An active machine learning approach for optimal design of magnesium alloys using Bayesian optimisation.

In the pursuit of magnesium (Mg) alloys with targeted mechanical properties, a multi-objective Bayesian optimisation workflow is presented to enable optimal Mg-alloy design. A probabilistic Gaussian process regressor model was trained through an active learning loop, while balancing the exploration and exploitation trade-off via an acquisition function of the upper confidence bound. New candidate alloys suggested by the optimiser within each iteration were appended to the training data, and the performance of this sequential strategy was validated via a regret analysis. Using the proposed approach, the dependency of the prediction error on the training data was overcome by considering both the predictions and their associated uncertainties. The method developed here, has been packaged into a web tool with a graphical user-interactive interface (GUI) that allows the proposed optimal Mg-alloy design strategy to be deployed.

Projected thickness reconstruction from a single defocused transmission electron microscope image of an amorphous object.

Single defocused transmission electron microscope phase contrast images are used to reconstruct the projected thickness map of a single-material object. The algorithm is non-iterative and stable, and we extend it to account for the presence of spherical aberration in the objective optics. The technique can reconstruct the projected thickness map of general single-material objects in the strong phase/weak amplitude regime. It is sensitive to any excursions in the projected thickness from the average, and ideal for examining voids and free volume accumulation in amorphous/glassy materials at the nanometer scale. The resolution of the technique depends on the choice of defocus and the thickness of the specimen. In a certain regime, we demonstrate that variations in the transverse projected thickness with a lateral diameter of ∼ 0.25 nm may be detected. We use our algorithm to quantitatively reconstruct the projected thickness of latex sphere test specimens from single defocused electron micrographs. We demonstrate that the reconstruction has a large tolerance for error in the input parameters. Simulations confirm that the technique is quantitative, and demonstrate that the origin of low-frequency artifacts is an instability due to noise. We show that the autocorrelation of the projected thickness map may be used to measure the size of open structures in the object using both simulation and latex sphere data.

Measuring the PSF from aperture images of arbitrary shape--an algorithm.

A new algorithm for determining the point spread function (PSF) of digital imaging systems is presented. The input is an image of an aperture whose shape need not be regular. The aperture shape is refined to an effective sub-pixel resolution and the PSF of the system is determined by de-convolution, assuming uniform illumination and a step function edge. The method has been tested on theoretical aperture images of varying shape and PSF, with and without noise. Depending on the degree of noise, a known PSF can be recovered to an accuracy of between 0.2 and 0.8%. Some typical results are given for a Gatan Image Filter with a 794 YAG multiscan camera on a Philips EM 430 transmission electron microscope at 200 and 300 kV. An example of a de-convoluted convergent beam electron diffraction pattern is included. The algorithm tolerates a small amount of de-focus.

Restriction analysis of the structural alpha-L-fucosidase gene and its linkage to fucosidosis.

Human alpha-L-fucosidase is a lysosomal enzyme responsible for hydrolysis of alpha-L-fucoside linkages in fucoglycoconjugates. A single gene, FUCA 1, located on chromosome 1p34.1-1p36.1 encodes for alpha-L-fucosidase activity. To gain insight into the nature of the molecular defects leading to fucosidosis, we have characterized the genomic structure of FUCA 1. Restriction-endonuclease analysis suggests that at least seven exons dispersed over 22 kb are present in genomic FUCA 1. Two restriction-fragment-length polymorphisms (RFLPs) have been identified in the Caucasian population. The PvuII and BglI RFLPs each have two codominant alleles in Hardy-Weinberg equilibrium. Allele frequencies for the PvuII RFLP are .70/.30, and those for the BglI RFLP .63/.37. Both RFLPs are in strong linkage disequilibrium with each other, with a correlation coefficient of .94. The polymorphism information content (PIC) of the combined DNA markers is .38, high enough to be useful in the prenatal diagnosis of fucosidosis. The combined lod score for linkage between the fucosidosis mutation and FUCA 1 markers in two families was significant at a recombination fraction of 0. This suggests that the fucosidosis mutation resides in FUCA 1.

Identification of a mutation in the structural alpha-L-fucosidase gene in fucosidosis.

Fucosidosis is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration and mental retardation. The disease results from deficient activity of alpha-L-fucosidase (E.C.3.2.1.51), a lysosomal enzyme that hydrolyzes fucose from fucoglycoconjugates. In an attempt to identify the mutation(s) that result(s) in fucosidosis, we performed Southern blot analysis of the structural gene encoding alpha-L-fucosidase (FUCA 1) in 23 patients affected with fucosidosis. In five patients Southern blot analysis showed obliteration of an EcoRI restriction site in the open reading frame of FUCA 1 encoding mature alpha-L-fucosidase. This abnormality was not observed in 80 controls, and it may be the basic defect responsible for fucosidosis in these patients. Both patients with the severe type I form of fucosidosis and patients with the less severe type II were shown to be homozygous for this presumed mutation. In the remaining 18 patients the EcoRI site obliteration, major-gene deletions, or insertions were not detected. This suggests that at least two different mutations are involved in fucosidosis. The heterogeneity found at the DNA level was not present at the protein level, as all fucosidosis patients investigated had low fucosidase protein (less than 6% of normal) and negligible fucosidase activity in fibroblasts and lymphoblastoid cell lines.

NsiI and ScaI restriction fragment length polymorphisms at the atrial natriuretic peptides (ANP) gene locus.

The authors report on two new restriction fragment length polymorphisms at the human atrial natriuretic peptide gene locus, detected in three families with restriction endonucleases ScaI and NsiI.