Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling

Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth.

Application of virtual certification techniques to vehicle design and track maintenance

Virtual certification partially substitutes by computer simulations the experimental techniques required for rail vehicle certification. In this paper, several works were these techniques were used in the vehicle design and track maintenance processes are presented. Dynamic simulation of multibody systems was used to virtually apply the EN14363 standard to certify the dynamic behaviour of vehicles. The works described are: assessment of a freight bogie design adapted to meter-gauge, assessment of a railway track layout for a subway network, freight bogie design with higher speed and axle load, and processing of the data acquired by a track recording vehicle for track maintenance.

The Dynamics of High-Speed Railway Bridges: A Review of Design Issues and New Research for Lateral Dynamics

The dynamic effects of high-speed trains on viaducts are important issues for the design of the structures, as well as for the consideration of safe running conditions for the trains. In this work we start by reviewing the relevance of some basic design aspects. The significance of impact factor envelopes for moving loads is considered first. Resonance which may be achieved for high-speed trains requires dynamic analysis, for which some key aspects are discussed. The relevance of performing a longitudinal distribution of axle loads, the number of modes taken in analysis, and the consideration of vehicle-structure interaction are discussed with representative examples. The lateral dynamic effects of running trains on bridges is of importance for laterally compliant viaducts, such as some very tall structures erected in new high-speed lines. The relevance of this study is mainly for the safety of the traffic, considering both internal actions such as the hunting motion as well as external actions such as wind or earthquakes [1]. These studies require three-dimensional dynamic coupled vehicle-bridge models, and consideration of wheel to rail contact, a phenomenon which is complex and costly to model in detail. We describe here a fully nonlinear coupled model, described in absolute coordinates and incorporated into a commercial finite element framework [2]. The wheel-rail contact has been considered using a FastSim algorithm which provides a compromise between accuracy and computational cost, and captures the main nonlinear response of the contact interface. Two applications are presented, firstly to a vehicle subject to a strong wind gust traversing a bridge, showing the relevance of the nonlinear wheel-rail contact model as well as the dynamic interaction between bridge and vehicle. The second application is to a real HS viaduct with a long continuous deck and tall piers and high lateral compliance [3]. The results show the safety of the traffic as well as the importance of considering features such as track alignment irregularities.

A molecular dynamics study of swift heavy ion irradiation of amorphous silica: the role of thermal effects

Irradiation with swift heavy ions (SHI), roughly defined as those having atomic masses larger than 15 and energies exceeding 1 MeV/amu, may lead to significant modification of the irradiated material in a nanometric region around the (straight) ion trajectory (latent tracks). In the case of amorphous silica, SHI irradiation originates nano-tracks of higher density than the virgin material (densification). As a result, the refractive index is increased with respect to that of the surroundings. Moreover, track overlapping leads to continuous amorphous layers that present a significant contrast with respect to the pristine substrate. We have recently demonstrated that SHI irradiation produces a large number of point defects, easily detectable by a number of experimental techniques (work presented in the parallel conference ICDIM). The mechanisms of energy transfer from SHI to the target material have their origin in the high electronic excitation induced in the solid. A number of phenomenological approaches have been employed to describe these mechanisms: coulomb explosion, thermal spike, non-radiative exciton decay, bond weakening. However, a detailed microscopic description is missing due to the difficulty of modeling the time evolution of the electronic excitation. In this work we have employed molecular dynamics (MD) calculations to determine whether the irradiation effects are related to the thermal phenomena described by MD (in the ps domain) or to electronic phenomena (sub-ps domain), e.g., exciton localization. We have carried out simulations of up to 100 ps with large boxes (30x30x8 nm3) using a home-modified version of MDCASK that allows us to define a central hot cylinder (ion track) from which heat flows to the surrounding cold bath (unirradiated sample). We observed that once the cylinder has cooled down, the Si and O coordination numbers are 4 and 2, respectively, as in virgin silica. On the other hand, the density of the (cold) cylinder increases with respect to that of silica and, furthermore, the silica network ring size decreases. Both effects are in agreement with the observed densification. In conclusion, purely thermal effects do not explain the generation of point defects upon irradiation, but they do account for the silica densification.

Assessment of the influence of the elastic properties of rail vehicle suspensions on safety, ride quality and track fatigue

A sensitivity analysis has been performed to assess the influence of the elastic properties of railway vehicle suspensions on the vehicle dynamic behaviour. To do this, 144 dynamic simulations were performed modifying, one at a time, the stiffness and damping coefficients, of the primary and secondary suspensions. Three values were assigned to each parameter, corresponding to the percentiles 10, 50 and 90 of a data set stored in a database of railway vehicles.After processing the results of these simulations, the analyzed parameters were sorted by increasing influence. It was also found which of these parameters could be estimated with a lesser degree of accuracy in future simulations without appreciably affecting the simulation results. In general terms, it was concluded that the highest influences were found for the longitudinal stiffness and the lateral stiffness of the primary suspension, and the lowest influences for the vertical stiffness and the vertical damping of the primary suspension, with the parameters of the secondary suspension showing intermediate influences between them.

Nonlinear models for lateral dynamics of railway vehicles on bridges subject to wind action

The study of lateral dynamics of running trains on bridges is of importance mainly for the safety of the traffic, and may be relevant for laterally compliant bridges. These studies require threedimensional coupled vehicle-bridge models, wheree consideration of wheel to rail contact is a key aspect. Furthermore, an adequate evaluation of safety of rail traffic requires nonlinear models. A nonlinear coupled model is proposed here for vehicle-structure vertical and lateral dynamics. Vehicles are considered as fully three-dimensional multibody systems including gyroscopic terms and large rotation effects. The bridge structure is modeled by means of finite elements which may be of beam, shell or continuum type and may include geometric or material nonlinearities. The track geometry includes distributed track alignment irregularities. Both subsystems (bridge and vehicles) are described with coordinates in absolute reference frames, as opposed to alternative approaches which describe the multibody system with coordinates relative to the base bridge motion. The wheelrail contact employed is a semi-Hertzian model based on realistic wheel-rail profiles. It allows a detailed geometrical description of the contact patch under each wheel including multiple-point contact, flange contact and uplift. Normal and tangential stresses in each contact are integrated at each time-step to obtain the resultant contact forces. The models have been implemented within an existing finite element analysis software with multibody capabilities, Abaqus (Simulia Ltd., 2010). Further details of the model are presented in Antolín et al. (2012). Representative applications are presented for railway vehicles under lateral wind action on laterally compliant viaducts, showing the relevance of the nonlinear wheel-rail contact model as well as the interaction between bridge and vehicle.

Advanced motorcycle handling and dynamics. Summary technical report - volume I. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Advanced motorcycle handling and dynamics. Appendix A - volume III. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Advanced motorcycle handling and dynamics. Final technical report - volume II. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Objective accommodative amplitude and dynamics with the 1CU accommodative intraocular lens

PURPOSE. To compare the objective accommodative amplitude and dynamics of eyes implanted with the one-compartment-unit (1CU; HumanOptics AG, Erlangen, Germany) accommodative intraocular lenses (IOLs) with that measured subjectively. METHODS. Twenty eyes with a 1CU accommodative IOL implanted were refracted and distance and near acuity measured with a logMAR (logarithm of the minimum angle of resolution) chart. The objective accommodative stimulus-response curve for static targets between 0.17 and 4.00 D accommodative demand was measured with the SRW-5000 (Shin-Nippon Commerce Inc., Tokyo, Japan) and PowerRefractor (PlusOptiX, Nürnberg, Germany) autorefractors. Continuous objective recording of dynamic accommodation was measured with the SRW-5000, with the subject viewing a target moving from 0 to 2.50 D at 0.3 Hz through a Badal lens system. Wavefront aberrometry measures (Zywave; Bausch & Lomb, Rochester, NY) were made through undilated pupils. Subjective amplitude of accommodation was measured with the RAF (Royal Air Force accommodation and vergence measurement) rule. RESULTS. Four months after implantation best-corrected acuity was -0.01 ± 0.16 logMAR at distance and 0.60 ± 0.09 logMAR at near. Objectively, the static amplitude of accommodation was 0.72 ± 0.38 D. The average dynamic amplitude of accommodation was 0.71 ± 0.47 D, with a lag behind the target of 0.50 ± 0.48 seconds. Aberrometry showed a decrease in power of the lens-eye combination from the center to the periphery in all subjects (on average, -0.38 ± 0.28 D/mm). Subjective amplitude of accommodation was 2.24 ± 0.42 D. Two years after 1CU implantation, refractive error and distance visual acuity remained relatively stable, but near visual acuity, and the subjective and objective amplitudes of accommodation decreased. CONCLUSIONS. The objective accommodating effects of the 1CU lens appear to be limited, although patients are able to track a moving target. Subjective and objective accommodation was reduced at the 2-year follow-up. The greater subjective amplitude of accommodation is likely to result from the eye's depth of focus of and the aspheric nature of the IOL. Copyright © Association for Research in Vision and Ophthalmology.

Mechanical Properties And Fracture Dynamics Of Silicene Membranes.

As graphene has become one of the most important materials, there is renewed interest in other similar structures. One example is silicene, the silicon analogue of graphene. It shares some of the remarkable graphene properties, such as the Dirac cone, but presents some distinct ones, such as a pronounced structural buckling. We have investigated, through density functional based tight-binding (DFTB), as well as reactive molecular dynamics (using ReaxFF), the mechanical properties of suspended single-layer silicene. We calculated the elastic constants, analyzed the fracture patterns and edge reconstructions. We also addressed the stress distributions, unbuckling mechanisms and the fracture dependence on the temperature. We analysed the differences due to distinct edge morphologies, namely zigzag and armchair.

Site Specific Spin Dynamics In Bafe2as2: Tuning The Ground State By Orbital Differentiation.

The role of orbital differentiation on the emergence of superconductivity in the Fe-based superconductors remains an open question to the scientific community. In this investigation, we employ a suitable microscopic spin probe technique, namely Electron Spin Resonance (ESR), to investigate this issue on selected chemically substituted BaFe2As2 single crystals. As the spin-density wave (SDW) phase is suppressed, we observe a clear increase of the Fe 3d bands anisotropy along with their localization at the FeAs plane. Such an increase of the planar orbital content is interestingly independent of the chemical substitution responsible for suppressing the SDW phase. As a consequence, the magnetic fluctuations in combination with this particular symmetry of the Fe 3d bands are propitious ingredients for the emergence of superconductivity in this class of materials.

[between The Country And The Laboratory: The Dynamics Of The Production Of Knowledge At The Menopause Outpatients Clinic At Caism, Unicamp.]

This study investigates the practices involved in the production of knowledge about menopause at Caism, Unicamp, a reference center for public policies for women's health. Gynecological appointments and psychological support meetings were observed, and women and doctors were interviewed in order to identify what discourse circulates there and how different actors are brought in to ensure that the knowledge produced attains credibility and travels beyond the boundaries of the teaching hospital to become universal. The analysis is based on localized studies aligned with social studies of science and technology.

On The Consistency Of Monte Carlo Track Structure Dna Damage Simulations.

Monte Carlo track structures (MCTS) simulations have been recognized as useful tools for radiobiological modeling. However, the authors noticed several issues regarding the consistency of reported data. Therefore, in this work, they analyze the impact of various user defined parameters on simulated direct DNA damage yields. In addition, they draw attention to discrepancies in published literature in DNA strand break (SB) yields and selected methodologies. The MCTS code Geant4-DNA was used to compare radial dose profiles in a nanometer-scale region of interest (ROI) for photon sources of varying sizes and energies. Then, electron tracks of 0.28 keV-220 keV were superimposed on a geometric DNA model composed of 2.7 × 10(6) nucleosomes, and SBs were simulated according to four definitions based on energy deposits or energy transfers in DNA strand targets compared to a threshold energy ETH. The SB frequencies and complexities in nucleosomes as a function of incident electron energies were obtained. SBs were classified into higher order clusters such as single and double strand breaks (SSBs and DSBs) based on inter-SB distances and on the number of affected strands. Comparisons of different nonuniform dose distributions lacking charged particle equilibrium may lead to erroneous conclusions regarding the effect of energy on relative biological effectiveness. The energy transfer-based SB definitions give similar SB yields as the one based on energy deposit when ETH ≈ 10.79 eV, but deviate significantly for higher ETH values. Between 30 and 40 nucleosomes/Gy show at least one SB in the ROI. The number of nucleosomes that present a complex damage pattern of more than 2 SBs and the degree of complexity of the damage in these nucleosomes diminish as the incident electron energy increases. DNA damage classification into SSB and DSB is highly dependent on the definitions of these higher order structures and their implementations. The authors' show that, for the four studied models, different yields are expected by up to 54% for SSBs and by up to 32% for DSBs, as a function of the incident electrons energy and of the models being compared. MCTS simulations allow to compare direct DNA damage types and complexities induced by ionizing radiation. However, simulation results depend to a large degree on user-defined parameters, definitions, and algorithms such as: DNA model, dose distribution, SB definition, and the DNA damage clustering algorithm. These interdependencies should be well controlled during the simulations and explicitly reported when comparing results to experiments or calculations.