Arthur Norberg, the Charles Babbage Institute, and the History of Computing

This issue of the IEEE annals of the history of computing originated with a desire to mark the retirement of Charles Babbage Institute founding director Arthur Norberg. In so doing, a number of Norberg's peers were invited to help celebrate and honor the CBI director's career while also appraising the history of computing field that Norberg helped create.     

The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8⁺ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms’ Tumor 1 (WT1) antigen over the disease course (two points at MPE^1st and 2^nd, two months after MPE1^st). Epithelial cell adhesion molecule (EpCAM)⁺ cancer cells (PD-L1⁻ or T cell immunoglobulin mucin-3, TIM-3⁻), both PD-1 or TIM-3 positive CD8⁺ T cells, and CD14⁺CD68⁺CD163⁺TIM-3⁺ macrophages increased from the MPE^1st to MPE^2nd. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8⁺ T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T_CM) of WT1-CTLs was decreased. On the other hand, CD8⁺ T cells in response to SMAD4^P130L, which is homogeneously expressed in EpCAM⁺ cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8⁺ T cell response to SMAD4^P130L was diminished following remarkably decreased numbers of CD8⁺ T_CM in MPE samples. In conclusion, CD8⁺ T cells responding to WT1 or SMAD4^P130L neoantigen expressed in EpCAM⁺ pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.     

Involvement of Atopic Dermatitis in the Development of Systemic Inflammatory Diseases

The skin is recognized as a peripheral lymphoid organ that plays an essential defensive action against external environmental stimuli. However, continuous stimulation of these factors causes chronic inflammation at the local site and occasionally causes tissue damage. Chronic inflammation is recognized as a trigger for systemic organ inflammation. Atopic dermatitis (AD) is a chronic inflammatory skin disease that is influenced by various external environmental factors, such as dry conditions, chemical exposure, and microorganisms. The pathogenesis of AD involves various Th2 and proinflammatory cytokines. Recently updated studies have shown that atopic skin-derived cytokines influence systemic organ function and oncogenesis. In this review, we focus on AD’s influence on the development of systemic inflammatory diseases and malignancies.     

Solving parity games by a reduction to SAT

This paper presents a reduction from the problem of solving parity games to the satisfiability problem in propositional logic (SAT). The reduction is done in two stages, first into difference logic, i.e. SAT combined with the theory of integer differences, an instance of the SAT modulo theories (SMT) framework. In the second stage the integer variables and constraints of the difference logic encoding are replaced with a set of Boolean variables and constraints on them, giving rise to a pure SAT encoding of the problem. The reduction uses Jurdziński?s characterisation of winning strategies via progress measures. The reduction is motivated by the success of SAT solvers in symbolic verification, bounded model checking in particular. The paper reports on prototype implementations of the reductions and presents some experimental results.     

DNA‐Templated Synthesis of Perylenediimide Stacks Utilizing Abasic Sites as Binding Pockets and Reactive Sites

DNA is considered to be a promising biomolecule as a template and scaffold for arranging and organizing functional molecules on the nanoscale. The construction and evaluation of DNAs containing multiple functional molecules that are useful for optoelectronic devices and sensors has been studied. In this paper we report the efficient incorporation of perylenediimide (PDI) units into DNA by using abasic sites both as binding sites and as reactive sites and the construction of PDI stacks within the DNA structure, accomplished through the preorganization of the PDI units in the hydrophobic pocket within the DNA. Our approach could become a valuable method for construction of DNA/chromophore hybrid structures potentially useful for the design of DNA‐based devices and biosensors.     

Seismic proof test of a reinforced concrete containment vessel (RCCV): Part 2: Results of shaking table tests

A 1/8-scale model was constructed of a reinforced concrete containment vessel (RCCV) used in the latest advanced boiling water reactors (ABWR). Shaking table tests were conducted on it with input motions corresponding to or exceeding a design earthquake assumed for a real Nuclear Power Plant.The objectives of the tests were to verify the structural integrity and the leak-proof functional soundness of the RCCV subjected to design earthquakes, and to determine the ultimate strength and seismic margin by an excitation that led to the model's collapse. The model, the test sequence and the pressure and leak test results were addressed in Part 1. The shaking table test method, the input motions and the test results, including the transition of the model's stiffness, natural frequencies and damping factors and the effects of vertical input motions and internal pressure on the model's characteristics and behavior, the load–deformation, the ultimate strength, the failure mode of the reinforced concrete portion and the liner plate are described here. The seismic safety margin that was evaluated by the energy input during the failure test to a design basis earthquake will be described in Part 3. The analytical results of simulation using the multi-lumped mass model will be described in Part 4.     

Optical-fibre network system for air-pollution monitoring over a wide area by optical absorption method

A low-loss optical-fibre network system for monitoring air pollution and species concentrations in various environments utilising the differential absorption method is proposed and discussed as a sensitive and economical as well as nonhazardous method. Its feasibility and advantages are also described on the basis of the present state of the art of the relevant technology.     

Deletion and insertion of a 192-residue peptide in the active-site domain of glycosyl hydrolase family-2 beta-galactosidases

The monomeric multimetal-binding beta-galactosidase of Saccharopolyspora rectivirgula (srbg), a glycosyl hydrolase family-2 enzyme, has a unique sequence consisting of 192 amino acid residues with no similarity to known proteins. This 192-residue sequence (termed the "iota [iota] sequence") appears to be inserted into a sequence homologous to the active-site domain of the Escherichia coli lacZ enzyme (lacZbg). To assess the effects of the t sequence at specific sites of beta-galactosidase on the catalytic functioning and molecular properties of beta-galactosidase, deletion or insertion mutants of beta-galactosidases were constructed, expressed in LacZ- E. coli strains, and characterized: srbgdelta in which the iota sequence was deleted from srbg, and lacZbgI, in which the 192-residue iota sequence was inserted into the corresponding position (between Asp591 and Phe592) in the active-site domain of lacZbg. srbgdelta was a catalytically inactive, dimeric protein which retained multimetal-binding characteristics, suggesting that the iota sequence is very important for maintaining the structure necessary for the catalytic functioning and the monomeric structure of srbg but is not responsible for the unique metal ion requirements of srbg. On the other hand, lacZbgI existed as a mixture of a monomer, a tetramer, and higher multimers. The monomeric species was inactive, whereas the tetramer and other multimers were catalytically active (V(max )K(m) value, 25% of that of lacZbg) and highly specific for beta-D-galactoside. The tetrameric lacZbgI was activated by Mg2+ and Mn2+ with lowered metal affinities, and the stoichiometry of metal binding was unchanged from that of lacZbg. These results, along with the published stereo structure of lacZbg, suggest that, in lacZbgI, the inserted 192-residue iota peptide could fold independently of the lacZbg domains into a "sub-domain," lying distant from the active site and subunit interfaces.     

Seismic proof test of a reinforced concrete containment vessel (RCCV): Part 1: Test model and pressure test

In Japan, the Nuclear Power Engineering Corporation (NUPEC), sponsored by the Ministry of Economy, Trade and Industry (METI), has been conducting a series of seismic reliability proving tests using full-scale or close to full-scale models to simulate actual important equipment that is critical for seismic safety of nuclear power plants. The tests are intended to validate the seismic design and reliability with a sufficient margin even under destructive earthquakes. A series of tests was carried out on a reinforced concrete containment vessel (RCCV) for advanced boiling water reactor (ABWR) from 1992 to 1999. A large-scale high-performance shaking table at Tadotsu Engineering Laboratory, the largest in the world, was used for this test. Part 1 reports the test model and the results of pressure and leak tests. Part 2 describes test procedures, input waves and the results of verification tests such as changes of stiffness, characteristic frequency and damping ratio, the failure of the model and the load deflection. Part 3 shows the seismic safety margin that was evaluated from the energy input during the failure test to a design basis earthquake. Part 4 reports simulation analysis results by a stick model with lumped masses.