Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates.

Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC-CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.

Cell cycle start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates

© 2016 Burnetti et al. Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC-CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.

Predicting optimal process conditions for flip-chip aassembly using copper column bumped dies

Recently, research has been carried out to test a novel bumping method which omits the under bump metallurgy (UBM) forming process by bonding copper columns directly onto the Al pads of the silicon dies. This bumping method could be adopted to simplify the flip chip assembly process, increase the productivity and achieve a higher I/O count. Computer modelling methods are used to predict the shape of solder joints and response of the flip chip to thermal cyclic loading. The accumulated plastic strain energy at the comer solder joints is used as the damage indicator. Models with a range of design parameters have been compared for their reliability. The ranking of the relative importance of these parameters is given. Results from these analyses are being used by our industrial and academic partners to identify optimal design conditions.

Computer modelling of the reliability of flip chips with metal column bumping

Recently, research has been carried out to test a novel bumping method which omits the under bump metallurgy forming process by bonding copper columns directly onto the Al pads of the silicon dies. This bumping method could be adopted to simplify the flip chip manufacturing process, increase the productivity and achieve a higher I/O count. This paper describes an investigation of the solder joint reliability of flip-chips based on this new bumping process. Computer modelling methods are used to predict the shape of solder joints and response of flip chips to thermal cyclic loading. The accumulated plastic strain energy at the comer solder joints is used as the damage indicator. Models with a range of design parameters have been compared for their reliability. The parameters that have been investigated are the copper column height, radius and solder volume. The ranking of the relative importance of these parameters is given. For most of the results presented in the paper, the solder material has been assumed to be the lead-free 96.5Sn3.5Ag alloy but some results for 60Sn40Pb solder joints have also been presented.

The effect of thermal cycle profiles on solder joint damage

The relationship between the damage caused at different thermal cycles is very important. The whole of accelerated thermal cycle testing is based on the premise that damage at one cycle is representative of damage at a different cycle. In this paper, the relative damage caused by six thermal cycle profiles are predicted using Finite Element (FE) modelling and the results validated against experiments. Both creep strain and strain energy density were used as damage indicators and creep strain was found to correlate better with experiment. The validated FE model is then used to investigate the effect of altering each of the thermal profile parameters (ramp and swell times, hot and cold temperatures). The components used for testing are surface mount resistors - 1206, 0805 and 0603. The solders investigated are eutectic SnAgCu and eutectic SnAg.

Identifying the damage mechanisms in paper using the acoustic emission monitoring technique

This paper investigates the use of the acoustic emission (AE) monitoring technique for use in identifying the damage mechanisms present in paper associated with its production process. The microscopic structure of paper consists of a random mesh of paper fibres connected by hydrogen bonds. This implies the existence of two damage mechanisms, the failure of a fibre-fibre bond and the failure of a fibre. This paper describes a hybrid mathematical model which couples the mechanics of the mass-spring model to the acoustic wave propagation model for use in generating the acoustic signal emitted by complex structures of paper fibres under strain. The derivation of the mass-spring model can be found in [1,2], with details of the acoustic wave equation found in [3,4]. The numerical implementation of the vibro-acoustic model is discussed in detail with particular emphasis on the damping present in the numerical model. The hybrid model uses an implicit solver which intrinsically introduces artificial damping to the solution. The artificial damping is shown to affect the frequency response of the mass-spring model, therefore certain restrictions on the simulation time step must be enforced so that the model produces physically accurate results. The hybrid mathematical model is used to simulate small fibre networks to provide information on the acoustic response of each damage mechanism. The simulated AEs are then analysed using a continuous wavelet transform (CWT), described in [5], which provides a two dimensional time-frequency representation of the signal. The AEs from the two damage mechanisms show different characteristics in the CWT so that it is possible to define a fibre-fibre bond failure by the criteria listed below. The dominant frequency components of the AE must be at approximately 250 kHz or 750 kHz. The strongest frequency component may be at either approximately 250 kHz or 750 kHz. The duration of the frequency component at approximately 250 kHz is longer than that of the frequency component at approximately 750 kHz. Similarly, the criteria for identifying a fibre failure are given below. The dominant frequency component of the AE must be greater than 800 kHz. The duration of the dominant frequency component must be less than 5.00E-06 seconds. The dominant frequency component must be present at the front of the AE. Essentially, the failure of a fibre-fibre bond produces a low frequency wave and the failure of a fibre produces a high frequency pulse. Using this theoretical criteria, it is now possible to train an intelligent classifier such as the Self-Organising Map (SOM) [6] using the experimental data. First certain features must be extracted from the CWTs of the AEs for use in training the SOM. For this work, each CWT is divided into 200 windows of 5E-06s in duration covering a 100 kHz frequency range. The power ratio for each windows is then calculated and used as a feature. Having extracted the features from the AEs, the SOM can now be trained, but care is required so that the both damage mechanisms are adequately represented in the training set. This is an issue with paper as the failure of the fibre-fibre bonds is the prevalent damage mechanism. Once a suitable training set is found, the SOM can be trained and its performance analysed. For the SOM described in this work, there is a good chance that it will correctly classify the experimental AEs.

Constitutive modeling of kinematic-hardening and damage in solder joints

Solder constitutive models are important as they are widely used in FEA simulations to predict the lifetime of soldered assemblies. This paper briefly reviews some common constitutive laws to capture creep in solder and presents work on laws capturing both kinematic hardening and damage. Inverse analysis is used to determine constants for the kinematic hardening law which match experimental creep curves. The mesh dependence of the damage law is overcome by using volume averaging and is applied to predict the crack path in a thermal cycled resistor component

An analysis of the changes to the mechanical and acoustical properties of paper caused by the damage mechanisms present in the fibre structure

This paper will analyse two of the likely damage mechanisms present in a paper fibre matrix when placed under controlled stress conditions: fibre/fibre bond failure and fibre failure. The failure process associated with each damage mechanism will be presented in detail focusing on the change in mechanical and acoustic properties of the surrounding fibre structure before and after failure. To present this complex process mathematically, geometrically simple fibre arrangements will be chosen based on certain assumptions regarding the structure and strength of paper, to model the damage mechanisms. The fibre structures are then formulated in terms of a hybrid vibro-acoustic model based on a coupled mass/spring system and the pressure wave equation. The model will be presented in detail in the paper. The simulation of the simple fibre structures serves two purposes; it highlights the physical and acoustic differences of each damage mechanism before and after failure, and also shows the differences in the two damage mechanisms when compared with one another. The results of the simulations are given in the form of pressure wave contours, time-frequency graphs and the Continuous Wavelet Transform (CWT) diagrams. The analysis of the results leads to criteria by which the two damage mechanisms can be identified. Using these criteria it was possible to verify the results of the simulations against experimental acoustic data. The models developed in this study are of specific practical interest in the paper-making industry, where acoustic sensors may be used to monitor continuous paper production. The same techniques may be adopted more generally to correlate acoustic signals to damage mechanisms in other fibre-based structures.

Thermal-mechanical modelling of power electronic module packaging

In this paper the reliability of the isolation substrate and chip mountdown solder interconnect of power modules under thermal-mechanical loading has been analysed using a numerical modelling approach. The damage indicators such as the peel stress and the accumulated plastic work density in solder interconnect are calculated for a range of geometrical design parameters, and the effects of these parameters on the reliability are studied by using a combination of the finite element analysis (FEA) method and optimisation techniques. The sensitivities of the reliability of the isolation substrate and solder interconnect to the changes of the design parameters are obtained and optimal designs are studied using response surface approximation and gradient optimization method

Lifetime prediction for power electronics module substrate mount-down solder interconnect

A numerical modeling method for the prediction of the lifetime of solder joints of relatively large solder area under cyclic thermal-mechanical loading conditions has been developed. The method is based on the Miner's linear damage accumulation rule and the properties of the accumulated plastic strain in front of the crack in large area solder joint. The nonlinear distribution of the damage indicator in the solder joints have been taken into account. The method has been used to calculate the lifetime of the solder interconnect in a power module under mixed cyclic loading conditions found in railway traction control applications. The results show that the solder thickness is a parameter that has a strong influence on the damage and therefore the lifetime of the solder joint while the substrate width and the thickness of the baseplate are much less important for the lifetime

High current density induced damage mechanisms in electronic solder joints: a state-of-the-art review

High current density induced damages such as electromigration in the on-chip interconnection /metallization of Al or Cu has been the subject of intense study over the last 40 years. Recently, because of the increasing trend of miniaturization of the electronic packaging that encloses the chip, electromigration as well as other high current density induced damages are becoming a growing concern for off-chip interconnection where low melting point solder joints are commonly used. Before long, a huge number of publications have been explored on the electromigration issue of solder joints. However, a wide spectrum of findings might confuse electronic companies/designers. Thus, a review of the high current induced damages in solder joints is timely right this moment. We have selected 6 major phenomena to review in this paper. They are (i) electromigration (mass transfer due electron bombardment), (ii) thermomigration (mass transfer due to thermal gradient), (iii) enhanced intermetallic compound growth, (iv) enhanced current crowding, (v) enhanced under bump metallisation dissolution and (vi) high Joule heating and (vii) solder melting. the damage mechanisms under high current stressing in the tiny solder joint, mentioned in the review article, are significant roadblocks to further miniaturization of electronics. Without through understanding of these failure mechanisms by experiments coupled with mathematical modeling work, further miniaturization in electronics will be jeopardized

Computer simulation of crack propagation in power electronics module solder joints

A numerical modelling method for the analysis of solder joint damage and crack propagation has been described in this paper. The method is based on the disturbed state concept. Under cyclic thermal-mechanical loading conditions, the level of damage that occurs in solder joints is assumed to be a simple monotonic scalar function of the accumulated equivalent plastic strain. The increase of damage leads to crack initiation and propagation. By tracking the evolution of the damage level in solder joints, crack propagation path and rate can be simulated using Finite Element Analysis method. The discussions are focused on issues in the implementation of the method. The technique of speeding up the simulation and the mesh dependency issues are analysed. As an example of the application of this method, crack propagation in solder joints of power electronics modules under cyclic thermal-mechanical loading conditions has been analyzed and the predicted cracked area size after 3000 loading cycles is consistent with experimental results.

Prooxidant action of knipholone anthrone: Copper dependent reactive oxygen species generation and DNA damage

Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological activities including in vitro antioxidant and cytotoxic properties. By using DNA damage as an experimental model, the comparative Cu(II)-dependent prooxidant action of these two compounds were studied. In the presence of Cu(II) ions, the antioxidant KA (3.1-200 [mu]M) but not KP (6-384 [mu]M) caused a concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by KA could be abolished by reactive oxygen species scavengers, glutathione and catalase as well as EDTA and a specific Cu(I) chelator bathocuproine disulfonic acid. In addition to Cu(II) chelating activity, KA readily reduces Cu(II) to Cu(I). Copper-dependent generation of reactive oxygen species and the subsequent macromolecular damage may be involved in the antimicrobial and cytotoxic activity of KA.

Application of regularization methods to damage detection in large scale plane frame structures using incomplete noisy modal data

This paper presents an approach for detecting local damage in large scale frame structures by utilizing regularization methods for ill-posed problems. A direct relationship between the change in stiffness caused by local damage and the measured modal data for the damaged structure is developed, based on the perturbation method for structural dynamic systems. Thus, the measured incomplete modal data can be directly adopted in damage identification without requiring model reduction techniques, and common regularization methods could be effectively employed to solve the developed equations. Damage indicators are appropriately chosen to reflect both the location and severity of local damage in individual components of frame structures such as in brace members and at beam-column joints. The Truncated Singular Value Decomposition solution incorporating the Generalized Cross Validation method is introduced to evaluate the damage indicators for the cases when realistic errors exist in modal data measurements. Results for a 16-story building model structure show that structural damage can be correctly identified at detailed level using only limited information on the measured noisy modal data for the damaged structure.