Kinetic roughening in active interfaces

The essential features of many interfaces driven out of equilibrium are described by the same equation—the Kardar-Parisi-Zhang (KPZ) equation. How do living interfaces, such as the cell membrane, fit into this picture? In an endeavour to answer such a question, we proposed in [F. Cagnetta, M. R. Evans, D. Marenduzzo, PRL 120, 258001 (2018)] an idealised model for the membrane of a moving cell. Here we discuss how the addition of simple ingredients inspired by the dynamics of the membrane of moving cells affects common kinetic roughening theories such as the KPZ and Edwards-Wilkinson equations

Transient Overload Characteristics of PM-Assisted Synchronous Reluctance Machines, Including Sensorless Control Feasibility

Synchronous reluctance machines are a highefficiency alternative to induction motors for variable-speed applications. To mitigate the well-known downside of their lower power factor, permanent-magnet-assisted topologies, in which either rare-earth or ferrite magnets are inserted into the rotor in suitable quantities, are often adopted. The design and optimization procedures for PM-assisted topologies have been thoroughly discussed in the related literature. This paper compares synchronous reluctance machines assisted with NdFeB and ferrite magnets, focusing on torque overload capability and feasibility of saliency-based position estimation algorithms. Three prototypes were realized and tested. They all have the stator of a commercial induction motor and the same customdesigned synchronous reluctance rotor laminations. Of the three prototypes, one is a pure synchronous reluctance motor, and the other two have NdFeB and ferrite magnets, respectively; both are designed to give the same torque at rated current. Results from simulations and experiments are presented comparing the transient overload capability of the three machines, in terms of torque capability and de-magnetization limit. A dynamic thermal model of the machines was developed within this scope. Moreover, the feasibility of saliency-based sensorless methods was investigated and is presented here for the three machines, both at high- and low-current loads. The results of the paper suggest that the ferrite-assisted solution is the best candidate for replacing induction motors in variable-speed applications, for its optimal tradeoff between performance and cost

Analysis of overload and sensorless control capability of PM-assisted synchronous reluctance machines

Synchronous reluctance machines are a valid alternative to induction motors for industrial applications requiring variable speed regulation. To mitigate the well-known downside of their lower power factor, permanent-magnetassisted topologies are adopted. Both high-strength rare-earth magnets and low cost ferrite magnets can be used in such machines. Their design and optimization procedures have been discussed in related literature. This paper compares synchronous reluctance machines assisted with NdFeB and ferrite magnets, focusing on torque overload capability and feasibility of saliencybased position estimation algorithms. Three prototypes were realized and tested. They all have the stator of a commercial induction motor, and three custom synchronous reluctance rotors with same laminations: one has no magnets, the other two have NdFeB and ferrite magnets respectively, designed to give the same torque at rated current. Results from simulations and experiments are presented, focusing on torque and demagnetization limits in the over-current loading range. Moreover, the feasibility of saliency-based sensorless methods is investigated, both at high and low current loads. The results of the paper suggest that the ferrite-assisted solution is the candidate solution for replacing induction motors in variable speed applications

Statistical mechanics of a single active slider on a fluctuating interface

We study the statistical mechanics of a single active slider on a fluctuating interface, by means of numerical simulations and theoretical arguments. The slider, which moves by definition towards the interface minima, is active as it also stimulates growth of the interface. Even though such a particle has no counterpart in thermodynamic systems, active sliders may provide a simple model for ATP-dependent membrane proteins that activate cytoskeletal growth. We find a wide range of dynamical regimes according to the ratio between the timescales associated with the slider motion and the interface relaxation. If the interface dynamics is slow, the slider behaves like a random walker in a random envinronment which, furthermore, is able to escape environmental troughs by making them grow. This results in different dynamic exponens to the interface and the particle: the former behaves as an Edward-Wilkinson surface with dynamic exponent 2 whereas the latter has dynamic exponent 3/2. When the interface is fast, we get sustained ballistic motion with the particle surfing a membrane wave created by itself. However, if the interface relaxes immediately (i.e., it is infinitely fast), particle motion becomes symmetric and goes back to diffusive. Due to such a rich phenomenology, we propose the active slider as a toy model of fundamental interest in the field of active membranes and, generally, whenever the system constituent can alter the environment by spending energy.Comment: 13 pages, 19 figure

Inviscid limit of the active interface equations

We present a detailed solution of the active interface equations in the inviscid limit. The active interface equations were previously introduced as a toy model of membrane-protein systems: they describe a stochastic interface where growth is stimulated by inclusions which themselves move on the interface. In the inviscid limit, the equations reduce to a pair of coupled conservation laws. After discussing how the inviscid limit is obtained, we turn to the corresponding Riemann problem: the solution of the set of conservation laws with discontinuous initial condition. In particular, by considering two physically meaningful initial conditions, a giant trough and a giant peak in the interface, we elucidate the generation of shock waves and rarefaction fans in the system. Then, by combining several Riemann problems, we construct an oscillating solution of the active interface with periodic boundaries conditions. The existence of this oscillating state reflects the reciprocal coupling between the two conserved quantities in our system.Comment: 22 pages, 11 figure

RNA Docking and Local Translation Regulate Site-Specific Axon Remodeling In Vivo

Nascent proteins can be positioned rapidly at precise subcellular locations by local protein synthesis (LPS) to facilitate localized growth responses. Axon arbor architecture, a major determinant of synaptic connectivity, is shaped by localized growth responses, but it is unknown whether LPS influences these responses in vivo. Using high-resolution live imaging, we examined the spatiotemporal dynamics of RNA and LPS in retinal axons during arborization in vivo. Endogenous RNA tracking reveals that RNA granules dock at sites of branch emergence and invade stabilized branches. Live translation reporter analysis reveals that de novo ß-actin hotspots colocalize with docked RNA granules at the bases and tips of new branches. Inhibition of axonal ß-actin mRNA translation disrupts arbor dynamics primarily by reducing new branch emergence and leads to impoverished terminal arbors. The results demonstrate a requirement for LPS in building arbor complexity and suggest a key role for pre-synaptic LPS in assembling neural circuits.This work was supported by Cambridge Trust, Croucher Foundation, Sir Edward Youde Memorial Fund (H.H.-W.W.), Gates Cambridge (J.Q.L.), Fundac¸ a˜ o para a Cieˆ ncia e Tecnologia (C.M.R.), Wellcome Trust Senior Investigator Award (100329/Z/ 12/Z) (W.A.H.), EPSRC Grant (EP/H018301/1), MRC Grant (MR/K015850/1 and MR/K02292X/1), Wellcome Trust (089703/Z/09/Z) (C.F.K.), Wellcome Trust Programme Grant (085314/Z/08/Z), and ERC Advanced Grant (322817) (C.E.H.)

A simple cytofluorimetric score may optimize testing for biallelic CEBPA mutations in patients with acute myeloid leukemia

Acute myeloid leukemia with biallelic mutation of CEBPA (CEBPA-dm AML) is a distinct good prognosis entity recognized by WHO 2016 classification. However, testing for CEBPA mutation is challenging, due to the intrinsic characteristics of the mutation itself. Indeed, molecular analysis cannot be performed with NGS technique and requires Sanger sequencing. The association of recurrent mutations or translocations with specific immunophenotypic patterns has been already reported in other AML subtypes. The aim of this study was the development of a specific cytofluorimetric score (CEBPA-dm score), in order to distinguish patients who are unlikely to harbor the mutation. To this end, the correlation of CEBPA-dm score with the presence of the mutation was analyzed in 50 consecutive AML patients with normal karyotype and without NPM1 mutation (that is mutually exclusive with CEBPA mutation). One point each was assigned for expression of HLA DR, CD7, CD13, CD15, CD33, CD34 and one point for lack of expression of CD14. OS was not influenced by sex, age and CEBPA-dm score. Multivariate OS analysis showed that CEBPA-dm (p < 0.02) and FLT3-ITD (p < 0.01) were the strongest independent predictors of OS. With a high negative predictive value (100%), CEBPA-dm score < 6 was able to identify patients who are unlikely to have the mutation. Therefore, the application of this simple score might optimize the use of expensive and time-consuming diagnostic and prognostic assessment in the baseline work up of AML patients

Single Molecule Translation Imaging Visualizes the Dynamics of Local β-Actin Synthesis in Retinal Axons

Local mRNA translation occurs in growing axons enabling precise control of the proteome in response to signals. To measure quantitatively the spatiotemporal dynamics of protein synthesis in growth cones, we further developed a technique for single molecule translation imaging (SMTI). We report that Netrin-1 triggers a burst of β-actin synthesis at multiple non-repetitive sites, particularly in the periphery. The response is remarkably rapid starting within 20 seconds of cue application.This work was supported by grants from the Leverhulme Trust, the Engineering and Physical Sciences Research Council, UK (grant EP/H018301/1), the Medical Research Council (grant MR/K015850/1, and MR/K02292X/1), the Wellcome Trust (089703/Z/09/Z) (C.F.K.), Sir Edward Youde Memorial Fund, Croucher Foundation, Cambridge Trust (H.H.W.) Gates Cambridge Scholarship (J.Q.L.), Wellcome Trust Studentship (V.U.), European Research Council Advanced Grant (322817), the Wellcome Trust (085314/Z/08/Z) (C.E.H.)