On modifications to the long-term survival mixture model in the presence of competing risks

A mixture model for long-term survivors has been adopted in various fields such as biostatistics and criminology where some individuals may never experience the type of failure under study. It is directly applicable in situations where the only information available from follow-up on individuals who will never experience this type of failure is in the form of censored observations. In this paper, we consider a modification to the model so that it still applies in the case where during the follow-up period it becomes known that an individual will never experience failure from the cause of interest. Unless a model allows for this additional information, a consistent survival analysis will not be obtained. A partial maximum likelihood (ML) approach is proposed that preserves the simplicity of the long-term survival mixture model and provides consistent estimators of the quantities of interest. Some simulation experiments are performed to assess the efficiency of the partial ML approach relative to the full ML approach for survival in the presence of competing risks.

The mechanical properties of Saccharomyces cerevisiae

Cell-wall mechanical properties play an integral part in the growth and form of Saccharomyces cerevisiae, In contrast to the tremendous knowledge on the genetics of S. cerevisiae, almost nothing is known about its mechanical properties. We have developed a micromanipulation technique to measure the force required to burst single cells and have recently established a mathematical model to extract the mechanical properties of the cell wall from such data, Here we determine the average surface modulus of the S, cerevisiae cell wall to be 11.1 +/- 0.6 N/m and 12.9 +/- 0.7 N/m in exponential and stationary phases, respectively, giving corresponding Young's moduli of 112 +/- 6 MPa and 107 +/- 6 MPa, This result demonstrates that yeast cell populations strengthen as they enter stationary phase by increasing wall thickness and hence the surface modulus, without altering the average elastic properties of the cell-wall material. We also determined the average breaking strain of the cell wall to be 82% +/- 3% in exponential phase and 80% +/- 3% in stationary phase, This finding provides a failure criterion that can be used to predict when applied stresses (e,g,, because of fluid flow) will lead to wall rupture, This work analyzes yeast compression experiments in different growth phases by using engineering methodology.

Determination of activation energy distributions for chemisorption of oxygen on carbon: an improved approach

The present paper proposes an approach to obtaining the activation energy distribution for chemisorption of oxygen onto carbon surfaces, while simultaneously allowing for the activation energy dependence of the pre-exponential factor of the rate constant. Prior studies in this area have considered this factor to be uniform, thereby biasing estimated distributions. The results show that the derived activation energy distribution is not sensitive to the chemisorption mechanism because of the step function like property of the coverage. The activation energy distribution is essentially uniform for some carbons, and has two or possibly more discrete stages, suggestive of at least two types of sites, each with its own uniform distribution. The pre-exponential factors of the reactions are determined directly from the experimental data, and are found not to be constant as assumed in earlier work, but correlated with the activation energy. The latter results empirically follow an exponential function, supporting some earlier statistical and experimental work. The activation energy distribution obtained in the present paper permits improved correlation of chemisorption data in comparison to earlier studies. (C) 2000 Elsevier Science Ltd. All rights reserved.

Gender differences in the relationship between depression and suicidal ideation in young adolescents

Objective: This study examined the risk relationship between depressive symptomatology and suicidal ideation for young adolescent males and females. Method: A large cohort of students in their first year of high school completed the Center for Epidemiological Studies Depression Scale (CES-D) and the Adolescent Suicide Questionnaire. The risk relationship between depressive symptomatology and suicidal ideation was modelled using non-parametric kernel-smoothing techniques. Results: Suicidal ideation was more frequently reported by females compared with males which was partly explained by females having higher mean depression scores. At moderate levels of depression females also had a significantly higher risk of suicidal ideation compared with males and this increased risk contributed to the overall higher levels of female ideation. Conclusions: The risk relationship between depressive symptomatology and suicidal ideation is different for young adolescent males and females. The results indicate that moderate levels of depressive symptomatology can be associated with suicidal ideation (especially among young females) and that for these young people a suicide risk assessment is required.

Computational immunology: The coming of age

The explosive growth in biotechnology combined with major advancesin information technology has the potential to radically transformimmunology in the postgenomics era. Not only do we now have readyaccess to vast quantities of existing data, but new data with relevanceto immunology are being accumulated at an exponential rate. Resourcesfor computational immunology include biological databases and methodsfor data extraction, comparison, analysis and interpretation. Publiclyaccessible biological databases of relevance to immunologists numberin the hundreds and are growing daily. The ability to efficientlyextract and analyse information from these databases is vital forefficient immunology research. Most importantly, a new generationof computational immunology tools enables modelling of peptide transportby the transporter associated with antigen processing (TAP), modellingof antibody binding sites, identification of allergenic motifs andmodelling of T-cell receptor serial triggering.

Infiltration from surface and buried point sources: The average wetting water content

The assumption in analytical solutions for flow from surface and buried point sources of an average water content, (θ) over bar, behind the wetting front is examined. Some recent work has shown that this assumption fitted some field data well. Here we calculated (θ) over bar using a steady state solution based on the work by Raats [1971] and an exponential dependence of the diffusivity upon the water content. This is compared with a constant value of (θ) over bar calculated from an assumption of a hydraulic conductivity at the wetting front of 1 mm day(-1) and the water content at saturation. This comparison was made for a wide range of soils. The constant (θ) over bar generally underestimated (θ) over bar at small wetted radii and overestimated (θ) over bar at large radii. The crossover point between under and overestimation changed with both soil properties and flow rate. The largest variance occurred for coarser texture soils at low-flow rates. At high-flow rates in finer-textured soils the use of a constant (θ) over bar results in underestimation of the time for the wetting front to reach a particular radius. The value of (θ) over bar is related to the time at which the wetting front reaches a given radius. In coarse-textured soils the use of a constant value of (θ) over bar can result in an error of the time when the wetting front reaches a particular radius, as large as 80% at low-flow rates and large radii.

Use of bulk density profiles from X-radiography to examine structural crust models

Exponential and sigmoidal functions have been suggested to describe the bulk density profiles of crusts. The present work aims to evaluate these conceptual models using high resolution X-radiography. Repacked seedbeds from two soil materials, air-dried or prewetted by capillary rise, were subjected to simulated rain, which resulted in three types of structural crusts, namely, slaking, infilling, and coalescing. Bulk density distributions with depth were generated using high-resolution (70 mum), calibrated X-ray images of slices from the resin-impregnated crusted seedbeds. The bulk density decreased progressively with depth, which supports the suggestion that a crust should be considered as a nonuniform layer. For the slaking and the coalescing crusts, the exponential function underestimated the strong change in bulk density across the morphologically defined transition between the crust and the underlying material; the sigmoidal function provided a better description. Neither of these crust models effectively described the shape of the bulk density profiles through the whole seedbed. Below the infilling and slaking crusts, bulk density increased linearly with depth as a result of slumping. In the coalescing crusted seedbed, the whole seedbed uniformly collapsed and most of the bulk density change within the crust could be ascribed to slumping (0.33 g cm(-3)) rather than to crusting (0.12 g cm(-3)). Finally, (i) X-radiography appears as a unique tool to generate high resolution bulk density profiles and (ii) in structural crusts, bulk density profiles could be modeled using the existing exponential and sigmoidal crusting models, provided a slumping model would be coupled.

Cumulative sedimentation analysis of Escherichia coli debris size

A new method to measure Escherichia coil cell debris size after homogenization is presented. It is based on cumulative sedimentation analysis under centrifugal force, coupled with Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis of sedimented proteins. The effects that fermentation and homogenization conditions have on the resulting debris distributions were investigated using this method. Median debris size decreased significantly from approximately 0.5 mu m to 0.3 mu m as the number of homogenization passes increased from 2 to 10. Under identical homogenization conditions, uninduced host cells in stationary phase had a larger debris size than exponential cells after 5 homogenizer passes. This difference was not evident after 2 or in passes, possibly because of confounding intact cells and the existence of a minimum debris size for the conditions investigated. Recombinant cells containing protein inclusion bodies had the smallest debris size following homogenization. The method was also used to measure the size distribution of inclusion bodies. This result compared extremely well with an independent determination using centrifugal disc photosedimentation (CDS), thus validating the method. This is the first method that provides accurate size distributions of E. coli debris without the need for sample pretreatment, theoretical approximations (e.g. extinction coefficients), or the separation of debris and inclusion bodies prior to analysis. (C) 1997 John Wiley & Sons, Inc.

Structure optimization combining soft-core interaction functions, the diffusion equation method, and molecular dynamics

Smoothing the potential energy surface for structure optimization is a general and commonly applied strategy. We propose a combination of soft-core potential energy functions and a variation of the diffusion equation method to smooth potential energy surfaces, which is applicable to complex systems such as protein structures; The performance of the method was demonstrated by comparison with simulated annealing using the refinement of the undecapeptide Cyclosporin A as a test case. Simulations were repeated many times using different initial conditions and structures since the methods are heuristic and results are only meaningful in a statistical sense.

The subcycled Newmark algorithm

The popular Newmark algorithm, used for implicit direct integration of structural dynamics, is extended by means of a nodal partition to permit use of different timesteps in different regions of a structural model. The algorithm developed has as a special case an explicit-explicit subcycling algorithm previously reported by Belytschko, Yen and Mullen. That algorithm has been shown, in the absence of damping or other energy dissipation, to exhibit instability over narrow timestep ranges that become narrower as the number of degrees of freedom increases, making them unlikely to be encountered in practice. The present algorithm avoids such instabilities in the case of a one to two timestep ratio (two subcycles), achieving unconditional stability in an exponential sense for a linear problem. However, with three or more subcycles, the trapezoidal rule exhibits stability that becomes conditional, falling towards that of the central difference method as the number of subcycles increases. Instabilities over narrow timestep ranges, that become narrower as the model size increases, also appear with three or more subcycles. However by moving the partition between timesteps one row of elements into the region suitable for integration with the larger timestep these the unstable timestep ranges become extremely narrow, even in simple systems with a few degrees of freedom. As well, accuracy is improved. Use of a version of the Newmark algorithm that dissipates high frequencies minimises or eliminates these narrow bands of instability. Viscous damping is also shown to remove these instabilities, at the expense of having more effect on the low frequency response.

Metastable chaos in the ammonia ring laser

We report experimental studies of metastable chaos in the far-infrared ammonia ring: laser. When the laser pump power is switched from above chaos threshold to slightly below, chaotic intensity pulsations continue for a varying time afterward before decaying to either periodic or cw emission. The behavior is in good qualitative agreement with that predicted by the Lorenz equations, previously used to describe this laser. The statistical distribution of the duration of the chaotic transient is measured and shown to be in excellent agreement with the Lorenz equations in showing a modified exponential distribution. We also give a brief numerical analysis and graphical visualization of the Lorenz equations in phase space illustrating the boundary between the metastable chaotic and the stable fixed point basins of attraction. This provides an intuitive understanding of the metastable dynamics of the Lorenz equations and the experimental system.

Modeling of subcutaneous absorption kinetics of infusion solutions in the elderly using technetium

Absorption kinetics of solutes given with the subcutaneous administration of fluids is ill-defined. The gamma emitter, technitium pertechnetate, enabled estimates of absorption rate to be estimated independently using two approaches. In the first approach, the counts remaining at the site were estimated by imaging above the subcutaneous administration site, whereas in the second approach, the plasma technetium concentration-time profiles were monitored up to 8 hr after technetium administration. Boluses of technetium pertechnetate were given both intravenously and subcutaneously on separate occasions with a multiple dosing regimen using three doses on each occasion. The disposition of technetium after iv administration was best described by biexponential kinetics with a V-ss of 0.30 +/- 0.11 L/kg and a clearance of 30.0 +/- 13.1 ml/min. The subcutaneous absorption kinetics was best described as a single exponential process with a half-life of 18.16 +/- 3.97 min by image analysis and a half-life of 11.58 +/- 2.48 min using plasma technetium time data. The bioavailability of technetium by the subcutaneous route was estimated to be 0.96 +/- 0.12. The absorption half-life showed no consistent change with the duration of the subcutaneous infusion. The amount remaining at the absorption site with time was similar when analyzed using image analysis, and plasma concentrations assuming multiexponential disposition kinetics and a first-order absorption process. Profiles of fraction remaining at the absorption sire generated by deconvolution analysis, image analysis, and assumption of a constant first-order absorption process were similar. Slowing of absorption from the subcutaneous administration site is apparent after the last bolus dose in three of the subjects and can De associated with the stopping of the infusion. In a fourth subject, the retention of technetium at the subcutaneous site is more consistent with accumulation of technetium near the absorption site as a result of systemic recirculation.

On the decay rates of buffers in continuous flow lines

Consider a tandem system of machines separated by infinitely large buffers. The machines process a continuous flow of products, possibly at different speeds. The life and repair times of the machines are assumed to be exponential. We claim that the overflow probability of each buffer has an exponential decay, and provide an algorithm to determine the exact decay rates in terms of the speeds and the failure and repair rates of the machines. These decay rates provide useful qualitative insight into the behavior of the flow line. In the derivation of the algorithm we use the theory of Large Deviations.

The radical homopolymerization of N-phenylmaleimide, N-n-hexylmaleimide and N-cyclohexylmaleimide in tetrahydrofuran

The kinetics and mechanisms of thermally initiated (using 2,2'-azobisisoburyronitrile (AIBN) as initiator) radical homopolymerizations of a series of maleimides, including N-phenymaleimide (PHMI) [l-phenyl-1H-pyrrole-2,5-dione]; N-n-hexylmaleimide (nHMI) [l-(n-hexyI)-1H-pyrrole-2,5-dione]; and N-cyclohexylmaIeimide (CHMI) [l-cyclohexyl- 1H-pyrrole-2,5-dione] have been investigated in THF solution by an on-line FT-NIR technique. It was found that the order of the activation energies for the three N-sub-MIs is: E-a PHMI < E-a (PHMI) < E-a (CHMI). The overall polymerization rate parameter k and the pre-exponential factor A were calculated. The kinetic order with respect to the N-sub-MIs was in the range of 0.71 < m < 0.75 for the initiator and n = 1.0 for the monomer. Radical transfer to solvent was found to be the key factor in determining the apparent order with respect to the initiator. All of the homopolymers had a relatively low molecular weight. The end groups of the polymer chains were characterized by MALDI-TOF, GPC and NMR methods and the results clearly indicate that the polymerization was initiated by THF radicals, and that the termination reaction is mainly controlled by chain transfer to solvent through an hydrogen abstraction mechanism. (C) 2001 Elsevier Science Ltd. All rights reserved.

Time evolution in the unimolecular master equation at low temperatures: full spectral solution with scalable iterative methods and high precision

A new method is presented to determine an accurate eigendecomposition of difficult low temperature unimolecular master equation problems. Based on a generalisation of the Nesbet method, the new method is capable of achieving complete spectral resolution of the master equation matrix with relative accuracy in the eigenvectors. The method is applied to a test case of the decomposition of ethane at 300 K from a microcanonical initial population with energy transfer modelled by both Ergodic Collision Theory and the exponential-down model. The fact that quadruple precision (16-byte) arithmetic is required irrespective of the eigensolution method used is demonstrated. (C) 2001 Elsevier Science B.V. All rights reserved.