Amyloid beta-protein deposition in the leptomeninges and cerebral cortex

To further investigate the process of amyloid beta-protein (Abeta) deposition, we determined, using sensitive enzyme immunoassays, the levels of Abeta40 and Abeta42 (Abetas) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptomeningeal vessels) and cerebral cortices from elderly control subjects showing various stages of Abeta deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble Abeta levels were higher by orders of magnitude than soluble Abeta levels. Soluble Abeta levels in cortices were much lower than those in leptomeninges. In insoluble Abeta in the cortex, Abeta42 was by far the predominant species, and Abeta42 in AD cortices was characterized by the highest degree of modifications in the amino terminus. In contrast, this Abeta42 predominance was not observed in insoluble Abeta in the leptomeninges, which were found to be able to accumulate Abetas to an extent similar to that in the cortex, on a weight basis. The levels of insoluble Abeta in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively. However, the presence of plaque-free cortical samples showing significant levels of insoluble Abeta42 suggests that biochemically detectable Abeta accumulation precedes immunocytochemically detectable Abeta deposition in the cortex.     

Dielectric properties above the glass transition for a series of epoxide prepolymers

Dielectric properties above the glass transition have been investigated for a series of bisphenol-A type epoxide prepolymers (388 ≤ M?_w ≤ 2640). Dielectric measurements were performed over a frequency range of 50 Hz–1 MHz using a vertical parallel plate cell which was constructed in the laboratory. The dielectric α-relaxation for each prepolymer fits the empirical model of the Havriliak–Negami equation. The temperature dependence of the dielectric relaxation time τ is described by the Williams–Landel–Ferry (WLF) equation as well as that of the direct current conductivity σ, which can be measured using the same cell. The relationship between τ and σ, σ^· τ^m = const, is derived from experimental results. The exponent m, which depends on the molecular weight of the prepolymer, is considered to correspond to the ratio of the segmental mobility to ionic mobility. The dielectric loss ε″ can be used as an indicator of the direct current conduction in the temperatures where the ionic component in ε″ becomes much larger than the dipole one.     

Antitumor activity of synthetic alkylphospholipids with or without PAF activity

1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) has been reported to possess definite antitumor activity in vivo. Twenty-two alkyl lysophospholipid analogs were chemically synthesized, and their antitumor activity against mouse experimental tumors (Sarcoma 180, MM46, P388) was examined. Among them, 1-O-octadecyl-2-O-acetoacetyl-rac-glycerol-3-phosphocholine was found to show antitumor activity similar to ET-18-OMe with less acute toxicity. Intravenous injection of the ET-18-OMe withsn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by thesn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as platelet-activating factor (PAF) agonists. The acetoacetyl compound, another PAF agonist, showed similar stereospecific antitumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF receptor. Our preliminary results indicated that the responsible cells under these conditions might be primarily immature macrophages present in the bone marrow. No appreciable or even adverse stereospecificity was observed in the different sets of experiments where the activity of ET-18-OMe against MM46 tumor cells in vivo or the direct cytotoxicity against human promyelocytic leukemia HL-60 cells in vitro was examined. Under, some conditions, the antitumor activity of ET-18-OMe in vivo may be revealed through direct cytotoxicity and/or modulation of the host defense system by “nonspecific” mechanisms. Some alkylphospholipids without PAF activity may also show antitumor activity through similar, “nonspecific” mechanisms.     

Effect of inorganic salt on adsorption of sodium alkyl sulfates and fatty acid sodium salts from aqueous solution onto ion exchange resins

The adsorption isotherms of sodium salts of alkyl sulfonic acid and fatty acid with various carbon numbers onto ion exchange resins were measured in the absence and in the presence of sodium chloride in aqueous solutions. In the absence of the inorganic salt, the amount of adsorption remarkably increased with an increase in the length of alkyl groups in the adsorbates. Furthermore, the amount of adsorption apparently decreased with addition of sodium chloride into the solutions and almost reached a constant value at high concentrations of NaCl. This behavior strongly suggested that the electrostatic interaction on the adsorption decreased with increasing salt concentration and that the effect of hydrophobic interaction seems to play an important role on adsorption.     

Guinea pig bone marrow cells treated with platelet-activating factor generate factor(s) which affects their DNA synthesis and microbicidal activity

We have previously reported that platelet-activating factor (PAF) induces proliferation and microbicidal activity of guinea pig bone marrow cells. In the present study, we have found that the conditioned medium of PAF- or nonmetabolizable PAF agonist-treated guinea pig bone marrow cells augmented DNA synthesis and induced microbicial activity of bone marrow cells. A PAF specific antagonist, CV-6209, inhibited generation of the active conditioned medium by PAF. Addition of the PAF antagonist only partially suppressed the augmentative effect of the active conditioned medium on DNA synthesis; this is consistent with the fact that, because of the rapid breakdown, no appreciable amount of PAF remained in the conditioned medium of PAF-treated cells. Although mouse bone marrow cells did not respond to PAF unlike guinea pig cells, their DNA synthesis was significantly enhanced by the conditioned medium of PAF-treated guinea pig bone marrow cells. Thus, some newly generated factor(s) distinct from the originally inoculated PAF seemed to modulate the bioactions of PAF on bone marrow cells. An appreciable amount of PAF was produced by calcium ionophore-treated guinea pig bone marrow cells. These findings indicate that PAF synthesized in guinea pig bone marrow cells induces generation in the cells of some factor(s) which affects proliferation or microbicidal activity. Presented at The Third International Conference on Platelet-Activating Factor and Structurally Related Ether Lipids, Tokyo, Japan, May 1989.     

Studying re-opened bugs in open source software

Bug fixing accounts for a large amount of the software maintenance resources. Generally, bugs are reported, fixed, verified and closed. However, in some cases bugs have to be re-opened. Re-opened bugs increase maintenance costs, degrade the overall user-perceived quality of the software and lead to unnecessary rework by busy practitioners. In this paper, we study and predict re-opened bugs through a case study on three large open source projects—namely Eclipse, Apache and OpenOffice. We structure our study along four dimensions: (1) the work habits dimension (e.g., the weekday on which the bug was initially closed), (2) the bug report dimension (e.g., the component in which the bug was found) (3) the bug fix dimension (e.g., the amount of time it took to perform the initial fix) and (4) the team dimension (e.g., the experience of the bug fixer). We build decision trees using the aforementioned factors that aim to predict re-opened bugs. We perform top node analysis to determine which factors are the most important indicators of whether or not a bug will be re-opened. Our study shows that the comment text and last status of the bug when it is initially closed are the most important factors related to whether or not a bug will be re-opened. Using a combination of these dimensions, we can build explainable prediction models that can achieve a precision between 52.1–78.6 % and a recall in the range of 70.5–94.1 % when predicting whether a bug will be re-opened. We find that the factors that best indicate which bugs might be re-opened vary based on the project. The comment text is the most important factor for the Eclipse and OpenOffice projects, while the last status is the most important one for Apache. These factors should be closely examined in order to reduce maintenance cost due to re-opened bugs.     

Efficient Leave-<Emphasis Type="Italic">m</Emphasis>-out Cross-Validation of Support Vector Regression by Generalizing Decremental Algorithm

We propose a computationally efficient method for cross-validation of the Support Vector Regression (SVR) by generalizing the decremental algorithm of SVR. Incremental and decremental algorithm of Support Vector Machines (SVM) ^{2, 8, 9)} efficiently update the trained SVM model when a single data point is added to or removed from the training set. The computational cost of leave-one-out cross-validation can be reduced using the decremental algorithm. However, when we perform leave-m-out cross-validation (m > 1), we have to repeatedly apply the decremental algorithm for each data point. In this paper, we extend the decremental algorithm of SVR^{8, 9)} in such a way that several data points can be removed more efficiently. Experimental results indicate that the proposed approach can reduce the computational cost. In particular, we observed that the number of breakpoints, which is the main computational cost of the involved path-following, were reduced from \({\mathcal O}(m)\) to \({\mathcal O}(\sqrt{m})\).     

Construction of a brain–machine hybrid system to evaluate adaptability of an insect

Insects perform adaptive behavior according to changing environmental conditions using comparatively small brains. Because adaptability is generated through the relationship among brain, body and environment, it is necessary to examine how a brain works under these conditions. In this study, to understand neural processing involved in adaptive behavior, we constructed a brain–machine hybrid system using motor signals related to the steering behavior of the male silkworm moth for controlling a two-wheeled mobile robot. We developed this hybrid system according to the following steps. (1) We selected steering signals corresponding to walking direction that were activated during neck swinging induced by optic flow and pheromone stimuli. (2) To control a robot by neural activity, we implemented a spike-behavior conversion rule such that frequency of the left and right neck motor neurons’ spikes was linearly converted into rotation of the wheels. (3) For electrophysiological multi-unit recordings on a robot, we developed small amplifiers. Using this hybrid system, we could observe the programmed behavioral pattern and orientation toward a pheromone source. Moreover, we compared the orientation behavior of moths and that of the hybrid system at different pheromone stimulus frequencies. From these experiments, we concluded that we could reconstruct silkworm moth behavior on the hybrid system.