Microtubule buckling in an elastic matrix with quenched disorder

The intracellular elastic matrix has been recognized as an important factor to stabilize microtubules and increase their critical buckling force in vivo. This phenomenon was qualitatively explained by the Winkler model, which investigated buckling of a filament embedded in a homogeneous elastic medium. However, the assumption of homogeneity of the matrix in Winkler's, and other advanced models, is unrealistic inside cells, where the local environment is highly variable along the filament. Considering this to be a quenched-disorder system, we use a Poisson distribution for confinements, and apply the replica technique combined with the Gaussian variational method to address the buckling of a long filament. The results show two types of filament buckling: one corresponding to the first-order, and the other to a continuous second-order phase transition. The critical point, i.e. the switch from first- to second-order buckling transition, is induced by the increase in disorder strength. We also discover that this random disorder of the elastic environment destabilizes the filament by decreasing $P_c$ from the Winkler result, and the matrix with stronger mean elasticity has a stronger role of disorder (inhomogeneity). For microtubules in vivo, buckling follows the discontinuous first-order transition, with the threshold reduced to the fraction between 0.9 and 0.75 of the Winkler prediction for the homogeneous elastic matrix. We also show that disorder can affect the force-displacement relationship at non-zero temperature, while at zero temperature this effect vanishes.This work has been supported by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Mechanisms and rates of nucleation of amyloid fibrils

The classical nucleation theory finds the rate of nucleation proportional to the monomer concentration raised to the power, which is the `critical nucleaus size', n$_{c}$. The implicit assumption, that amyloids nucleate in the same way, has been recently challenged by an alternative two-step mechanism, when the soluble monomers first form a metastable aggregate (micelle), and then undergo conversion into the conformation rich in β-strands that are able to form a stable growing nucleus for the protofilament. Here we put together the elements of extensive knowledge about aggregation and nucleation kinetics, using a specific case of Aβ$_{1-42}$ amyloidogenic peptide for illustration, to find theoretical expressions for the effective rate of amyloid nucleation. We find that at low monomer concentration in solution, and also at low interaction energy between two peptide conformations in the micelle, the nucleation occurs via the classical route. At higher monomer concentration, and a range of other interaction parameters between peptides, the two-step `aggregation-conversion' mechanism of nucleation takes over. In this regime, the effective rate of the process can be interpreted as a power of monomer concentration in a certain range of parameters, however, the exponent is determined by a complicated interplay of interaction parameters and is not related to the minimum size of the growing nucleus (which we find to be $\sim$ 7-8 for Aβ$_{1-42}$).This work has been supported by the Theory of Condensed Matter Critical Mass Grant from EPSRC (EP/J017639)

Supporting Big Data Research at Case Western Reserve University

This report is an investigation of the research practices of faculty and research staff who utilize or support data science or big data methodologies at Case Western Reserve University (CWRU). The study was conducted by librarians and library staff within the Kelvin Smith Library (KSL) in collaboration with staff within CWRU University Technology ([U]tech), and was part of national selection of parallel studies occurring at public and private academic institutions throughout North America

Order effects of variability-contingent and variability-independent point delivery: Effects on operant variability and target sequence acquisition.

Previous research has shown that variability is a reinforceable dimension of operant behavior. Additionally, it has been demonstrated that learning is facilitated when variability in responding is high. In this research, variability was observed within an operant composed of any sequence of six left and right key presses. Variability was either a requirement for point delivery (VAR conditions) or points were delivered independent of variability (ANY conditions). Two groups of college undergraduates experienced different orders of conditions. One group began the experiment under VAR conditions, and the variability requirement was later removed. The other group began the experiment under ANY conditions, and the variability requirement was later added. A concurrently reinforced target sequence (i.e., an always-reinforced sequence of left and right key presses) was introduced to both groups after these orders of conditions had been experienced. A variety of outcomes resulted. Subjects learned the target sequence when variability was both high and low with non-target points concurrently available. Other subjects learned the target sequence after all non-target point deliveries had been suspended. One subject failed to acquire the target sequence at all. These results were compared to previous findings and possible explanations for the discrepancies were suggested

A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects

We thank the Genomic Technologies Facility (GTF) and the Central Imaging Facility (CIF) of the University of Lausanne for expert technical support. We thank Valérie Dénervaud Tendon, Guillaume Germion, Deborah Mühlemann, and Kayo Konishi for technical assistance and John Danku and Véronique Vacchina for ICP-MS analysis. This work was funded by grants from the Swiss National Science Foundation (SNSF), the European Research Council (ERC) to NG and a Human Frontiers Science Program (HFSP) grant to JT and NG. GL and CM were supported by the Agropolis foundation (Rhizopolis) and the Agence Nationale de la Recherche (HydroRoot; ANR-11-BSV6-018). MB was supported by a EMBO long-term postdoctoral fellowship, JEMV by a Marie Curie IEF fellowship and TK by the Japan Society for the Promotion of Sciences (JSPS).Peer reviewedPublisher PD

Breakdown and recovery in traffic flow models

Most car-following models show a transition from laminar to ``congested'' flow and vice versa. Deterministic models often have a density range where a disturbance needs a sufficiently large critical amplitude to move the flow from the laminar into the congested phase. In stochastic models, it may be assumed that the size of this amplitude gets translated into a waiting time, i.e.\ until fluctuations sufficiently add up to trigger the transition. A recently introduced model of traffic flow however does not show this behavior: in the density regime where the jam solution co-exists with the high-flow state, the intrinsic stochasticity of the model is not sufficient to cause a transition into the jammed regime, at least not within relevant time scales. In addition, models can be differentiated by the stability of the outflow interface. We demonstrate that this additional criterion is not related to the stability of the flow. The combination of these criteria makes it possible to characterize commonalities and differences between many existing models for traffic in a new way

Molecular Hydrodynamics: Vortex Formation and Sound Wave Propagation

In the present study, quantitative feasibility tests of the hydrodynamic description of a two-dimensional fluid at the molecular level are performed, both with respect to length and time scales. Using high-resolution fluid velocity data obtained from extensive molecular dynamics simulations, we computed the transverse and longitudinal components of the velocity field by the Helmholtz decomposition and compared them with those obtained from the linearized Navier-Stokes (LNS) equations with time-dependent transport coefficients. By investigating the vortex dynamics and the sound wave propagation in terms of these field components, we confirm the validity of the LNS description for times comparable to or larger than several mean collision times. The LNS description still reproduces the transverse velocity field accurately at smaller times, but it fails to predict characteristic patterns of molecular origin visible in the longitudinal velocity field. Based on these observations, we validate the main assumptions of the mode-coupling approach. The assumption that the velocity autocorrelation function can be expressed in terms of the fluid velocity field and the tagged particle distribution is found to be remarkably accurate even for times comparable to or smaller than the mean collision time. This suggests that the hydrodynamic-mode description remains valid down to the molecular scale

The effect of cigarette price increase on the cigarette consumption in Taiwan: evidence from the National Health Interview Surveys on cigarette consumption

BACKGROUND: This study uses cigarette price elasticity to evaluate the effect of a new excise tax increase on cigarette consumption and to investigate responses from various types of smokers. METHODS: Our sample consisted of current smokers between 17 and 69 years old interviewed during an annual face-to-face survey conducted by Taiwan National Health Research Institutes between 2000 to 2003. We used Ordinary Least Squares (OLS) procedure to estimate double logarithmic function of cigarette demand and cigarette price elasticity. RESULTS: In 2002, after Taiwan had enacted the new tax scheme, cigarette price elasticity in Taiwan was found to be -0.5274. The new tax scheme brought about an average annual 13.27 packs/person (10.5%) reduction in cigarette consumption. Using the cigarette price elasticity estimate from -0.309 in 2003, we calculated that if the Health and Welfare Tax were increased by another NT$ 3 per pack and cigarette producers shifted this increase to the consumers, cigarette consumption would be reduced by 2.47 packs/person (2.2%). The value of the estimated cigarette price elasticity is smaller than one, meaning that the tax will not only reduce cigarette consumption but it will also generate additional tax revenues. Male smokers who had no income or who smoked light cigarettes were found to be more responsive to changes in cigarette price. CONCLUSIONS: An additional tax added to the cost of cigarettes would bring about a reduction in cigarette consumption and increased tax revenues. It would also help reduce incidents smoking-related illnesses. The additional tax revenues generated by the tax increase could be used to offset the current financial deficiency of Taiwan's National Health Insurance program and provide better public services

Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.