Inhibition of protein synthesis leading to unfolded protein response is the major event in abrin-mediated apoptosis

Abrin obtained from the plant Abrus precatorius inhibits protein synthesis and also triggers apoptosis in cells. Previous studies from our laboratory suggested a link between these two events. Using an active site mutant of abrin A-chain which exhibits 225-fold lower protein synthesis inhibitory activity than the wild-type abrin A-chain, we demonstrate in this study that inhibition of protein synthesis induced by abrin is the major factor triggering unfolded protein response leading to apoptosis. Since abrin A-chain requires the B-chain for internalization into cells, the wild-type and mutant recombinant abrin A-chains were conjugated to native ricin B-chain to generate hybrid toxins, and the toxic effects of the two conjugates were compared. The rate of inhibition of protein synthesis mediated by the mutant ricin B-rABRA (R167L) conjugate was slower than that of the wild-type ricin B-rABRA conjugate as expected. The mutant conjugate activated p38MAPK and caspase-3 similar to its wild-type counterpart although at later time points. Overall, these results confirm that inhibition of protein synthesis is the major event contributing to abrin-mediated apoptosis.

A hybrid method for stochastic response analysis of a vibrating structure

Response analysis of a linear structure with uncertainties in both structural parameters and external excitation is considered here. When such an analysis is carried out using the spectral stochastic finite element method (SSFEM), often the computational cost tends to be prohibitive due to the rapid growth of the number of spectral bases with the number of random variables and the order of expansion. For instance, if the excitation contains a random frequency, or if it is a general random process, then a good approximation of these excitations using polynomial chaos expansion (PCE) involves a large number of terms, which leads to very high cost. To address this issue of high computational cost, a hybrid method is proposed in this work. In this method, first the random eigenvalue problem is solved using the weak formulation of SSFEM, which involves solving a system of deterministic nonlinear algebraic equations to estimate the PCE coefficients of the random eigenvalues and eigenvectors. Then the response is estimated using a Monte Carlo (MC) simulation, where the modal bases are sampled from the PCE of the random eigenvectors estimated in the previous step, followed by a numerical time integration. It is observed through numerical studies that this proposed method successfully reduces the computational burden compared with either a pure SSFEM of a pure MC simulation and more accurate than a perturbation method. The computational gain improves as the problem size in terms of degrees of freedom grows. It also improves as the timespan of interest reduces.

Response Dynamics of Recirculation Structures in Coaxial Nonpremixed Swirl-Stabilized Flames Subjected to Acoustic Forcing

This paper reports the time-mean and phase-locked response of nonreacting as well as reacting flow field in a coaxial swirling jet/flame (nonpremixed). Two distinct swirl intensities plus two different central pipe flow rates at each swirl setting are investigated. The maximum response is observed at the 105 Hz mode in the range of excitation frequencies (0-315 Hz). The flow/flame exhibited minimal response beyond 300 Hz. It is seen that the aspect ratio change of inner recirculation zone (IRZ) under nonreacting conditions (at responsive modes) manifests as a corresponding increase in the time-mean flame aspect ratio. This is corroborated by similar to 25% decrease in the IRZ transverse width in both flame and cold flow states. In addition, 105 Hz excited states are found to shed high energy regions (eddies) asymmetrically when compared to dormant 315 Hz pulsing frequency. The kinetic energy (KE) of the flow field is subsequently reduced due to acoustic excitation and a corresponding increase (similar to O (1)) in fluctuation intensity is witnessed. The lower swirl intensity case is found to be more responsive than the high swirl case as in the former flow state the resistance offered by IRZ to incoming acoustic perturbations is lower due to inherently low inertia. Next, the phase-locked analysis of flow and flame structure is employed to further investigate the phase dependence of flow/flame response. It is found that the asymmetric shifting of IRZ mainly results at 270 deg acoustic forcing. The 90 deg phase angle forcing is observed to convect the IRZ farther downstream in both swirl cases as compared to other phase angles. The present work aims primarily at providing a fluid dynamic view point to the observed nonpremixed flame response without considering the confinement effects.

Simulated long-term climate response to idealized solar geoengineering

Solar geoengineering has been proposed as a potential means to counteract anthropogenic climate change, yet it is unknown how such climate intervention might affect the Earth's climate on the millennial time scale. Here we use the HadCM3L model to conduct a 1000year sunshade geoengineering simulation in which solar irradiance is uniformly reduced by 4% to approximately offset global mean warming from an abrupt quadrupling of atmospheric CO2. During the 1000year period, modeled global climate, including temperature, hydrological cycle, and ocean circulation of the high-CO2 simulation departs substantially from that of the control preindustrial simulation, whereas the climate of the geoengineering simulation remains much closer to that of the preindustrial state with little drift. The results of our study do not support the hypothesis that nonlinearities in the climate system would cause substantial drift in the climate system if solar geoengineering was to be deployed on the timescale of a millennium.

Modelling and analysis of an open-loop induction motor drive incorporating the effect of inverter dead-time

The objective of this paper is to study the influence of inverter dead-time on steady as well as dynamic operation of an open-loop induction motor drive fed from a voltage source inverter (VSI). Towards this goal, this paper presents a systematic derivation of a dynamic model for an inverter-fed induction motor, incorporating the effect of inverter dead-time, in the synchronously revolving dq reference frame. Simulation results based on this dynamic model bring out the impact of inverter dead-time on both the transient response and steady-state operation of the motor drive. For the purpose of steady-state analysis, the dynamic model of the motor drive is used to derive a steady-state model, which is found to be non-linear. The steady-state model shows that the impact of dead-time can be seen as an additional resistance in the stator circuit, whose value depends on the stator current. Towards precise evaluation of this dead-time equivalent resistance, an analytical expression is proposed for the same in terms of inverter dead-time, switching frequency, modulation index and load impedance. The notion of dead-time equivalent resistance is shown to simplify the solution of the non-linear steady-state model. The analytically evaluated steady-state solutions are validated through numerical simulations and experiments.

Identification of nonlinear dynamic systems: Time-frequency filtering and skeleton curves

The nonlinear behavior varying with the instantaneous response was analyzed through the joint time-frequency analysis method for a class of S. D. O. F nonlinear system. A masking operator an definite regions is defined and two theorems are presented. Based on these, the nonlinear system is modeled with a special time-varying linear one, called the generalized skeleton linear system (GSLS). The frequency skeleton curve and the damping skeleton curve are defined to describe the main feature of the non-linearity as well. Moreover, an identification method is proposed through the skeleton curves and the time-frequency filtering technique.

Increasing Critical Sensitivity of the Load/Unload Response Ratio before Large Earthquakes with Identified Stress Acclumulation Pattern

The Load/Unload Response Ratio (LURR) method is proposed for short-to-intermediate-term earthquake prediction [Yin, X.C., Chen, X.Z., Song, Z.P., Yin, C., 1995. A New Approach to Earthquake Prediction — The Load/Unload Response Ratio (LURR) Theory, Pure Appl. Geophys., 145, 701–715]. This method is based on measuring the ratio between Benioff strains released during the time periods of loading and unloading, corresponding to the Coulomb Failure Stress change induced by Earth tides on optimally oriented faults. According to the method, the LURR time series usually climb to an anomalously high peak prior to occurrence of a large earthquake. Previous studies have indicated that the size of critical seismogenic region selected for LURR measurements has great influence on the evaluation of LURR. In this study, we replace the circular region usually adopted in LURR practice with an area within which the tectonic stress change would mostly affect the Coulomb stress on a potential seismogenic fault of a future event. The Coulomb stress change before a hypothetical earthquake is calculated based on a simple back-slip dislocation model of the event. This new algorithm, by combining the LURR method with our choice of identified area with increased Coulomb stress, is devised to improve the sensitivity of LURR to measure criticality of stress accumulation before a large earthquake. Retrospective tests of this algorithm on four large earthquakes occurred in California over the last two decades show remarkable enhancement of the LURR precursory anomalies. For some strong events of lesser magnitudes occurred in the same neighborhoods and during the same time periods, significant anomalies are found if circular areas are used, and are not found if increased Coulomb stress areas are used for LURR data selection. The unique feature of this algorithm may provide stronger constraints on forecasts of the size and location of future large events.

Identification of Nonlinear Systems Through Time-Frequency Filtering Technique

In the previous paper, a class of nonlinear system is mapped to a so-called skeleton linear model (SLM) based on the joint time-frequency analysis method. Behavior of the nonlinear system may be indicated quantitatively by the variance of the coefficients of SLM versus its response. Using this model we propose an identification method for nonlinear systems based on nonstationary vibration data in this paper. The key technique in the identification procedure is a time-frequency filtering method by which solution of the SLM is extracted from the response data of the corresponding nonlinear system. Two time-frequency filtering methods are discussed here. One is based on the quadratic time-frequency distribution and its inverse transform, the other is based on the quadratic time-frequency distribution and the wavelet transform. Both numerical examples and an experimental application are given to illustrate the validity of the technique.

Load-Unload Response Ratio and Accelerating Moment/Energy Release Critical Region Scaling and Earthquake Prediction

The main idea of the Load-Unload Response Ratio (LURR) is that when a system is stable, its response to loading corresponds to its response to unloading, whereas when the system is approaching an unstable state, the response to loading and unloading becomes quite different. High LURR values and observations of Accelerating Moment/Energy Release (AMR/AER) prior to large earthquakes have led different research groups to suggest intermediate-term earthquake prediction is possible and imply that the LURR and AMR/AER observations may have a similar physical origin. To study this possibility, we conducted a retrospective examination of several Australian and Chinese earthquakes with magnitudes ranging from 5.0 to 7.9, including Australia's deadly Newcastle earthquake and the devastating Tangshan earthquake. Both LURR values and best-fit power-law time-to-failure functions were computed using data within a range of distances from the epicenter. Like the best-fit power-law fits in AMR/AER, the LURR value was optimal using data within a certain epicentral distance implying a critical region for LURR. Furthermore, LURR critical region size scales with mainshock magnitude and is similar to the AMR/AER critical region size. These results suggest a common physical origin for both the AMR/AER and LURR observations. Further research may provide clues that yield an understanding of this mechanism and help lead to a solid foundation for intermediate-term earthquake prediction.

An evaluation of space time cube representation of spatiotemporal patterns.

Space time cube representation is an information visualization technique where spatiotemporal data points are mapped into a cube. Information visualization researchers have previously argued that space time cube representation is beneficial in revealing complex spatiotemporal patterns in a data set to users. The argument is based on the fact that both time and spatial information are displayed simultaneously to users, an effect difficult to achieve in other representations. However, to our knowledge the actual usefulness of space time cube representation in conveying complex spatiotemporal patterns to users has not been empirically validated. To fill this gap, we report on a between-subjects experiment comparing novice users' error rates and response times when answering a set of questions using either space time cube or a baseline 2D representation. For some simple questions, the error rates were lower when using the baseline representation. For complex questions where the participants needed an overall understanding of the spatiotemporal structure of the data set, the space time cube representation resulted in on average twice as fast response times with no difference in error rates compared to the baseline. These results provide an empirical foundation for the hypothesis that space time cube representation benefits users analyzing complex spatiotemporal patterns.

The Trade-offs with Space Time Cube Representation of Spatiotemporal Patterns

Space time cube representation is an information visualization technique where spatiotemporal data points are mapped into a cube. Fast and correct analysis of such information is important in for instance geospatial and social visualization applications. Information visualization researchers have previously argued that space time cube representation is beneficial in revealing complex spatiotemporal patterns in a dataset to users. The argument is based on the fact that both time and spatial information are displayed simultaneously to users, an effect difficult to achieve in other representations. However, to our knowledge the actual usefulness of space time cube representation in conveying complex spatiotemporal patterns to users has not been empirically validated. To fill this gap we report on a between-subjects experiment comparing novice users error rates and response times when answering a set of questions using either space time cube or a baseline 2D representation. For some simple questions the error rates were lower when using the baseline representation. For complex questions where the participants needed an overall understanding of the spatiotemporal structure of the dataset, the space time cube representation resulted in on average twice as fast response times with no difference in error rates compared to the baseline. These results provide an empirical foundation for the hypothesis that space time cube representation benefits users when analyzing complex spatiotemporal patterns.

Time-Frequency Analysis of Nonlinear Systems: The Skeleton Linear Model and the Skeleton Curves

The joint time-frequency analysis method is adopted to study the nonlinear behavior varying with the instantaneous response for a class of S.D.O.F nonlinear system. A time-frequency masking operator, together with the conception of effective time-frequency region of the asymptotic signal are defined here. Based on these mathematical foundations, a so-called skeleton linear model (SLM) is constructed which has similar nonlinear characteristics with the nonlinear system. Two skeleton curves are deduced which can indicate the stiffness and damping in the nonlinear system. The relationship between the SLM and the nonlinear system, both parameters and solutions, is clarified. Based on this work a new identification technique of nonlinear systems using the nonstationary vibration data will be proposed through time-frequency filtering technique and wavelet transform in the following paper.

Short-Term Nonlinear Response of Tension Leg Platform in Random Sea Waves

Most of the existing mathematical models for analyzing the dynamic response of TLP are based on explicit or implicit assumptions that motions (translations and rotations) are small magnitude. However, when TLP works in severe adverse conditions, the a priori assumption on small displacements may be inadequate. In such situation, the motions should be regarded as finite magnitude. This paper will study stochastic nonlinear dynamic responses of TLP with finite displacements in random waves. The nonlinearities considered are: large amplitude motions, coupling the six degrees-of-freedom, instantaneous position, instantaneous wet surface, free surface effects and viscous drag force. The nonlinear dynamic responses are calculated by using numerical integration procedure in the time domain. After the time histories of the dynamic responses are obtained, we carry out cycle counting of the stress histories of the tethers with rain-flow counting method to get the stress range distribution.

Streamflow response of a small forested catchment on different timescales

The hydrological response of a catchment to rainfall on different timescales is result of a complex system involving a range of physical processes which may operate simultaneously and have different spatial and temporal influences. This paper presents the analysis of streamflow response of a small humid-temperate catchment (Aixola, 4.8 km(2)) in the Basque Country on different timescales and discusses the role of the controlling factors. Firstly, daily time series analysis was used to establish a hypothesis on the general functioning of the catchment through the relationship between precipitation and discharge on an annual and multiannual scale (2003-2008). Second, rainfall-runoff relationships and relationships among several hydrological variables, including catchment antecedent conditions, were explored at the event scale (222 events) to check and improve the hypothesis. Finally, the evolution of electrical conductivity (EC) during some of the monitored storm events (28 events) was examined to identify the time origin of waters. Quick response of the catchment to almost all the rainfall events as well as a considerable regulation capacity was deduced from the correlation and spectral analyses. These results agree with runoff event scale data analysis; however, the event analysis revealed the non-linearity of the system, as antecedent conditions play a significant role in this catchment. Further, analysis at the event scale made possible to clarify factors controlling (precipitation, precipitation intensity and initial discharge) the different aspects of the runoff response (runoff coefficient and discharge increase) for this catchment. Finally, the evolution of EC of the waters enabled the time origin (event or pre-event waters) of the quickflow to be established; specifically, the conductivity showed that pre-event waters usually represent a high percentage of the total discharge during runoff peaks. The importance of soil waters in the catchment is being studied more deeply.

Random response of nonlinear continuous systems

This thesis presents a technique for obtaining the stochastic response of a nonlinear continuous system. First, the general method of nonstationary continuous equivalent linearization is developed. This technique allows replacement of the original nonlinear system with a time-varying linear continuous system. Next, a numerical implementation is described which allows solution of complex problems on a digital computer. In this procedure, the linear replacement system is discretized by the finite element method. Application of this method to systems satisfying the one-dimensional wave equation with two different types of constitutive nonlinearities is described. Results are discussed for nonlinear stress-strain laws of both hardening and softening types.