Testable Model Research Articles

Parity and lepton masses in the left-right symmetric model

Curiously, in the minimal left right symmetric model chiral symmetry that protects the electron’s mass (me), due to parity (P), implies in the symmetry limit the vanishing of its neutrino mixing angles. We break the chiral symmetry softly (or spontaneously if it is gauged) to generate the observed large neutrino mixing angles at the tree-level. The electron then acquires its mass on renormalization group equation (RGE) running due to its neutrino’s mixing, and in turn determines the B−L gauge symmetry breaking scale (vR) to be 1010 GeV≲vR≤1015 GeV. If the muon’s mass is also generated radiatively, the B−L breaking scale is ∼1014−15 GeV. Regardless of the high scale of vR, this is a testable model since on RGE running and P breaking, a large strong CP phase (θ¯≫10−10) which depends logarithmically on vR is generated if there is O(1) CP violation in leptonic Yukawa couplings. Hence we expect that leptonic CP phases including the Dirac CP phase δCP of the PMNS matrix must be consistent with 0 or 180o to within a degree, which can be verified or excluded by neutrino experiments such as DUNE and Hyper-Kamiokande. In lieu of P, if charge conjugation C is used, the same results follow. However with C and no P, axions would likely need to be added anyway, in which case there is no constraint on δCP. Published by the American Physical Society 2024

Functional genomics of human skeletal development and the patterning of height heritability.

Underlying variation in height are regulatory changes to chondrocytes, cartilage cells comprising long-bone growth plates. Currently, we lack knowledge on epigenetic regulation and gene expression of chondrocytes sampled across the human skeleton, and therefore we cannot understand basic regulatory mechanisms controlling height biology. We first rectify this issue by generating extensive epigenetic and transcriptomic maps from chondrocytes sampled from different growth plates across developing human skeletons, discovering novel regulatory networks shaping human bone/joint development. Next, using these maps in tandem with height genome-wide association study (GWAS) signals, we disentangle the regulatory impacts that skeletal element-specific versus global-acting variants have on skeletal growth, revealing the prime importance of regulatory pleiotropy in controlling height variation. Finally, as height is highly heritable, and thus often the test case for complex-trait genetics, we leverage these datasets within a testable omnigenic model framework to discover novel chondrocyte developmental modules and peripheral-acting factors shaping height biology and skeletal growth.

Social media and youth mental health: Simple narratives produce biased interpretations.

Many academics and pundits contend that social media use is the primary cause of an international youth mental health crisis. However, these claims often rely on correlational evidence, ignoring the confounding effects of developmental, environmental, social, and psychological factors that influence mental health. This oversimplifies the complex etiology of mental health problems. We call for a more nuanced understanding of the role of social media in youth mental health that avoids oversimplification. Additionally, we urge researchers to move beyond vague, narrative-driven verbal theories and encode them into precise, testable causal models. Using simulation techniques and specification curve analyses, we show how misspecified models that ignore these confounding factors can lead to biased conclusions about social media's adverse effects. This simplistic focus on social media use diverts attention from the broader factors contributing to youth mental health problems, hindering the development of effective interventions and support. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Future invasion risk assessment of the peacock bass in Neotropical ecoregions: A conceptual and testable model

Protecting freshwater biodiversity from non-native invasive species and their impacts is crucial for minimising both regional and global deterioration of ecosystem services. The yellow peacock bass Cichla ocellaris, a predatory freshwater fish endemic to the Amazon region, has been translocated within several Neotropical ecoregions, exhibiting harmful effects on biodiversity. In order to facilitate the prioritization of management efforts, which are essential for defining conservation actions in extensive and diverse areas, we propose a risk assessment index that integrates multiple ecological and environmental variables within a comprehensive framework, here applied for C. ocellaris. By considering fish species richness, occurrence frequency, and climate suitability, our index provides a more nuanced understanding of invasion risks. Within regions categorized as high and very high risk, where ecological impacts of C. ocellaris have been extensively documented (e.g., the Southern and North-East Brazilian regions, as well as Central American and Caribbean ecoregions), numerous environments are increasingly conducive to the establishment of this invasive species, exacerbated by a surge in dam constructions. Our analysis projects a significant increase in suitable habitats by 5% to 6.5%, with Southern and Northeastern Brazil and Central America identified as critical zones. Thus, our reproducible risk assessment framework, which considers freshwater ecoregions as conservation units, not only directs effective resource allocation for control measures but also enhances our ability to predict and mitigate the ecological impacts of non-native species introductions, providing a valuable tool for both policymakers and conservationists.

Integrated testability modeling method of complex systems for fault feature selection and diagnosis strategy optimization

The efficacy of system fault diagnosis is intricately linked with the testability design of the system, particularly in intricate systems encompassing numerous components exhibiting diverse failure modes. However, current research shows a dearth of effective testability models and algorithms for generating diagnostic strategies in multi-valued attribute systems (MVAS) with uncertainty. To address this, the present paper introduces a novel method for testability modeling for complex systems. This approach incorporates signal features in lieu of raw sensor signals within the testability modeling process and accounts for the uncertainties surrounding test outcomes. The context of complex MVAS, characterized by inherent uncertainty, the paper proposes a novel method for constructing a four-value dependency matrix (D-matrix). Furthermore, the paper presents a novel sequential diagnosis strategy optimization approach based on a heuristic evaluation function for the multivalued D-matrix with uncertainty. The proposed methodology has been rigorously validated using a real-world case study involving an aero-engine fuel metering device system. Comparative experiments show that the proposed method can achieve better diagnostic performance in the shortest time.

Testability modeling of aeroengine and analysis optimization method based on improved correlation matrix

This paper aims to optimize the testability analysis method of aero-engines by presenting a testability modeling and an improved correlation matrix method. Because of strong coupling in aero-engines, the traditional testabilitsy modeling method based on graph theory is difficult to accurately express the relationship between faults and test points. Simulation technology can simulate actual work process of system. So this paper launches the research based on simulation model. Firstly, the gas path model is established according to the thermodynamic principle of aero-engines and accuracy of the model is verified. Secondly, common faults of gas path are selected. Affected parameters are obtained after injecting faults into the model, so as to obtain the relationship between faults and test points, that is, the correlation matrix. Then, after going through masses of simulations, it is found that the relationship between faults and test points can be divided into three categories: positive correlation, negative correlation and no correlation. The correlation matrix can be improved by diversifying its elements. During simulation, accuracy of the sensors are not considered. The correlation matrix is optimized with the accuracy of sensors in the gas path as a constraint, so that it is more in line with engineering practice. Finally, four testability characteristics and two testability metrics are defined, and the correlation matrix before and after improvement are analyzed and compared. It is found that the improved correlation matrix can isolate more faults on the premise of reducing test points, which proves the effectiveness of the proposed method.

On language, children and books / Sobre lenguaje, infancia y libros

Understanding how children learn requires three levels of evidence: observations, correlations and experiments. Observations are necessary to allow one to describe patterns of behaviours, while correlational research is necessary to establish that the observed patterns are not due to chance and therefore suggests that they may also exist in the population. A critical integration of the accumulated evidence is necessary to establish testable models of how children learn. Then, interventions, using experimental paradigms, are necessary to assess whether the models established from the two previous steps actually account for child learning. Herein, I described the research that my colleagues and I conducted on reading books to young children — research that addressed the three levels of evidence described above. I also reviewed findings on how digital books can potentially be used to promote language and comprehension skills. Prior to doing so, however, I described the path that led me to study how children learn language from shared reading experiences. The conclusion provides avenues for future research.

An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation

Adar null mutant mouse embryos die with aberrant double-stranded RNA (dsRNA)-driven interferon induction, and Adar Mavs double mutants, in which interferon induction is prevented, die soon after birth. Protein kinase R (Pkr) is aberrantly activated in Adar Mavs mouse pup intestines before death, intestinal crypt cells die, and intestinal villi are lost. Adar Mavs Eifak2 (Pkr) triple mutant mice rescue all defects and have long-term survival. Adenosine deaminase acting on RNA 1 (ADAR1) and PKR co-immunoprecipitate from cells, suggesting PKR inhibition by direct interaction. AlphaFold studies on an inhibitory PKR dsRNA binding domain (dsRBD)-kinase domain interaction before dsRNA binding and on an inhibitory ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA provide a testable model of the inhibition. Wild-type or editing-inactive human ADAR1 expressed in A549 cells inhibits activation of endogenous PKR. ADAR1 dsRNA binding is required for, but is not sufficient for, PKR inhibition. Mutating the ADAR1 dsRBD3-PKR contact prevents co-immunoprecipitation, ADAR1 inhibition of PKR activity, and co-localization of ADAR1 and PKR in cells.

Measuring and improving software testability at the design level

ContextThe quality of software systems is significantly influenced by design testability, an aspect often overlooked during the initial phases of software development. The implementation may deviate from its design, resulting in decreased testability at the integration and unit levels. ObjectiveThe objective of this study is to automatically identify low-testable parts in object-orientated design and enhance them by refactoring to design patterns. The impact of various design metrics mainly coupling (e.g., fan-in and fan-out) and inheritance (e.g., depth of inheritance tree and number of subclasses) metrics on design testability is measured to select the most appropriate refactoring candidates. MethodThe methodology involves creating a machine learning model for design testability prediction using a large dataset of Java classes, followed by developing an automated refactoring tool. The design classes are vectorized by ten design metrics and labeled with testability scores calculated from a mathematical model. The model computes testability based on code coverage and test suite size of classes that have already been tested via automatic tools. A voting regressor model is trained to predict the design testability of any class diagram based on these design metrics. The proposed refactoring tool for dependency injection and factory method is applied to various open-source Java projects, and its impact on design testability is assessed. ResultsThe proposed design testability model demonstrates its effectiveness by satisfactorily predicting design testability, as indicated by a mean squared error of 0.04 and an R2 score of 0.53. The automated refactoring tool has been successfully evaluated on six open-source Java projects, revealing an enhancement in design testability by up to 19.11 %. ConclusionThe proposed automated approach offers software developers the means to continuously evaluate and enhance design testability throughout the entire software development life cycle, mitigating the risk of testability issues stemming from design-to-implementation discrepancies.

Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.

Human mitochondria possess a multi-copy circular genome, mitochondrial DNA (mtDNA), that is essential for cellular energy metabolism. The number of copies of mtDNA per cell, and their integrity, are maintained by nuclear-encoded mtDNA replication and repair machineries. Aberrant mtDNA replication and mtDNA breakage are believed to cause deletions within mtDNA. The genomic location and breakpoint sequences of these deletions show similar patterns across various inherited and acquired diseases, and are also observed during normal ageing, suggesting a common mechanism of deletion formation. However, an ongoing debate over the mechanism by which mtDNA replicates has made it difficult to develop clear and testable models for how mtDNA rearrangements arise and propagate at a molecular and cellular level. These deletions may impair energy metabolism if present in a high proportion of the mtDNA copies within the cell, and can be seen in primary mitochondrial diseases, either in sporadic cases or caused by autosomal variants in nuclear-encoded mtDNA maintenance genes. These mitochondrial diseases have diverse genetic causes and multiple modes of inheritance, and show notoriously broad clinical heterogeneity with complex tissue specificities, which further makes establishing genotype-phenotype relationships challenging. In this review, we aim to cover our current understanding of how the human mitochondrial genome is replicated, the mechanisms by which mtDNA replication and repair can lead to mtDNA instability in the form of large-scale rearrangements, how rearranged mtDNAs subsequently accumulate within cells, and the pathological consequences when this occurs.

Developmental stasis, sensitivity, and disturbance: Linking concepts to analytic methods using impulsivity and alcohol use.

The goals of this article are to (a) describe and contrast conceptual characteristics of periods of developmental sensitivity, disturbance, and stasis, and (b) translate these concepts to testable analytic models with an example dataset. Although the concept of developmental sensitivity is widely known, the concepts of developmental stasis and disturbance have received less attention. We first define the concepts and their principles and then, using repeated measures data on impulsivity and alcohol use from adolescence to young adulthood, propose the dual latent change score (LCS) growth model as one analytic approach for evaluating evidence for key characteristics of these developmental concepts via examination of intraindividual time-varying associations.

Cosmological Test of an Ultraviolet Origin of Dark Energy

The accelerated expansion of the Universe is impressively well described by a cosmological constant. However, the observed value of the cosmological constant is much smaller than expected based on quantum field theories. Recent efforts to achieve consistency in these theories have proposed a relationship between Dark Energy and the most compact objects, such as black holes (BHs). However, experimental tests are very challenging to devise and perform. In this article, we present a testable model with no cosmological constant in which the accelerated expansion can be driven by black holes. The model couples the expansion of the Universe (the Friedmann equation) with the mass function of cosmological halos (using the Press–Schechter formalism). Through the observed link between halo masses and BH masses, one thus gets a coupling between the expansion rate of the Universe and the BHs. We compare the predictions of this simple BH model with SN1a data and find poor agreement with observations. Our method is sufficiently general to allow us to also test a fundamentally different model, also without a cosmological constant, where the accelerated expansion is driven by a new force proportional to the internal velocity dispersion of galaxies. Surprisingly enough, this model cannot be excluded using the SN1a data.

Post-COVID breathlessness: a mathematical model of respiratory processing in the brain

Breathlessness is among the most common post-COVID symptoms. In a considerable number of patients, severe breathlessness cannot be explained by peripheral organ impairment. Recent concepts have described how such persistent breathlessness could arise from dysfunctional processing of respiratory information in the brain. In this paper, we present a first quantitative and testable mathematical model of how processing of respiratory-related signals could lead to breathlessness perception. The model is based on recent theories that the brain holds an adaptive and dynamic internal representation of a respiratory state that is based on previous experiences and comprises gas exchange between environment, lung and tissue cells. Perceived breathlessness reflects the brain’s estimate of this respiratory state signaling a potentially hazardous disequilibrium in gas exchange. The internal respiratory state evolves from the respiratory state of the last breath, is updated by a sensory measurement of CO2 concentration, and is dependent on the current activity context. To evaluate our model and thus test the assumed mechanism, we used data from an ongoing rebreathing experiment investigating breathlessness in patients with post-COVID without peripheral organ dysfunction (N = 5) and healthy control participants without complaints after COVID-19 (N = 5). Although the observed breathlessness patterns varied extensively between individual participants in the rebreathing experiment, our model shows good performance in replicating these individual, heterogeneous time courses. The model assumes the same underlying processes in the central nervous system in all individuals, i.e., also between patients and healthy control participants, and we hypothesize that differences in breathlessness are explained by different weighting and thus influence of these processes on the final percept. Our model could thus be applied in future studies to provide insight into where in the processing cascade of respiratory signals a deficit is located that leads to (post-COVID) breathlessness. A potential clinical application could be, e.g., the monitoring of effects of pulmonary rehabilitation on respiratory processing in the brain to improve the therapeutic strategies.

A module for automatic analysis of burst spectra for consonant place detection

Widespread methods for automatic speech processing have become increasingly powerful, but they do not aim to model aspects of human speech processing. Previous research has shown that individual acoustic cues are important in human speech perception. Developing a model that is capable of identifying individual acoustic cues in speech enhances our ability to extract meaningful information from a speech signal, irrespective of speaker variations or phonemic differences, in a way that provides a transparent and testable model of human speech processing. This research investigates a module for automatic analysis of the spectral burst cue in fricative and plosive speech sounds. The method determines the place of articulation of the spectral burst by utilizing spectral moment measurements near locations where a spectral burst is likely to occur as features in a Gaussian mixture model. This research lays the groundwork for a dynamic model that is developed to be consistent with the Bayesian belief updating framework, in alignment with prior work in human speech perception.

Membrane lipids drive formation of KRAS4b-RAF1 RBDCRD nanoclusters on the membrane

The oncogene RAS, extensively studied for decades, presents persistent gaps in understanding, hindering the development of effective therapeutic strategies due to a lack of precise details on how RAS initiates MAPK signaling with RAF effector proteins at the plasma membrane. Recent advances in X-ray crystallography, cryo-EM, and super-resolution fluorescence microscopy offer structural and spatial insights, yet the molecular mechanisms involving protein-protein and protein-lipid interactions in RAS-mediated signaling require further characterization. This study utilizes single-molecule experimental techniques, nuclear magnetic resonance spectroscopy, and the computational Machine-Learned Modeling Infrastructure (MuMMI) to examine KRAS4b and RAF1 on a biologically relevant lipid bilayer. MuMMI captures long-timescale events while preserving detailed atomic descriptions, providing testable models for experimental validation. Both in vitro and computational studies reveal that RBDCRD binding alters KRAS lateral diffusion on the lipid bilayer, increasing cluster size and decreasing diffusion. RAS and membrane binding cause hydrophobic residues in the CRD region to penetrate the bilayer, stabilizing complexes through β-strand elongation. These cooperative interactions among lipids, KRAS4b, and RAF1 are proposed as essential for forming nanoclusters, potentially a critical step in MAP kinase signal activation.

Mini review: Asymmetric Müllerian duct development in the chicken embryo.

Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract. In humans, the Müllerian ducts differentiate into the Fallopian tubes, uterus and upper portion of the vagina. In birds and reptiles, the Müllerian ducts develop into homologous structures, the oviducts. The genetic and hormonal regulation of duct development is a model for understanding sexual differentiation. In males, the ducts typically undergo regression during embryonic life, under the influence of testis-derived Anti-Müllerian Hormone, AMH. In females, a lack of AMH during embryogenesis allows the ducts to differentiate into the female reproductive tract. In the chicken embryo, a long-standing model for development and sexual differentiation, Müllerian duct development in females in asymmetric. Only the left duct forms an oviduct, coincident with ovary formation only on the left side of the body. The right duct, together with the right gonad, becomes vestigial. The mechanism of this avian asymmetry has never been fully resolved, but is thought to involve local interplay between AMH and sex steroid hormones. This mini-review re-visits the topic, highlighting questions in the field and proposing a testable model for asymmetric duct development. We argue that current molecular and imaging techniques will shed new light on this curious asymmetry. Information on asymmetric duct development in the chicken model will inform our understanding of sexual differentiation in vertebrates more broadly.

Etonogestrel promotes respiratory recovery in an invivo rat model of central chemoreflex impairment.

The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes. We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography. Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery. This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.

Conceptualisation of Nation Brands to Attract Foreign Direct Investment: An Integrated Model

A nation brand is defined as a brand of a country. Nations are not only political and sovereign entities, but also business entities that conduct foreign trade, promote talent and innovation, create knowledge, levy taxes and enact laws. As a whole, nations accumulate wealth, power and status and leverage their brand identities to further their strategic interests. This article looks at the theories of nation branding and its implications on attracting foreign direct investment (FDI). FDI inflow has been studied by various researchers. The impact of nation branding on FDI has not been studied from an integrated perspective. This article analyses all the papers published in the field from 1969 when the genre of research was first mentioned in management literature and the factors presented by various researchers and place brand practitioners up to 2022 and combines them all into one integrated statistically testable model. The article analyses the factors from three perspectives—that of the governments and investment promotion agencies, external brand analysts and ranking consultancies as well as that of the investors.

Intramolecular bridging strategies to suppress two-phonon Raman spin relaxation in dysprosocenium single-molecule magnets.

Dy(III) bis-cyclopentadienyl (Cp) sandwich compounds exhibit extremely strong single-ion magnetic anisotropy which imbues them with magnetic memory effects such as magnetic hysteresis, and has put them at the forefront of high-performance single-molecule magnets (SMMs). Owing to the great success of design principles focused on maximising the anisotropy barrier, ever higher Ueff values have been reported leading to significant slow down of single-phonon Orbach spin relaxation. However, anisotropy-based SMM design has largely ignored two-phonon Raman spin relaxation, which is still limiting the temperatures at which a memory effect can be observed. In this work, we study the suppression of Raman relaxation through covalent bridging of the Cp ligands by alkyl chains, testing the hypothesis that increasing the rigidity of the ligand framework results in a blue shift of low frequency vibrations in the first coordination sphere of the Dy(III) ion. This reshaping of the vibrational low-energy density of states (DOS) results in lower occupation of pseudo-acoustic phonons available to drive Raman relaxation at low temperatures. We simulate Orbach and Raman spin relaxation in a series of zero-, mono-, di- and tri-bridged [Dy(Cpttt)2]+ analogues fully ab initio, using a quantum mechanics (QM)/molecular mechanics (MM) condensed phase embedding protocol in a periodic solvent matrix as a generic and experimentally testable environment model that can include (pseudo-)acoustic phononic degrees of freedom. We show that this approach can simulate magnetic relaxation dynamics in the condensed phase for the existing non-bridged [Dy(Cpttt)2]+ compound with quantitative experimental accuracy. Subsequently, we find a significant slowing down of Raman relaxation can be achieved for the singly-bridged SMM, while the introduction of further bridges leads to faster relaxation. A key result being that we find the two-phonon Raman rates correlate with the purity of the first-excited Kramers doublet in terms of its mJ = ±13/2 content. Even though the bridging design principle is successful at progressively reshaping the low-energy DOS, the introduction of linker atoms in the equatorial plane successively degrades magnetic anisotropy, suggesting the importance of refined design of the linker chemistry. The accuracy of our results emphasises the value of a generic periodic solvent embedding model, such that it permits the modelling of molecular spin dynamics in the condensed phase without knowledge of a crystal structure. This allows the study of hypothetical molecules or aggregates under real-world conditions, which we expect to have utility beyond the field of molecular magnetism.

Mathematical fundamentals of spherical kinematics of plate tectonics in terms of quaternions

To be a quantitative and testable tectonic model, plate tectonics requires spherical geometry and spherical kinematics in terms of finite rotations conveniently parametrized by their angle and axis and described by unit quaternions. In treatises on “Plate Tectonics” infinitesimal, instantaneous, and finite rotations, absolute and relative rotations are said to be applied to model the motion of tectonic plates. Even though these terms are strictly defined in mathematics, they are often casually used in geosciences. Here, their definitions are recalled and clarified as well as the terms rotation, orientation, and location on the sphere. For instance, infinitesimal rotations refer to a mathematical limit, when the angle of rotation tends to zero. Their rules do not apply to finite rotations, no matter how small their finite angles of rotation are. Mathematical approaches applying appropriate and feasible assumptions to model spherical motion of tectonic plates over geological times of hundreds of millions of years are derived including (i) sequences of incremental finite rotations, (ii) sequences of accumulating successive concatenations of finite rotations, and (iii) continuous rotations in terms of fully transient quaternions. The incremental and the accumulating approaches provide complementary views. While the relative Euler pole appears to migrate in the latter, it appears fixed in the former. Path, mean, and instantaneous velocity of the migrating Euler pole are derived as well as the angular and trajectoral velocity of the rotational motion about it. The approaches are illustrated by a geological example with actual data and a numerical yet geologically inspired example with artificial data. The former revisits the three‐plate scenario with stationary axes of two “absolute” rotations implying transient “relative” rotations about a migrating Euler pole and employs a proper plate‐circuit argument to determine them numerically without resorting to approximations. The latter applies an involved interplay of incremental and accumulating modeling inducing split–join cycles to approximate sinusoidal trajectories as reported to record plates' motion during the Gondwana breakup.