An Arnoldi-based preconditioner for iterated Tikhonov regularization

Many problems in science and engineering give rise to linear systems of equations that are commonly referred to as large-scale linear discrete ill-posed problems. These problems arise, for instance, from the discretization of Fredholm integral equations of the first kind. The matrices that define these problems are typically severely ill-conditioned and may be rank-deficient. Because of this, the solution of linear discrete ill-posed problems may not exist or be very sensitive to perturbations caused by errors in the available data. These difficulties can be reduced by applying Tikhonov regularization. We describe a novel "approximate Tikhonov regularization method" based on constructing a low-rank approximation of the matrix in the linear discrete ill-posed problem by carrying out a few steps of the Arnoldi process. The iterative method so defined is transpose-free. Our work is inspired by a scheme by Donatelli and Hanke, whose approximate Tikhonov regularization method seeks to approximate a severely ill-conditioned block-Toeplitz matrix with Toeplitz-blocks by a block-circulant matrix with circulant-blocks. Computed examples illustrate the performance of our proposed iterative regularization method

Range restricted iterative methods for linear discrete ill-posed problems

Linear systems of equations with a matrix whose singular values decay to zero with increasing index number, and without a significant gap, are commonly referred to as linear discrete ill-posed problems. Such systems arise, e.g., when discretizing a Fredholm integral equation of the first kind. The right-hand side vectors of linear discrete ill-posed problems that arise in science and engineering often represent an experimental measurement that is contaminated by measurement error. The solution to these problems typically is very sensitive to this error. Previous works have shown that error propagation into the computed solution may be reduced by using specially designed iterative methods that allow the user to select the subspace in which the approximate solution is computed. Since the dimension of this subspace often is quite small, its choice is important for the quality of the computed solution. This work describes algorithms for three iterative methods that modify the GMRES, block GMRES, and global GMRES methods for the solution of appropriate linear systems of equations. We contribute to the work already available on this topic by introducing two block variants for the solution of linear systems of equations with multiple right-hand side vectors. The dominant computational aspects are discussed, and software for each method is provided. Additionally, we illustrate the utility of these iterative subspace methods through numerical examples focusing on image reconstruction. This paper is accompanied by software

Impact of Immunization Technology and Assay Application on Antibody Performance – A Systematic Comparative Evaluation

Antibodies are quintessential affinity reagents for the investigation and determination of a protein's expression patterns, localization, quantitation, modifications, purification, and functional understanding. Antibodies are typically used in techniques such as Western blot, immunohistochemistry (IHC), and enzyme-linked immunosorbent assays (ELISA), among others. The methods employed to generate antibodies can have a profound impact on their success in any of these applications. We raised antibodies against 10 serum proteins using 3 immunization methods: peptide antigens (3 per protein), DNA prime/protein fragment-boost (“DNA immunization”; 3 per protein), and full length protein. Antibodies thus generated were systematically evaluated using several different assay technologies (ELISA, IHC, and Western blot). Antibodies raised against peptides worked predominantly in applications where the target protein was denatured (57% success in Western blot, 66% success in immunohistochemistry), although 37% of the antibodies thus generated did not work in any of these applications. In contrast, antibodies produced by DNA immunization performed well against both denatured and native targets with a high level of success: 93% success in Western blots, 100% success in immunohistochemistry, and 79% success in ELISA. Importantly, success in one assay method was not predictive of success in another. Immunization with full length protein consistently yielded the best results; however, this method is not typically available for new targets, due to the difficulty of generating full length protein. We conclude that DNA immunization strategies which are not encumbered by the limitations of efficacy (peptides) or requirements for full length proteins can be quite successful, particularly when multiple constructs for each protein are used

Long-term persistent infection of swine monocytes/macrophages with African swine fever virus.

Long-term persistent infection was established in 100% of pigs (n = 19) experimentally infected with African swine fever virus (ASFV). Viral DNA was detected in peripheral blood mononuclear leukocytes (PBML) at greater than 500 days postinfection by a PCR assay. Infectious virus was not, however, isolated from the same PBML samples. In cell fractionation studies of PBML, monocytes/macrophages were found to harbor viral DNA during the persistent phase of infection. This result indicates that monocytes/macrophages are persistently infected with ASFV and that ASFV-swine monocyte/macrophage interactions can result in either lytic or persistent infection

Characterization of P30, a highly antigenic membrane and secreted protein of African swine fever virus

We have identified and characterized a 30-kDa phosphoprotein (p30) of African Swine Fever Virus (ASFV) that is synthesized, membrane localized, and released into the culture medium at early times after infection. Sequence analysis of the p30 open reading frame predicts a highly antigenic protein with putative phosphorylation, glycosylation, and membrane attachment sites. © 1992

Protection of European domestic pigs from virulent African isolates of African swine fever virus by experimental immunisation

African swine fever (ASF) is an acute haemorrhagic disease of domestic pigs for which there is currently no vaccine. We showed that experimental immunisation of pigs with the non-virulent OURT88/3 genotype I isolate from Portugal followed by the closely related virulent OURT88/1 genotype I isolate could confer protection against challenge with virulent isolates from Africa including the genotype I Benin 97/1 isolate and genotype X Uganda 1965 isolate. This immunisation strategy protected most pigs challenged with either Benin or Uganda from both disease and viraemia. Cross-protection was correlated with the ability of different ASFV isolates to stimulate immune lymphocytes from the OURT88/3 and OURT88/1 immunised pigs