Tests of an adaptive QM/MM calculation on free energy profiles of chemical reactions in solution.

We present reaction free energy calculations using the adaptive buffered force mixing quantum mechanics/molecular mechanics (bf-QM/MM) method. The bf-QM/MM method combines nonadaptive electrostatic embedding QM/MM calculations with extended and reduced QM regions to calculate accurate forces on all atoms, which can be used in free energy calculation methods that require only the forces and not the energy. We calculate the free energy profiles of two reactions in aqueous solution: the nucleophilic substitution reaction of methyl chloride with a chloride anion and the deprotonation reaction of the tyrosine side chain. We validate the bf-QM/MM method against a full QM simulation, and show that it correctly reproduces both geometrical properties and free energy profiles of the QM model, while the electrostatic embedding QM/MM method using a static QM region comprising only the solute is unable to do so. The bf-QM/MM method is not explicitly dependent on the details of the QM and MM methods, so long as it is possible to compute QM forces in a small region and MM forces in the rest of the system, as in a conventional QM/MM calculation. It is simple, with only a few parameters needed to control the QM calculation sizes, and allows (but does not require) a varying and adapting QM region which is necessary for simulating solutions.

Boundary conditions in physical model tests-the influence of deck pinning on the response of piled bridge abutments in laterally spreading soils

Physical models are widely used in the study of geotechnical earthquake engineering phenomena, and the comparison of modelling results to observations from field reconnaissance provides a transparent means of evaluating the design of our physical models. This paper compares centrifuge tests of pile groups in laterally spreading slopes with the response of piled bridge abutments in the 2011 Christchurch earthquake. We show that the model foundation's fixity conditions strongly affect the success with which the mechanism of response of the real abutments is replicated in the tests. © 2012 American Society of Civil Engineers.

High-performance bowing machine tests of bowed-string transients

The development is described of a computer-controlled bowing machine that can bow a string with a range of gestures that match or exceed the capabilities of a human violinist. Example measurements of string vibration under controlled bowing conditions are shown, including a Schelleng diagram and a set of Guettler diagrams, for the open D string of a cello. For some results a rosin-coated rod was used in place of a conventional bow, to provide quantitative data for comparison with theoretical predictions. The results show qualitative consistency with the predictions of Schelleng and Guettler, but details are revealed that go beyond the limitations of existing models. © S. Hirzel Verlag · EAA.

Permutation Tests for Classification

We introduce and explore an approach to estimating statistical significance of classification accuracy, which is particularly useful in scientific applications of machine learning where high dimensionality of the data and the small number of training examples render most standard convergence bounds too loose to yield a meaningful guarantee of the generalization ability of the classifier. Instead, we estimate statistical significance of the observed classification accuracy, or the likelihood of observing such accuracy by chance due to spurious correlations of the high-dimensional data patterns with the class labels in the given training set. We adopt permutation testing, a non-parametric technique previously developed in classical statistics for hypothesis testing in the generative setting (i.e., comparing two probability distributions). We demonstrate the method on real examples from neuroimaging studies and DNA microarray analysis and suggest a theoretical analysis of the procedure that relates the asymptotic behavior of the test to the existing convergence bounds.

Generating Circuit Tests by Exploiting Designed Behavior

This thesis describes two programs for generating tests for digital circuits that exploit several kinds of expert knowledge not used by previous approaches. First, many test generation problems can be solved efficiently using operation relations, a novel representation of circuit behavior that connects internal component operations with directly executable circuit operations. Operation relations can be computed efficiently by searching traces of simulated circuit behavior. Second, experts write test programs rather than test vectors because programs are more readable and compact. Test programs can be constructed automatically by merging program fragments using expert-supplied goal-refinement rules and domain-independent planning techniques.

Winkler springs (p-y curves) for liquefied soil from element tests.

In practice, piles are most often modelled as "Beams on Non-Linear Winkler Foundation" (also known as “p-y spring” approach) where the soil is idealised as p-y springs. These p-y springs are obtained through semi-empirical approach using element test results of the soil. For liquefied soil, a reduction factor (often termed as p-multiplier approach) is applied on a standard p-y curve for the non-liquefied condition to obtain the p-y curve liquefied soil condition. This paper presents a methodology to obtain p-y curves for liquefied soil based on element testing of liquefied soil considering physically plausible mechanisms. Validation of the proposed p-y curves is carried out through the back analysis of physical model tests.

Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization.

BACKGROUND: Serologic methods have been used widely to test for celiac disease and have gained importance in diagnostic definition and in new epidemiologic findings. However, there is no standardization, and there are no reference protocols and materials. METHODS: The European working group on Serological Screening for Celiac Disease has defined robust noncommercial test protocols for immunoglobulin (Ig)G and IgA gliadin antibodies and for IgA autoantibodies against endomysium and tissue transglutaminase. Standard curves were linear in the decisive range, and intra-assay variation coefficients were less than 5% to 10%. Calibration was performed with a group reference serum. Joint cutoff limits were used. Seven laboratories took part in the final collaborative study on 252 randomized sera classified by histology (103 pediatric and adult patients with active celiac disease, 89 disease control subjects, and 60 blood donors). RESULTS: IgA autoantibodies against endomysium and tissue transglutaminase rendered superior sensitivity (90% and 93%, respectively) and specificity (99% and 95%, respectively) over IgA and IgG gliadin antibodies. Tissue transglutaminase antibody testing showed superior receiver operating characteristic performance compared with gliadin antibodies. The K values for interlaboratory reproducibility showed superiority for IgA endomysium (0.93) in comparison with tissue transglutaminase antibodies (0.83) and gliadin antibodies (0.82 for IgG, 0.62 for IgA). CONCLUSIONS: Basic criteria of standardization and quality assessment must be fulfilled by any given test protocol proposed for serologic investigation of celiac disease. The working group has produced robust test protocols and reference materials available for standardization to further improve reliability of serologic testing for celiac disease.

Typical delay determines waiting time on periodic-food schedules: Static and dynamic tests.

Pigeons and other animals soon learn to wait (pause) after food delivery on periodic-food schedules before resuming the food-rewarded response. Under most conditions the steady-state duration of the average waiting time, t, is a linear function of the typical interfood interval. We describe three experiments designed to explore the limits of this process. In all experiments, t was associated with one key color and the subsequent food delay, T, with another. In the first experiment, we compared the relation between t (waiting time) and T (food delay) under two conditions: when T was held constant, and when T was an inverse function of t. The pigeons could maximize the rate of food delivery under the first condition by setting t to a consistently short value; optimal behavior under the second condition required a linear relation with unit slope between t and T. Despite this difference in optimal policy, the pigeons in both cases showed the same linear relation, with slope less than one, between t and T. This result was confirmed in a second parametric experiment that added a third condition, in which T + t was held constant. Linear waiting appears to be an obligatory rule for pigeons. In a third experiment we arranged for a multiplicative relation between t and T (positive feedback), and produced either very short or very long waiting times as predicted by a quasi-dynamic model in which waiting time is strongly determined by the just-preceding food delay.

Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.

Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.