OBDDs of a Monotone Function and Its Prime Implicants

Coudert made a breakthrough in the two-level logic minimization problem with Ordered Binary Decision Diagrams (OBDDs for short) recently [3]. This paper discusses the relationship between the two OBDDs of a monotone function and its prime implicant set to clarify the complexity of this practically efficient method. We show that there exists a monotone function which has an O(n) size sum-of-products but cannot be represented by a polynomial size OBDD. In other words, we cannot obtain the OBDD of the prime implicant set of a monotone function in an output-size sensitive manner once we have constructed the OBDD of that function as in [3], in the worst case. A positive result is also given for a meaningful class of matroid functions. Received April 1997, and in revised form December 1997, and in final form February 1998.     

Bile Acid–Drug Interaction via Organic Anion-Transporting Polypeptide 4C1 Is a Potential Mechanism of Altered Pharmacokinetics of Renally Excreted Drugs

Patients with liver diseases not only experience the adverse effects of liver-metabolized drugs, but also the unexpected adverse effects of renally excreted drugs. Bile acids alter the expression of renal drug transporters, however, the direct effects of bile acids on drug transport remain unknown. Renal drug transporter organic anion-transporting polypeptide 4C1 (OATP4C1) was reported to be inhibited by chenodeoxycholic acid. Therefore, we predicted that the inhibition of OATP4C1-mediated transport by bile acids might be a potential mechanism for the altered pharmacokinetics of renally excreted drugs. We screened 45 types of bile acids and calculated the IC₅₀, K_i values, and bile acid–drug interaction (BDI) indices of bile acids whose inhibitory effect on OATP4C1 was >50%. From the screening results, lithocholic acid (LCA), glycine-conjugated lithocholic acid (GLCA), and taurine-conjugated lithocholic acid (TLCA) were newly identified as inhibitors of OATP4C1. Since the BDI index of LCA was 0.278, LCA is likely to inhibit OATP4C1-mediated transport in clinical settings. Our findings suggest that dose adjustment of renally excreted drugs may be required in patients with renal failure as well as in patients with hepatic failure. We believe that our findings provide essential information for drug development and safe drug treatment in clinics.     

Optimal Digital Controller Design for a Servo Motor Taking Account of Intersample Behavior

A continuous‐time plant with a discretized continuous‐time controller does not yield stability if the sampling rate is lower than some certain level. Thus far, high‐performance electronic control has made use of expensive hardware needed to implement discretized continuous‐time controllers; low‐cost hardware generally does not have a sufficiently high sampling rate. This technical note presents results comparing performance indexes with and without intersample behavior, and provides some answers to the question of how a low‐specification device can control a plant effectively. We consider a machine simulating wafer handling robots, which is an electromechanical system driven by a direct drive motor, at a semiconductor factory. We illustrate the controller design for the robot with and without intersample behavior, and present simulations and experimental results using these controllers. Taking intersample behavior into account proves to be effective in improving control performance and makes it possible to choose a relatively long sampling period. Controller design in terms of the performance index with intersample behavior makes it possible to deal with situations in which a sufficiently short sampling period may not be employed, and freedom of controller design may be widened, especially regarding the choice of the sampling period.     

Mouse Gastric Epithelial Cells Resist CagA Delivery by the Helicobacter pylori Type IV Secretion System

The initial step in bacterial infection is adherence of the bacterium to the target cell surface. Helicobacter pylori exploits the interaction of bacterial adhesin protein HopQ with human epithelial CEACAMs (CEACAM1, 5, and 6) to stably adhere to gastric epithelial cells, which is necessary for delivery of the H. pylori CagA oncoprotein into the epithelial cells via a type IV secretion system. In contrast to human CEACAMs, however, HopQ does not interact with Ceacam1 (mouse CEACAM1) in vitro or in CHO cells ectopically expressing Ceacam1. Since the mouse genome lacks Ceacam5 and Ceacam6, no significant HopQ–Ceacam interaction may occur in mouse gastric epithelial cells. Here, we found that the mouse stomach has a much lower expression level of Ceacam1 than the expression level of CEACAM1 in the human stomach. Consistently, mouse gastric epithelial cells resist CagA delivery by cagA-positive H. pylori, and the delivery is restored by ectopic expression of human CEACAM1 or CEACAM5 in mouse gastric epithelial cells. Thus, despite the fact that mice are routinely used for H. pylori infection studies, a low expression level of Ceacam1 in the mouse stomach together with the loss or greatly reduced interaction of HopQ with Ceacams make the mouse an inappropriate model for studying the role of H. pylori-delivered CagA in gastric pathogenesis, including the development of gastric cancer.     

Effects of EDTA saturated with Ca2+ (Ca-EDTA) on pig,bovine and mouse oocytes at the germinal vesicle stage during maturation culture and the involvement of chelation of Zn2+ in pronuclear formation induction by Ca-EDTA

EDTA saturated with Ca(2+), Fe(3+) or Cu(2+) can induce parthenogenetic activation of pig oocytes at the germinal vesicle stage, whereas EDTA saturated with Zn(2+), which is unable to chelate Zn(2+), does not, indicating that chelation of Zn(2+) with EDTA saturated with Ca(2+) (Ca-EDTA) in maturing pig oocytes plays a pivotal role in the induction of parthenogenetic activation of oocytes. In the present study, the involvement of Zn(2+) chelation in the induction of parthenogenetic activation of pig oocytes at the germinal vesicle stage was confirmed first by examining the effects of concomitant addition of Zn(2+), Cu(2+) or Ni(2+) at various concentrations together with 1 mmol Ca-EDTA l(-1) to the maturation medium. The titration experiments revealed that the pronuclear formation induced by 1 mmol Ca-EDTA l(-1) was completely inhibited by the addition of > 30 micromol Zn(2+) l(-1) to the medium, but not by the addition of Cu(2+) and Ni(2+) at any concentration examined. Second, bovine and mouse oocytes at the germinal vesicle stage were cultured in medium with or without 1 mmol Ca-EDTA l(-1) for 48 h to examine the effects of Ca-EDTA treatment on these oocytes during maturation culture. Most (70-86%) of the bovine oocytes that underwent germinal vesicle breakdown matured to the MII stage via the MI phase, regardless of whether Ca-EDTA was present for the first 24 h of culture. However, 61% of oocytes that had been cultured with Ca-EDTA for 48 h formed a pronucleus without a second polar body, whereas oocytes cultured in the absence of Ca-EDTA were not observed to form a pronucleus at any time during culture. However, even when mouse oocytes at the germinal vesicle stage were cultured for up to 48 h in maturation medium containing Ca-EDTA, pronuclear formation was not observed. Finally, when bovine oocytes that had been cultured with 1 mmol Ca-EDTA l(-1) for 48 h from the germinal vesicle stage were cultured further in medium without Ca-EDTA that was supplemented with 5% fetal calf serum, only 26% of the oocytes developed to the cleaved stage, and none could develop further.     

Alleviation of the two-cell block of ICR mouse embryos by polyaminocarboxylate metal chelators

The present study was undertaken to examine the effects of various transition metal ion chelators, both polyaminocarboxylates (including nitrilotriacetate (NTA), ethylenediaminediacetate (EDDA), ethyleneglycolbistetraacetate (EGTA), ethylenediaminetetraacetate (EDTA) and diethylenetriaminepentaacetate (DTPA)) and non-polyaminocarboxylates (dipicolinic acid and deferoxamine), on the development in vitro of one-cell ICR strain mouse embryos to the four-cell and blastocyst stages. The order of stability constants of polyaminocarboxylates for transition metal ions such as zinc, copper and iron is as follows: NTA < or = EDDA < EGTA < EDTA < DTPA. Addition of 10 or 100 micromol polyaminocarboxylates x l(-1) to the medium significantly enhanced the development of most one-cell embryos (66-88%) beyond the two-cell stage compared with that (< 25%) in medium without polyaminocarboxylates. Although EDDA, EDTA and DTPA at 10 micromol x l(-1) induced the development of most one-cell embryos to the four-cell stage and beyond, a higher concentration (100 micromol x l(-1)) of NTA and EGTA was required to obtain a similar result. Therefore, the ability of polyaminocarboxylates to overcome the two-cell block is not correlated with their potency to chelate transition metal ions. In contrast, the non-polyaminocarboxylates dipicolinic acid and deferoxamine, at 10 and 100 micromol x l(-1), did not have the same effect. Taken together, the results indicate that the ability of polyaminocarboxylates to overcome the two-cell block in embryo development is due to some common feature or features other than the ability to chelate transition metal ions.     

Space charge behavior in polymer film based on increment of capacitance under AC high field

Polymer materials have excellent dielectric and insulation properties; however, those properties in AC high field region have not been known well. Recently we established an evaluation method of high‐field AC dissipation current waveform of polymer materials 1 . AC dissipation current waveforms of polyethylene and polypropylene films show nonlinear distortion in AC high‐field region. This nonlinearity was thought to be related to the behavior of AC space charge formation in the sample near electrodes. The properties of space charge formed under AC high field at power frequency seem to differ from those formed under DC high field. The measurement of AC space charge distribution is not so easy due to the resolution limit of the space charge measurement. We studied the dielectric properties of biaxially oriented polypropylene (BOPP) film under AC high field up to 120 °C. It was found that tan δ, AC dissipation current (Ixr), and unbalanced component of capacitive current (ΔIxc) increased when the temperature became higher. In particular, ΔIxc increased above some threshold field and was considered to be due to the AC space charge formation. This AC space charge layer near electrode is thought to be formed due to carrier injection under AC high‐field application. Usually, the carrier mobility becomes smaller on lowering the temperature. Most of the carriers injected from the electrode are trapped near the electrode in the sample film. But in the high‐temperature region, the carrier mobility becomes larger and the carrier injection starts to increase from lower field. Many more carriers are injected from the electrode. It is thought that some of the injected carriers are trapped inside the sample film; the others go through the sample to the opposite side. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 141(2): 8–16, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10018