Development of an epileptic seizure prediction algorithm using R–R intervals with self-attentive autoencoder

Epilepsy is a neurological disorder that may affect the autonomic nervous system (ANS) from 15 to 20 min before seizure onset, and disturbances of ANS affect R–R intervals (RRI) on an electrocardiogram (ECG). This study aims to develop a machine learning algorithm for predicting focal epileptic seizures by monitoring R–R interval (RRI) data in real time. The developed algorithm adopts a self-attentive autoencoder (SA-AE), which is a neural network for time-series data. The results of applying the developed seizure prediction algorithm to clinical data demonstrated that it functioned well in most patients; however, false positives (FPs) occurred in specific participants. In a future work, we will investigate the causes of FPs and optimize the developing seizure prediction algorithm to further improve performance using newly added clinical data.

     

Clinicopathological significance of intratubular giant macrophages in progressive glomerulonephritis

Very large macrophages, which we have termed "giant macrophages" (G-M phi), have been found in renal tubules, some containing cytoplasmic vacuoles. To elucidate their pathophysiological roles, we examined renal biopsy tissues from various primary glomerulonephritis (GN) and tubulointerstitial nephritis (TIN) using immunohistochemistry with monoclonal antibodies against M phi and other cell surface markers. Giant macrophages were absent or rare in TIN, minimal change nephrotic syndrome, and minor glomerular abnormalities, but G-M phi was plentiful in progressive glomerulonephrides such as IgA nephropathy with crescents, membranoproliferative GN, focal segmental glomerulosclerosis, and especially in crescentic GN. These G-M phi were usually seen in the lumen of renal tubules, but occasionally were found in the Bowman's spaces and glomerular tufts, and similar cells were also found in urine. Moreover, they frequently made contact with tubular epithelial cells expressing intercellular adhesion molecule-1, and the tubular epithelial cells in such lesions often had degenerative changes. Giant M phi may damage tubular epithelial cells from the luminal side. Phenotypically, G-M phi showed activated (CD71+) and mature (25F9+) characteristics along with features of M phi (CD68+), and the cytoplasm contained a great deal of lipids. The numbers of G-M phi in renal tissues closely correlated with the degree of hematuria (rho = 0.5, P < 0.001), serum creatinine value (r = 0.63, P < 0.001) in GN patients (N = 96) and with proteinuria in IgA nephropathy patients (r = 0.89, P < 0.001, N = 27). These data suggest that G-M phi are M phi that were activated and matured in certain active inflammatory sites, which flowed into tubules and then into urine. Thus, the existence of G-M phi in biopsy tissue or urine reflect the activity of GN and may have a predictive value for the progression of GN.     

Ultra light-weight and high-resolution X-ray mirrors using DRIE and X-ray LIGA techniques for space X-ray telescopes

We are developing novel ultra light-weight and high-resolution X-ray micro pore optics for space X-ray telescopes. In our method, curvilinear micro pore structures are firstly fabricated by silicon deep reactive ion etching (DRIE) or X-ray LIGA processes. Secondly, side walls of the micro structures are smoothed by magnetic field assisted finishing and/or hydrogen annealing techniques for high reflectivity mirrors. Thirdly, to focus parallel X-ray lights from astronomical objects, these structures are elastically or plastically bent into a spherical shape. Fourthly, the bent structures are stacked to form a multi-stage X-ray telescope. In this paper, we report on fabrication and X-ray reflection tests of silicon and nickel X-ray mirrors using the DRIE and LIGA processes, respectively. For the first time, X-ray reflections were confirmed on both of the mirrors. Estimated rms roughnesses were 5 nm and 3 nm for the silicon and nickel mirrors, respectively.     

Compact electrostatic levitator for diffraction measurements with a two axis diffractometer and a laboratory x-ray source

A compact electrostatic levitator was developed for the structural analysis of high-temperature liquids by x-ray diffraction methods. The size of the levitator was 200 mm in diameter and 200 mm in height and can be set up on a two axis diffractometer with a laboratory x-ray source, which is very convenient in performing structural measurements of high-temperature liquids. In particular, since the laboratory x-ray source allows a great amount of user time, preliminary or challenging experiments can be performed with trial and error, which prepares and complements synchrotron x-ray experiments. The present small apparatus also provides the advantage of portability and facility of setting. To demonstrate the capability of this electrostatic levitator, the static structure factors of alumina and silicon samples in their liquid phases were successfully measured.     

Accumulation of triosephosphate isomerase, with sequence homology to Beta amyloid peptides, in vessel walls of the newborn piglet hippocampus

We investigated whether beta-amyloid (Abeta)-like immunoreactivity was seen in the brains of newborn piglets. The immunoreactivity for Abeta(1-42) and Abeta(1-40) proteins, but not Abeta precursor protein, was present in CD68-positive perivascular cells of the hippocampus and in parts of the meninges. It was colocalized with immunoreactivity for receptor for advanced glycation end product and tumor necrosis factor-alpha. The protein with a molecular mass of 27 kDa, which was recognized by the Abeta antibodies, was identified as triosephosphate isomerase (TPI) with sequence homology to Abeta peptides by N-terminal amino acid sequencing, mass fingerprint analysis using matrix-associated laser desorption/ionization mass spectrometry, and Western blotting. Western blotting assay also revealed that detectable expression of Abeta proteins were not seen in the piglet brains. These findings indicate that TPI with sequence homology to Abeta peptides accumulates in perivascular cells of the microglia/macrophage lineage located around arterial vessels of the newborn piglet hippocampus.     

Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study

The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1–3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal β-strand (S6) of the central β-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD.     

Generating Instances for MAX2SAT with Optimal Solutions

A test instance generator (an instance generator for short) for MAX2SAT is a procedure that produces, given a number n of variables, a 2-CNF formula F of n variables (randomly chosen from some reasonably large domain), and simultaneously provides one of the optimal solutions for F. We propose an outline to design an instance generator using an expanding graph of a certain type, called here an "exact 1/2-enlarger". We first show a simple algorithm for constructing an exact 1/2-enlarger, thereby deriving one concrete polynomial-time instance generator GEN. We also show that an exact 1/2-enlarger can be obtained with high probability from graphs randomly constructed. From this fact, we propose another type of instance generator RGEN; it produces a 2-CNF formula with a solution which is optimal for the formula with high probability. However, RGEN produces less structured formulas and a much larger class of formulas than GEN. In fact, we prove the NP-hardness of MAX2SAT over the set of 2-CNF formulas produced by RGEN.