Longitudinal Interactions Research Articles

On the coupling of the vertical, lateral and longitudinal wheel-rail interactions at high frequencies and the resulting irregular wear

A transient FE model of wheelset-rail rolling contact has been developed with ANSYS/Ls-dyna to simulate the high speed running of a free wheelset on a slab track. Applying vertical, lateral and longitudinal vibrations at the passing frequencies of typical short pitch corrugation to the wheelset with no initial lateral shift, it is found that the vertical and lateral wheel-rail interactions are coupled to a large extent, while the longitudinal relatively independent under rolling-sliding and dependent when approaching full-sliding. The resulting irregular wear calculated with implemented wear models of Archard, Tγ and Zobory increases in amplitude with the friction exploitation level, whereas its phase keeps rather stable under rolling-sliding. As full-sliding is approached, the phase shifts greatly in the presence of the vertical or lateral vibration, but not of the longitudinal vibration. Consequently, corrugation initiation from the vertical and lateral vibrations becomes harder if both full- and rolling-sliding wheels pass over.

A Description of Transverse Momentum Distributions in p+p Collisions at RHIC and LHC Energies

It has long been debated whether the hydrodynamics is suitable for the smaller colliding systems such as p+p collisions. In this paper, by assuming the existence of longitudinal collective motion and long-range interactions in the hot and dense matter created in p+p collisions, the relativistic hydrodynamics incorporating with the nonextensive statistics is used to analyze the transverse momentum distributions of the particles. The investigations of the present paper show that the hybrid model can give a good description of the currently available experimental data obtained in p+p collisions at RHIC and LHC energies, except for p and p¯ produced in the range of pT>3.0 GeV/c at s=200 GeV.

Inequality in Mobility: The Pursuit of Conjugal Intimacy for China’s Rural Migrant Women in Industrial Shenzhen

ABSTRACTExisting studies of dagongmei (China’s rural migrant woman workers) tend to situate them in the space of industrial production and, to a lesser extent, the site of everyday life. But we still do not know how their gender and mobility impact on their capacity to achieve personal intimacy; nor is it clear what social, economic and cultural forces may impede their search for it. This paper explores these questions by drawing on longitudinal ethnographic interactions with migrant women in Shenzhen who work for Foxconn – the world’s biggest multi-national electronics manufacturer. Focusing on the stories of three women, this discussion shifts the analysis of the body and labour from the public to the private sphere, thereby attempting to shed light on the link between intimacy, emotion and inequality in China’s capitalist industrial regime.

Readout of a weakly coupled qubit through the use of an auxiliary mode

The dispersive coupling between a qubit and a cavity mode is widely used for performing non-destructive readout of the qubit state. In this approach, it is typically required that the dispersive strong coupling regime is achieved. Here we show that the use of an auxiliary cavity mode reduces by orders of magnitude the required value of the dispersive coupling, for a given decay rate of the cavity mode. The analysis is performed within the input-output formalism, in terms of the photon scattering matrix elements and of the signal-to-noise ratio. We derive simple analytical expressions for the optimal parameters and recover the standard single-mode result as a limiting case. The present results can also be applied to the qubit readout based on longitudinal cavity-qubit interactions, and to any sensing scheme where the cavity frequency is used as a probe to estimate some physical parameter of interest.

A novel algorithm for longitudinal track-bridge interactions considering loading history and using a verified mechanical model of fasteners

The mechanical behavior of fasteners has considerable influence on track–bridge interaction (TBI) analysis, and a consensus has been gradually reached that their loading history and nonlinear characteristics should be taken into account. In this study, we present a new variation pattern of the longitudinal resistance of the fasteners considering loading history, which was experimentally verified based on the Dahl friction model. The model’s mechanical behavior was more consistent with measured results compared with previously proposed Ruge’s model and the double-spring model. According to the new model, an algorithm for TBI analysis considering loading history was derived based on the Ritz method and the principle of minimum potential energy, which was applied in a case study of an N-span, simply-supported girder bridge in a high-speed railway with a typical loading sequence: (1) the seasonal temperature change of the bridge; (2) the bending of the bridge structure under a vertical train load; (3) the braking of the train. Additionally, some significant conclusions were obtained by comparing the numerical results and adopting the mechanical parameters of the fasteners specified in various codes, according to both the linear superposition method (LSM) and loading history method (LHM).

TAPping into the treasures of tubulin using novel protein production methods.

Microtubules are cytoskeletal elements with important cellular functions, whose dynamic behaviour and properties are in part regulated by microtubule-associated proteins (MAPs). The building block of microtubules is tubulin, a heterodimer of α- and β-tubulin subunits. Longitudinal interactions between tubulin dimers facilitate a head-to-tail arrangement of dimers into protofilaments, while lateral interactions allow the formation of a hollow microtubule tube that mostly contains 13 protofilaments. Highly homologous α- and β-tubulin isotypes exist, which are encoded by multi-gene families. In vitro studies on microtubules and MAPs have largely relied on brain-derived tubulin preparations. However, these consist of an unknown mix of tubulin isotypes with undefined post-translational modifications. This has blocked studies on the functions of tubulin isotypes and the effects of tubulin mutations found in human neurological disorders. Fortunately, various methodologies to produce recombinant mammalian tubulins have become available in the last years, allowing researchers to overcome this barrier. In addition, affinity-based purification of tagged tubulins and identification of tubulin-associated proteins (TAPs) by mass spectrometry has revealed the ‘tubulome’ of mammalian cells. Future experiments with recombinant tubulins should allow a detailed description of how tubulin isotype influences basic microtubule behaviour, and how MAPs and TAPs impinge on tubulin isotypes and microtubule-based processes in different cell types.

Effect of Central Longitudinal Dipole Interactions on Chiral Liquid-Crystal Phases

Monte Carlo simulations of chiral liquid-crystals, represented by a simple coarse-grained chiral Gay–Berne model, were performed to investigate the effect of central longitudinal dipole interactions on phase behavior. A systematic analysis of the structural properties and phase behavior of both achiral and chiral systems, with dipole interactions, reveals differing effects; strong dipole interactions enhance the formation of layered structures; however, chiral interactions may prevent the formation of such phases under certain conditions. We also observed a short-ranged smectic structure within the cholesteric phases with strong dipole interactions. This constitutes possible evidence of presmectic ordering and/or the existence of chiral line liquid phases, which have previously been observed in X-ray experiments to occur between the smectic twisted grain boundary and cholesteric phases. These results provide a systematic understanding of how the phase behavior of chiral liquid-crystals changes when alterations are made to the strength of dipole interactions.

Flexural capacity model for RC beams strengthened with bolted side-plates incorporating both partial longitudinal and transverse interactions

Existing reinforced concrete (RC) beams with inadequate flexural capacity can be strengthened by bolting steel plates onto both sides of the face of beam. However, the effectiveness of these bolted side-plated (BSP) beams is affected by the mechanical slipping of bolts which is known as the partial interaction of the steel plates and the RC beam. To avoid overestimating the flexural capacity of the strengthened beam, the effects of partial interaction should be properly quantified in the structural design. Therefore, a new design model to determine the flexural capacity of BSP beams that takes into consideration both partial longitudinal and transverse interactions has been developed in this study. Strain and curvature factors are introduced to quantify the partial interaction. Based on these two factors, modified moment capacity equations are presented. The proposed model is then validated by comparing the analytical results with the test results from another study. Finally, a simplified design method is proposed based on the results of a parametric study.

Longitudinal Genotype-Phenotype Association Study through Temporal Structure Auto-Learning Predictive Model.

With the rapid development of high-throughput genotyping and neuroimaging techniques, imaging genetics has drawn significant attention in the study of complex brain diseases such as Alzheimer's disease (AD). Research on the associations between genotype and phenotype improves the understanding of the genetic basis and biological mechanisms of brain structure and function. AD is a progressive neurodegenerative disease; therefore, the study on the relationship between single nucleotide polymorphism (SNP) and longitudinal variations of neuroimaging phenotype is crucial. Although some machine learning models have recently been proposed to capture longitudinal patterns in genotype-phenotype association studies, most machine-learning models base the learning on fixed structure among longitudinal prediction tasks rather than automatically learning the interrelationships. In response to this challenge, we propose a new automated time structure learning model to automatically reveal the longitudinal genotype-phenotype interactions and exploits such learned structure to enhance the phenotypic predictions. We proposed an efficient optimization algorithm for our model and provided rigorous theoretical convergence proof. We performed experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort for longitudinal phenotype prediction, including 3123 SNPs and 2 biomarkers (Voxel-Based Morphometry and FreeSurfer). The empirical results validate that our proposed model is superior to the counterparts. In addition, the best SNPs identified by our model have been replicated in the literature, which justifies our prediction.

The Interaction of Genetic Predisposition and Socioeconomic Position With Type 2 Diabetes Mellitus: Cross-Sectional and Longitudinal Analyses From the Lifelines Cohort and Biobank Study.

A strong genetic predisposition for type 2 diabetes mellitus (T2DM) may aggravate the negative effects of low socioeconomic position (SEP) in the etiology of the disorder. This study aimed to examine cross-sectional and longitudinal associations and interactions of a genetic risk score (GRS) and SEP with T2DM and to investigate whether clinical and behavioral risk factors can explain these associations and interactions. We used data from 13,027 genotyped participants from the Lifelines study. The GRS was based on single-nucleotide polymorphisms genome-wide associated with T2DM and was categorized into tertiles. SEP was measured as educational level. T2DM was based on biological markers, recorded medication use, and self-reports. Cross-sectional and longitudinal associations and interactions between the GRS and SEP on T2DM were examined. The combination of a high GRS and low SEP had the strongest association with T2DM in cross-sectional (odds ratio = 3.84, 95% confidence interval = 2.28-6.46) and longitudinal analyses (hazard ratio = 2.71, 1.39-5.27), compared with a low GRS and high SEP. Interaction between a high GRS and a low SEP was observed in cross-sectional (relative excess risk due to interaction = 1.85, 0.65-3.05) but not in longitudinal analyses. Clinical and behavioral risk factors mostly explained the observed associations and interactions. A high GRS combined with a low SEP provides the highest risk for T2DM. These factors also exacerbated each other's impact cross-sectionally but not longitudinally. Preventive measures should target individual and contextual factors of this high-risk group to reduce the risk of T2DM.

On the exact solvability of the anisotropic central spin model: An operator approach

Using an operator approach based on a commutator scheme that has been previously applied to Richardson’s reduced BCS model and the inhomogeneous Dicke model, we obtain general exact solvability requirements for an anisotropic central spin model with XXZ-type hyperfine coupling between the central spin and the spin bath, without any prior knowledge of integrability of the model. We outline basic steps of the usage of the operators approach, and pedagogically summarize them into two Lemmas and two Constraints. Through a step-by-step construction of the eigen-problem, we show that the condition gj′2−gj2=c naturally arises for the model to be exactly solvable, where c is a constant independent of the bath-spin index j, and {gj} and {gj′} are the longitudinal and transverse hyperfine interactions, respectively. The obtained conditions and the resulting Bethe ansatz equations are consistent with that in previous literature.

Persistent influence of a narrative educational program on physician attitudes regarding patient care

Purpose: Educational approaches involving patient stories aim at enhancing empathy and patient-centered care; however, it is not known whether the influence of such programs on physician attitudes persists beyond medical school.Materials and methods: The Family Centered Experience (FCE) paired preclinical medical students with patient families over two years and engaged students in reflective dialogs about the volunteers’ stories. This study examined possible long-term influences on attitudes toward medicine and doctoring. Interviews were conducted with former students at the end of or after post-graduate training. All had completed the FCE between 4 and 10 years before the study. Thematic analysis was informed by a constructivist Grounded Theory approach.Results: Several themes were identified. The FCE made graduates aware of the patients’ perspectives and impacted their clinical practice in specific ways, such as developing collaborative partnerships, conducting family meetings, and breaking bad news. The course had influenced career choices and interest in teaching. Finally, the FCE enhanced appreciation of the human dimensions of medicine, which graduates had drawn upon in subsequent years.Conclusions: A program based on longitudinal interactions with individuals with chronic illness can have persistent influence by stimulating reflection on the patient’s perspective and humanistic approaches to patient care.

γ-Tubulin has a conserved intrinsic property of self-polymerization into double stranded filaments and fibrillar networks

γ-Tubulin is essential for microtubule nucleation and also plays less understood roles in nuclear and cell-cycle-related functions. High abundancy of γ-tubulin in acentrosomal Arabidopsis cells facilitated purification and biochemical characterization of large molecular species of γ-tubulin. TEM, fluorescence, and atomic force microscopy of purified high molecular γ-tubulin forms revealed the presence of linear filaments with a double protofilament substructure, filament bundles and aggregates. Filament formation from highly purified γ-tubulin free of γ-tubulin complex proteins (GCPs) was demonstrated for both plant and human γ-tubulin. Moreover, γ-tubulin associated with porcine brain microtubules formed oligomers. Experimental evidence on the intrinsic ability of γ-tubulin to oligomerize/polymerize was supported by conservation of α- and β-tubulin interfaces for longitudinal and lateral interactions for γ-tubulins. STED (stimulated emission depletion) microscopy of Arabidopsis cells revealed fine, short γ-tubulin fibrillar structures enriched on mitotic microtubular arrays that accumulated at polar regions of acentrosomal spindles and the outer nuclear envelope before mitosis, and were also present in nuclei. Fine fibrillar structures of γ-tubulin representing assemblies of higher order were localized in cell-cycle-dependent manner at sites of dispersed γ-tubulin location in acentrosomal plant cells as well as at sites of local γ-tubulin enrichment after drug treatment. Our findings that γ-tubulin preserves the capability of prokaryotic tubulins to self-organize into filaments assembling by lateral interaction into bundles/clusters help understanding of the relationship between structure and multiple cellular functions of this protein species and suggest that besides microtubule nucleation and organization, γ-tubulin may also have scaffolding or sequestration functions.

Mechanism of Microtubule Stabilization by Kinesin-5

In addition to their capacity to slide apart antiparallel microtubules during spindle formation, the mitotic kinesin-5 motor Eg5 has been shown to pause at microtubule plus-ends and enhance microtubule polymerization (Chen and Hancock, Nature Comm. 2015:8160). The goal of the present work is to understand the Eg5 microtubule polymerase mechanism by studying how the motor alters the lateral and longitudinal tubulin-tubulin interactions that stabilize the microtubule lattice. Transient kinetics and single-molecule tracking experiments demonstrate that dimeric Eg5 motors reside predominantly in a two-head-bound strong-binding state while stepping along the microtubule (Chen et al., JBC 2016:291(39), 20283-94). This suggests that when Eg5 pauses at a growing microtubule plus-end, the motor acts as a two-head-bound “staple” to stabilize the longitudinal bonds of incoming tubulin dimers. The on-rate for Eg5 binding to free tubulin is slow, suggesting that end-bound Eg5 motors do not bind free tubulin in solution; rather they stabilize incoming tubulin dimers that have bound to the plus-end. Because tubulin in the microtubule lattice resides in a “straight” conformation, while free tubulin resides in a “kinked” conformation, a second (non-mutually exclusive) model is that Eg5 stabilizes the straight conformation of tubulin. Consistent with this, monomeric Eg5 motors, which bind to the microtubule lattice without crosslinking tubulin dimers, also stabilize microtubules against depolymerization. Furthermore, the affinity of Eg5 for free tubulin is reduced in the presence of “wedge inhibitor” drugs that stabilize the kinked conformation of tubulin; conversely Eg5 binding to tubulin diminishes drug binding. Thus, we propose a microtubule polymerase mechanism in which binding by one Eg5 motor domain at the microtubule plus-end straightens tubulin dimers and stabilizes lateral tubulin-tubulin bonds, while the second Eg5 head binds incoming tubulin and acts as a staple to stabilize longitudinal tubulin-tubulin bonds and enhance microtubule growth.

Multi-hump bright solitons in a Schrödinger–mKdV system

We consider the problem of energy transport in a Davydov model along an anharmonic crystal medium obeying quartic longitudinal interactions corresponding to rigid interacting particles. The Zabusky and Kruskal unidirectional continuum limit of the original discrete equations reduces, in the long wave approximation, to a coupled system between the linear Schrödinger (LS) equation and the modified Korteweg–de Vries (mKdV) equation. Single- and two-hump bright soliton solutions for this LS–mKdV system are predicted to exist by variational means and numerically confirmed. The one-hump bright solitons are found to be the anharmonic supersonic analogue of the Davydov's solitons while the two-hump (in both components) bright solitons are found to be a novel type of soliton consisting of a two-soliton solution of mKdV trapped by the wave function associated to the LS equation. This two-hump soliton solution, as a two component solution, represents a new class of polaron solution to be contrasted with the two-soliton interaction phenomena from soliton theory, as revealed by a variational approach and direct numerical results for the two-soliton solution.

Modulation of lateral and longitudinal interdimeric interactions in microtubule models by Laulimalide and Peloruside A association: A molecular modeling approach on the mechanism of microtubule stabilizing agents.

Laulimalide (LAU) and Peloruside A (PLA) are non-taxane microtubule stabilizing agents with promising antimitotic properties. These ligands promote the assembly of microtubules (MTs) by targeting a unique binding site on β-tubulin. The X-ray structure for LAU/PLA-tubulin association was recently elucidated, but little information is available regarding the role of these ligands as modulators of interdimeric interactions across MTs. Herein, we report the use of molecular dynamics (MD), principal component analysis (PCA), MM/GBSA-binding free energy calculations, and computational alanine scanning mutagenesis (ASM) to examine effect of LAU/PLA association on lateral and longitudinal contacts between tubulin dimers in reduced MT models. MD and PCA results revealed that LAU/PLA exerts a strong restriction of lateral and longitudinal interdimeric motions, thus enabling the stabilization of the MT lattice. Besides structural effects, LAU/PLA induces a substantial strengthening of longitudinal interdimeric interactions, whereas lateral contacts are less affected by these ligands, as revealed by MM/GBSA and ASM calculations. These results are valuable to increase understanding about the molecular features involved in MT stabilization by LAU/PLA, and to design novel compounds capable of emulating the mode of action of these ligands.

A Longitudinal 1H-MRS Study of the Anterior Cingulate Gyrus in Child and Adolescent Victims of Multiple Forms of Violence

Background The anterior cingulate gyrus is involved in the extinction of conditioned fear responses and is implicated in the pathophysiology of posttraumatic stress disorder. The expression of N-acetylaspartate and choline may be altered in the anterior cingulate gyri of children and adolescents with posttraumatic stress disorder. Methods We conducted a proton magnetic resonance spectroscopy study, longitudinally investigating N-acetylaspartate/creatine and choline/creatine ratios in the anterior cingulate gyri of children and adolescents, aged from 8 to 12 years, who had been exposed to various forms of violence or were non-trauma control. Based on baseline posttraumatic stress symptoms (“sub-clinical”), participants were divided into two groups: posttraumatic stress (n = 19) and control (n = 19). Proton magnetic resonance spectroscopy scans were repeated a year later in trauma exposed participants. Trauma assessments included the Childhood Trauma Questionnaire. Results Exploratory analyses revealed a significant negative correlation between follow-up anterior cingulate gyrus N-acetylaspartate/creatine and Childhood Trauma Questionnaire scores in posttraumatic stress (r = −0.62, p = 0.01) but not control group (r = 0.16, p = 0.66). However, we found no significant differences in anterior cingulate gyrus N-acetylaspartate/creatine or choline/creatine between posttraumatic stress and control. In addition, there were no significant effects of time, group, or time-by-group interactions. Conclusions In this pediatric population, anterior cingulate gyrus N-acetylaspartate/creatine and choline/creatine were not affected by posttraumatic stress and on average these metabolites remained stable over time. However, the study provided intriguing preliminary evidence revealing that participants suffering from posttraumatic stress at baseline have shown, a year later, reduced anterior cingulate gyrus N-acetylaspartate/creatine among those with high trauma severity. This pilot evidence warrants replication in future studies to confirm these findings and to determine the longitudinal effects and interactions between childhood posttraumatic stress and trauma.

Phosphomimetic S3D cofilin binds but only weakly severs actin filaments

Many biological processes, including cell division, growth, and motility, rely on rapid remodeling of the actin cytoskeleton and on actin filament severing by the regulatory protein cofilin. Phosphorylation of vertebrate cofilin at Ser-3 regulates both actin binding and severing. Substitution of serine with aspartate at position 3 (S3D) is widely used to mimic cofilin phosphorylation in cells and in vitro The S3D substitution weakens cofilin binding to filaments, and it is presumed that subsequent reduction in cofilin occupancy inhibits filament severing, but this hypothesis has remained untested. Here, using time-resolved phosphorescence anisotropy, electron cryomicroscopy, and all-atom molecular dynamics simulations, we show that S3D cofilin indeed binds filaments with lower affinity, but also with a higher cooperativity than wild-type cofilin, and severs actin weakly across a broad range of occupancies. We found that three factors contribute to the severing deficiency of S3D cofilin. First, the high cooperativity of S3D cofilin generates fewer boundaries between bare and decorated actin segments where severing occurs preferentially. Second, S3D cofilin only weakly alters filament bending and twisting dynamics and therefore does not introduce the mechanical discontinuities required for efficient filament severing at boundaries. Third, Ser-3 modification (i.e. substitution with Asp or phosphorylation) "undocks" and repositions the cofilin N terminus away from the filament axis, which compromises S3D cofilin's ability to weaken longitudinal filament subunit interactions. Collectively, our results demonstrate that, in addition to inhibiting actin binding, Ser-3 modification favors formation of a cofilin-binding mode that is unable to sufficiently alter filament mechanical properties and promote severing.

Longitudinal interactions between brain and cognitive measures on reading development from 6 months to 14 years

Dyslexia is a neurobiological disorder impairing learning to read. Brain responses of infants at genetic risk for dyslexia are abnormal already at birth, and associations from infant speech perception to preschool cognitive skills and reading in early school years have been documented, but there are no studies showing predicting power until adolescence. Here we show that in at-risk infants, brain activation to pseudowords at left hemisphere predicts 44% of reading speed at 14 years, and even improves the prediction after taking into account neurocognitive preschool measures of letter naming, phonology, and verbal short-term memory. The association between infant brain responses and reading speed is mediated by preschool rapid automatized naming ability. Therefore, we suggest that rapid naming and reading speed could share a similar cognitive process of automatized access to lexicon via phonological representations, and brain activation to speech sounds in infancy probably acts as an index of deficient development of the same process.

Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules

Human histone deacetylase 6 (HDAC6) is the major deacetylase responsible for removing the acetyl group from Lys40 of α-tubulin (αK40), which is located lumenally in polymerized microtubules. Here, we provide a detailed kinetic analysis of tubulin deacetylation and HDAC6/microtubule interactions using individual purified components. Our data unequivocally show that free tubulin dimers represent the preferred HDAC6 substrate, with a KM value of 0.23 µM and a deacetylation rate over 1,500-fold higher than that of assembled microtubules. We attribute the lower deacetylation rate of microtubules to both longitudinal and lateral lattice interactions within tubulin polymers. Using TIRF microscopy, we directly visualized stochastic binding of HDAC6 to assembled microtubules without any detectable preferential binding to microtubule tips. Likewise, indirect immunofluorescence microscopy revealed that microtubule deacetylation by HDAC6 is carried out stochastically along the whole microtubule length, rather than from the open extremities. Our data thus complement prior studies on tubulin acetylation and further strengthen the rationale for the correlation between tubulin acetylation and microtubule age.