating how QRFP43 may impact the secretory activity of the HPT axis. The objective of this work was to investigate the role of QRFP43 in modulating HPT axis activity in sheep. The study examined mRNA and peptide expression of TRH and TSH in the hypothalamus and pituitary, as well as plasma concentrations of TSH, free T4 (FT4) and free T3 (FT3). Moreover, the relationship between QRFP34 and mRNA expression of the Dio1, Dio2, and Dio3 genes was explored in selected tissues of the HPT axis. The animals (n = 48) were randomly divided into three experimental groups: a control group receiving an ICV infusion of Ringer-Locke solution, and two experimental groups receiving ICV infusions of QRFP43 at doses of 10 and 50 µg per day. Four 50-minute ICV infusions were administered to all sheep at 30 min intervals each of three consecutive days. Hypothalamic, pituitary and thyroid glands were collected and preserved for further immunohistochemical and molecular biological analyses. Additionally, blood samples were collected during the experiment for subsequent RIA determinations. In summary, the results of the experiment have indicated that QRFP43 modulates the secretory activity of the HPT axis at all organisational levels. Moreover, QRFP43 can alter the mRNA expression profiles of DIO1, DIO2 and DIO3 in HPT tissues, leading to discrete changes in the metabolism of the cells studied and their response to signals transmitted by T4 and T3.

Kin Competition Drives the Evolution of Earlier Metamorphosis.

Metamorphosis, the discrete morphological change between postembryonic life stages, is widespread across the animal kingdom. The suggested advantages of metamorphosis have usually been framed in terms of population benefits, i.e., ecological explanations. In contrast, evolutionary explanations concern whether and how metamorphosis spreads through a population owing to individual-fitness benefits. However, how kin selection modulates evolution of metamorphosis remains to be investigated formally. Here we develop a mathematical model to investigate how kin selection shapes the optimal timing of metamorphosis from foraging, non-reproductive larva to reproductive adult, when larvae tend to cluster with their genetic relatives. We consider the full range of larval competition intensities-from no competition to full competition-and the full range of relatedness coefficients-from unrelated to clonality. We provide testable predictions as to how kin selection modulates the timing of metamorphosis, as well as a conceptual framework within which empirical observations may be understood.

Eye pupils mirror information divergence in approximate inference

Pupil dilation is considered to track the arousal state linked to a wide range of cognitive processes. A recent article suggested the potential to unify findings in pupillometry studies based on an information theory framework and Bayesian methods. However, Bayesian methods become computationally intractable in many realistic situations. Thus, the present study examined whether pupil responses reflect the amount of information quantified in approximate inference, a practical method in a complex environment. We measured the pupil diameters of 27 healthy adults instructed to predict each subsequent number to be presented in a series, and to update their predictions at several discrete change points when an outcome generation criterion changed. Individual differences in task performance and pupil response were modeled by a variational Bayes method, which quantified prediction uncertainty and change point probability as Kullback-Leibler divergence (DKL) and Shannon’s surprise (SS). This model-based approach revealed that covariance between trial-wise pupil dilation and trial-wise DKL varies depending on prediction accuracy. Further, SS was sensitive to several discrete change points. These findings suggest that the pupil-linked arousal system reflects information divergence during approximate inference in a dynamic environment.

Efficient Importance Variational Approximations for State Space Models

Variational methods are a potentially scalable estimation approach for state space models. However, existing methods are inaccurate or computationally infeasible for many state space models. This article proposes a variational approximation that is accurate and fast for any model with a closed-form measurement density function and a state transition distribution within the exponential family of distributions. Our approach constructs a variational approximation to the states that is close to the exact conditional posterior distribution of the states using insights from the efficient importance sampling literature. We show that our method can accurately and quickly estimate a multivariate Skellam stochastic volatility model with high-frequency tick-by-tick discrete price changes of four stocks.

Single-cell transcriptomic and neuropathologic analysis reveals dysregulation of the integrated stress response in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a sporadic neurodegenerative tauopathy variably affecting brainstem and cortical structures, and characterized by tau inclusions in neurons and glia. The precise mechanism whereby these protein aggregates lead to cell death remains unclear. To investigate the contribution of these different cellular abnormalities to PSP pathogenesis, we performed single-nucleus RNA sequencing (snRNA-seq) and analyzed 50,708 high quality nuclei targeting the diencephalon, including the subthalamic nucleus and adjacent structures, from human post-mortem PSP brains with varying degrees of pathology compared to controls. Cell-type-specific differential expression and pathway analysis identified both common and discrete changes in numerous pathways previously implicated in PSP and other neurodegenerative disorders. This included EIF2 signaling, an adaptive pathway activated in response to diverse stressors, which was activated in multiple vulnerable cell types and validated in independent snRNA-seq and bulk RNA-seq datasets. Using immunohistochemistry, we found that activated eIF2α was positively correlated with tau pathology burden in vulnerable brain regions. Multiplex immunofluorescence localized activated eIF2α positivity to hyperphosphorylated tau (p-tau) positive neurons and ALDH1L1-positive astrocytes, supporting the increased transcriptomic EIF2 activation observed in these vulnerable cell types. In conclusion, these data provide insights into cell-type-specific pathological changes in PSP and support the hypothesis that failure of adaptive stress pathways play a mechanistic role in the pathogenesis and progression of PSP.

Light touch alters vestibular-evoked balance responses: insights into dynamics of sensorimotor reweighting.

Integrated multisensory feedback plays a crucial role in balance control. Minimal fingertip contact with a surface (light touch), reduces the center of pressure (CoP) by adding sensory information about postural orientation and balance state. Electrical vestibular stimulation (EVS) can increase sway by adding erroneous vestibular cues. This juxtaposition of conflicting sensory cues can be exploited to explore the dynamics of sensorimotor adaptations. We used continuous stochastic EVS (0-25 Hz; ±4 mA; 200-300 s) to evoke balance responses in CoP (experiment 1, experiment 2). Systems analyses (coherence, gain) quantified coupling and size of balance responses to EVS. We had participants either touch (TOUCH; <2 N) or not touch (NO-TOUCH) a load cell during EVS (experiment 1, experiment 2), or we intermittently removed the touch surface (experiment 2) to measure the effects of light touch on vestibular-evoked balance responses. We hypothesized that coherence and gain between EVS and CoP would decrease, consistent with the central nervous system (CNS) down-weighting vestibular cues that conflict with light touch. Light touch reduced CoP displacement but increased variation in the CoP signal explained by EVS input. Significant coherence between EVS and CoP was observed up to ∼30 Hz in both conditions but was significantly greater in the TOUCH condition from 12 to 28.5 Hz. Conversely, EVS-CoP gain was 63% lower in TOUCH compared with NO-TOUCH. Our findings show that light touch can reduce the size of vestibular-evoked responses but also increase high-frequency vestibular contributions for sway. This suggests that the CNS can use discrete changes in sensory inputs to alter balance behavior but cannot fully suppress responses to a potent cue.NEW & NOTEWORTHY This study reveals that minimal fingertip contact (light touch) during balance tasks not only diminishes the impact of electrical vestibular stimulation (EVS) on sway but also exposes a high-frequency center of pressure element, correlated to vestibular inputs, not typically seen in free standing. Specifically, light touch decreases the magnitude of EVS-induced sway while increasing coherence with EVS at higher frequencies. This illustrates the central nervous system's capacity to adaptively reweight sensorimotor processes for balance control.

Functionally graded material for improved wear resistance manufactured by directed energy deposition

AbstractProtecting components against wear and corrosion is a common way to improve their lifetime. This can be achieved by coating them with a hardfacing material. Common coatings consist of materials such as tungsten carbide or cobalt-chromium alloys, also known as Stellite. Hardfacing materials can be deposited by welding methods like plasma welding or laser cladding. The discrete change of the base material to the hardfacing layer can lead to cracks and chipping. Studies showed a reduced risk of cracking when a functionally graded material is used to create a smooth transition between the base and the hardfacing. Gradings from austenitic steel to cobalt-chromium alloys are already known in the literature. However, there is no knowledge about austenitic- ferritic duplex steels as base material. Therefore, this study aims to demonstrate the feasibility of a functionally graded material from duplex steel to cobalt-chromium alloy with a new approach. By using powder-based directed energy deposition, a graded material with smooth material transition is manufactured additively. Cracking and porosity are examined through metallography. Microhardness measurements as well as the analysis of the chemical composition by energy dispersive X-ray spectroscopy and X-ray fluorescence are used to validate the build-up strategy.

Protestant Elements in the Piers Plowman Texts of Robert Crowley and Takamiya MS 23

Abstract Recent studies of Robert Crowley’s editions of Piers Plowman emphasize Crowley’s fidelity to the manuscript tradition and efforts to produce an accurate and comprehensible text. The present article supports this assessment by comparing Crowley’s editions with New Haven, Beinecke Library, MS Takamiya 23 (olim Sion College, MS Arc. L.40. 2/E), a manuscript produced about the same time as the Crowley editions and closely related to Crowley’s principal exemplar. Censorship and other doctrinal alterations are infrequent in Takamiya 23 but unambiguous. While the great majority of unique readings have no evident motive beyond linguistic modernization, the Takamiya scribe also, in a few instances, harmonized the language of the medieval poem with sixteenth-century English Bibles and made discrete interpretative changes that sometimes align with Crowley’s outlook and sometimes seemingly depart from it. Another distinguishing feature of Takamiya 23 is the scribe’s apparent lack of interest in ‘prophetic’ passages, a salient focus of recent scholarship. For a more adequate account of the sixteenth-century reception of Piers Plowman, students may need to look beyond both ‘Protestantism’ and ‘prophecy’.

Solvation phenomena in ternary system tetramethylurea-methylacetamide-water: Insights from volumetric, compressibility and FTIR analysis

The properties of the ternary systems N,N,N',N'-tetramethylurea - N-methylacetamide - water were investigated using Fourier-transform infrared spectroscopy (FTIR), volumetric and compression measurements. Densities and sound velocities were determined in order to obtain the apparent molar volumes (VΦ) and apparent molar isentropic compressions (▪S,Φ). These values were then extrapolated to infinite dilution. Additionally, interaction parameters were calculated from the McMillan-Mayer theory. The studies were conducted at 288.15, 298.15, and 308.15 K, at atmospheric pressure (0.1 MPa). The concentration ranges of N-methylacetamide were 2, 4, 6, and 8 moles per kilogram of pure water, and for N,N,N',N'-tetramethylurea from 0 to around 0.35 moles per kilogram of solvent. Discrete changes in isentropic compression were observed. This is the result of the alignment of plots of ▪S,Φ0 as a function of NMA concentration. The results for N,N,N',N'-tetramethylurea were compared with analogous data for the system containing n-butylurea, which is an isomeric compound but exhibits different hydration behaviour. Additionally, large volumetric interaction coefficients were observed, indicating strong interactions between urea derivatives and NMA. This suggests the possibility of strong interactions between protein destabilizers and the protein backbone, differing from those observed for protein structure stabilizers. The observation contributes to understanding the mechanism of osmolyte action and their influence on protein stability.

A General Framework to Describe Drilling Process States

Summary Automation and digitalization of drilling require shared knowledge about the state of the drilling process: Is the bit on-bottom drilling or is the string in-slips; is there an overpull or is there a formation fluid influx? The research question addressed here is whether it is possible to define clear, sharable, and usable definitions of what a drilling process state is, and an agreed method to calculate it. The method to define the drilling process state originates from the fact that a drilling operation can be described by a set of partial differential equations, respecting boundary conditions. Therefore, the set of possible discrete changes of boundary conditions defines the set of all possible drilling process states. The possible state values for each of these boundary conditions can be clearly defined by a set of logical expressions utilizing boundary values at the partial differential equations. Each boundary condition is called a microstate. If the set of microstates is linearly independent and complete, then the overall state of the drilling process is uniquely described by the state of each of the microstates. The boundary values are either measured or estimated using a digital twin of the drilling process. In either case, an uncertainty is associated with the boundary value. It is therefore possible to estimate the probability of being in one state or another for each of the microstates. This is an important property as often the actual state of the drilling process is uncertain. If several digital twins or measurements are available, it is also possible to use sensor fusion to update the uncertainty of the boundary value. A common drilling process interpretation engine and well-defined drilling process states may help with the coordination of multiple advisors participating in the control of the drilling process. An example is given showing how an event-based drill-a-stand procedure involving several external advisors is automatically executed using a common source for the interpretation of the drilling process state. A shared definition and method of calculation of the drilling process state is a fundamental element of an infrastructure to enable interoperability at the rigsite. This work is part of the Drilling and Wells Interoperability Standard (D-WIS) initiative. D-WIS is a cross-industry work group providing the industry with solutions facilitating interoperability of computer systems at the rigsite.

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors

IntroductionRenal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). MethodsWe identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. ResultsAt 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). ConclusionsVolume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

An intraday GARCH model for discrete price changes and irregularly spaced observations

An intraday GARCH model for discrete price changes and irregularly spaced observations

Comprehensive Analysis of Input Shaping Techniques for a Chain Suspended from an Overhead Crane

Abstract This work investigates the use of input shaping techniques for controlling oscillations in a chain suspended from an overhead crane, aiming to enhance crane operations without sacrificing speed or safety. The study focuses on two specific input shaping strategies: step-input and polynomial-input shapers. The step-input shaper applies discrete changes at determined intervals, whereas the polynomial-input shaper utilizes a continuous function to adjust the crane's input throughout its operation. Numerical simulations assess the effectiveness of these techniques in reducing oscillations across various vibration modes of the chain and examine their impact on overall system performance metrics such as maneuver time, kinetic energy, robustness, and operational smoothness. Results from comprehensive simulations indicate that both input shapers significantly eliminated residual vibrations found in time-reduced inputs. The polynomial-input shaper demonstrated enhanced performance in decreasing the residual kinetic energy, and it promoted smoother operation and better adaptability to variations in chain length.

Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping

The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

A Late Devonian coelacanth reconfigures actinistian phylogeny, disparity, and evolutionary dynamics

The living coelacanth Latimeria (Sarcopterygii: Actinistia) is an iconic, so-called ‘living fossil’ within one of the most apparently morphologically conservative vertebrate groups. We describe a new, 3-D preserved coelacanth from the Late Devonian Gogo Formation in Western Australia. We assemble a comprehensive analysis of the group to assess the phylogeny, evolutionary rates, and morphological disparity of all coelacanths. We reveal a major shift in morphological disparity between Devonian and post-Devonian coelacanths. The newly described fossil fish fills a critical transitional stage in coelacanth disparity and evolution. Since the mid-Cretaceous, discrete character changes (representing major morphological innovations) have essentially ceased, while meristic and continuous characters have continued to evolve within coelacanths. Considering a range of putative environmental drivers, tectonic activity best explains variation in the rates of coelacanth evolution.

The Pathogenesis of CKD-Associated Pruritus: A Theoretical Model and Relevance for Treatment.

Our understanding of the pathogenesis of uremic pruritus (also known as CKD-associated pruritus [CKD-aP]) remains elusive. Although multiple discrete changes in the immunochemical milieu of the skin of patients with CKD-aP have been described, a coherent theory of mechanism is absent. This article proposes a theoretical model of mechanism. It concentrates on the initiation phase of CKD-aP and its three parts: ( 1 ) genesis, triggered by first precipitants; ( 2 ) cascade of cytokine release that follows and the cross-talking of multiple skin cells with each other and afferent nerve fibers; and ( 3 ) enhancement. The limitation of the model will be described and ideas for future research proposed. Implications for management shall be examined.

Dual nematode infection in Brassica nigra affects shoot metabolome and aphid survival in distinct contrast to single-species infection.

Previous studies showed that aphid performance was compromised on Brassica nigra infected by root-lesion nematodes (Pratylenchus penetrans, Pp), but less, or positively influenced by root-knot nematode (Meloidogyne spp.) infection. These experiments were on single-species nematode infections, but roots can be infected naturally with several nematode species simultaneously. We performed greenhouse assays to assess the effects of single [Meloidogyne incognita (Mi) or Pp] and concurrent (MP) nematode infections on aphid performance. Using targeted and untargeted profiling of leaf and phloem metabolomes, we examined how single and concurrent nematode infections affect shoot metabolomes, and elucidated the possible consequences for aphid performance. We found that the metabolic response to double-infection is different from that to single-species infections. Moreover, Mi and Pp infections triggered discrete changes in B. nigra leaf and phloem metabolic profiles. Both Pp and MP infections reduced aphid survival, suggesting that the biological effect could primarily be dominated by Pp-induced changes. This concurred with increased indole glucosinolates and hydroxycinnamic acid levels in the leaves, in particular the putative involvement of salicylic acid-2-O-β-d-glucoside. This study provides evidence that concurrent infection by different nematode species, as is common in natural environments, is associated with distinct changes in aboveground plant metabolomes, which are linked to differences in the survival of an aboveground herbivore.

Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping.

The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

The variable radio jet of the accreting neutron star the Rapid Burster

ABSTRACT The Rapid Burster is a unique neutron star low-mass X-ray binary system, showing both thermonuclear v-I and accretion-driven Type-II X-ray bursts. Recent studies have demonstrated how coordinated observations of X-ray and radio variability can constrain jet properties of accreting neutron stars – particularly when the X-ray variability is dominated by discrete changes. We present a simultaneous very large array, Swift, and INTErnational Gamma-Ray Astrophysics Laboratory observing campaign of the Rapid Burster to investigate whether its jet responds to Type-II bursts. We observe the radio counterpart of the X-ray binary at its faintest-detected radio luminosity, while the X-ray observations reveal prolific, fast X-ray bursting. A time-resolved analysis reveals that the radio counterpart varies significantly between observing scans, displaying a fractional variability of $38 \pm 5$ per cent. The radio faintness of the system prevents the robust identification of a causal relation between individual Type-II bursts and the evolution of the radio jet. However, based on a comparison of its low-radio luminosity with archival Rapid Burster observations and other accreting neutron stars, and on a qualitative assessment of the X-ray and radio light curves, we explore the presence of a tentative connection between bursts and jet: i.e. the Type-II bursts may weaken or strengthen the jet. The former of those two scenarios would fit with magnetorotational jet models; we discuss three lines of future research to establish this potential relation between Type-II bursts and jets more confidently.

Dynamic Euclidean bottleneck matching

A fundamental question in computational geometry is for a set of input points in the Euclidean space, that is subject to discrete changes (insertion/deletion of points at each time step), whether it is possible to maintain an exact/approximate minimum weight perfect matching and/or bottleneck matching (a perfect matching that minimizes the length of the longest matched edge), in sublinear update time. In this work, we answer this question in the affirmative for points on a real line and for points in the plane with a bounded geometric spread.For a set P of n points on a line, we show that there exists a dynamic algorithm that maintains an exact bottleneck matching of P and supports insertion and deletion in O(log⁡n) time. Moreover, we show that a modified version of this algorithm maintains an exact minimum-weight perfect matching with O(log⁡n) update (insertion and deletion) time. Next, for a set P of n points in the plane, we show that a (62)-factor approximate bottleneck matching of Pk, at each time step k, can be maintained in O(log⁡Δ) amortized time per insertion and O(log⁡Δ+|Pk|) amortized time per deletion, where Δ is the geometric spread of P (the ratio between the diameter of P and the distance between the closest pair of points in P).