Physiologically-based pharmacokinetic (PBPK) models include drug-specific and physiology-specific components. This feature allows simultaneous evaluation of the effects of multiple patient factors on pharmacokinetics and pharmacodynamics of a drug in humans. The last decade observed exponential increase in the use of PBPK to address drug development questions. Today, global regulatory bodies are routinely reviewing PBPK analyses submitted by drug sponsors. Among the US FDA, EMA and Japan's PMDA, discussions are ongoing with regard to recommendations on determining adequacy of a PBPK analysis. In 2016, FDA and EMA published first draft guidance and guideline on format and content of PBPK analyses submitted for review. Confidence of using PBPK varies depending on the predictive performance for an intended use. Predictive performance is generally established in the area of predicting enzyme based drug-drug interaction potential for investigational drug as victims. Under certain conditions, PBPK-simulated interaction magnitude is considered adequate by regulators to replace a dedicated clinical interaction trial. Simulated results have been included in product labels in the US, EU, and Japan. Confidence in using PBPK to predict drug PK in other areas are emerging. It continues to be challenging to predict PK in a specific population (e.g., pediatrics, patients with renal or hepatic impairment) using PBPK.

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The general purpose of synchronous belt drive is the power transmission, and the cam shaft drive on automotive engine is a typical example of such applications. While, also in conveyor belt applications, there are many kinds of field experiences such as coin conveyance and bill, etc. This paper explains about the caterpillar belt applications which are required both performance of power transmission and conveyance.

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The flowout behavior of molten metal (ADC12) through many of a die casting runner has been examined. The flowout behavior of water through the was similar to that of molten metal. Flowout volume through the lower runner was greater than the volume through the upper runner ones, and bubbles appeared in the runner when the unpressurised system (main runner/sub runner=1:1.6) was used. Flowout volumes through the were equal to one another when the pressurised system (main runner/sub runner=1:0.8) was used and the ratio ( area/runner area) was reduced to 0.3. Filling-up time was shortened by using the pressurised system and reducing the ratio (gate area/runner area) to 0.5. The bubbles, which appeared in the runner with the unpressurised system, were not observed in the one with a pressurised system.

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  In die casting, the gas inside the injection sleeve and the mold affect the product quality. For this reason, it is necessary to discharge the gas out of the mold as much as possible, and exhaust

are usually provided for this purpose. However, as product shapes become more complex and the variety of products becomes smaller, the difficulties involved in designing the exhaust of such products and the time required for the design process are increasingly becoming challenging issues. On the other hand, recent design methods based on iterative calculations are difficult to apply to the design of exhaust because the entire mold needs to be calculated. In this study, we developed a system to automatically design the position and width of exhaust that can properly discharge the gas out of the mold without the need for iterative calculations by ranking the best areas of the mold for installing the exhaust based on the filling time of molten metal. Finally, experiments were conducted using actual die castings and the results showed that the proposed exhaust gate shape can reduce the blowhole inside the product well.

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The discovery that a particular pair of satellited chromosomes is concerned in producing the nucleolus in telophase depended an several independent lines of observation. The satellites were first observed by S. Navashin in 1912 as bodies attached to the nucleolus, and were believed to become attached to their respective chromosomes later in the prophase.
The earlier cytologists believed the nucleolus to arise as an independent body in telophase and to pass material an to the chromatin thread in prophase. A definite connection of morphological significance was first observed in polten mother cells of Lathyrus by Latter in 1926, between the nucleolus and the chromatin thread, the latter being constantly attached in leptotene and zygotene stages to a more deeply staining portion of the nucleolus which was called the nucleolar body.
In 1931, from observations of somatic telophase in various plants, Heitz concluded that a particular pair of satellited chromosomes was responsible for producing two nucleoli, or one if they were lying near enough together to touch and fuse.
In 1934, from a reciprocal translocation in maize in which the nucleolar body was broken into two, McClintock concluded that the nucleolar body was situated at a particular locus of the chromosome adjacent to the satellite, and that this body was normally concerned in organizing the nucleolus from the material of the chromosome matrix.
In 1934, essentially the saure relationships were shown for animals by Dearing, through an investigation of the somatic nuclei of Amblystoma. Two subterminal granules an the split telophase chromosome were found to fuse shortly, afterwards growing gradually into a nucleolus from that chromosome, which bears a large satellite at metaphase.
Among subsequent observations, it is found that in the polten mother celis of rice a terminal knob rather than a satellite is attached to the nucleolus, and that this attachment remains while the nucleolus gradually disappears. Primula seclusa and certain strains of Narcissus bulbocodium. var. genuinus near Coimbra also appear to lack satellited chromosomes, yet produce a nucleolus. Similar conditions were found in Liverworts. The presence of a connecting thread is therefore unessential.
A diploid nucleus in plants or animals then usually contains a pair of chromosomes which are mainly concerned in organizing the nucleolus in telophase at a particular locus. This locus is usually subterminal, giving a satellite attached by a thread, which may increase greatly in length as the nucleolus grows.
Various other conditions are derivable from this through translocation, or perhaps in some Gases through mutation. Questions of variation in the size of satellites, or their disappearance, and their relation to particular phenotypic characters require further elucidation.
There appear to be two kinds of satellites, one concerned in the production of a nucleolus and the other not. Why the nucleolar body should be generally subterminal an a chromosome is not clear, nor is the nature of the delicate thread connecting the satellite to the chromosome.

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The Kojima Lake is an artificial lake. The bank was built at the narrowest point of the Kojima Gulf and it separates the sea and the lake. There are 12 watergates and one set of lockgate. These were painted by vinyl paint about 3 years ago. The paint is deteriorated to some extent, and rust was found on the gate surfaces from place to place. These are now protected by sacrificial anodes. There are some problems to be considered in this cathodic protection design. The lockgates are opened 30-40times daily, and several watergates are opened daily for a few hours to adjust the lake water level. Therefore, polarization of will be interrupted quite frequently. The resitivity of lake water is affected by many factors, i.e. season, weather, water depth, duration and frequency of gate opening, leakage rate of the , etc. Zinc anodes are used in the sea and in the lock chamber, and Mg anodes are used in the lake. Protective current density is 40mA/m² and designed potential of the is -900mV referred to S.C.E. Satisfactory results are obtained in the seaside, but minimum protective potential of -770mV referred to S.C.E. is maintained in the lock chamber and in the lake.

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Despite the popularity of RNN, LSTM and GRU, there was little evidence that confirmed their performance.  We tried to investigate to reveal underlying processes and conditions to deal with such of them.  The meanings of multi-layered RNNs might also be possible based on these findings as well.

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Many Tainter- are being used with increased frequencies also in Japan, in order to control the water level of reservoirs. In this type of gate system, the effect of mechanical frictions is much less than in the type of vertical-lift , therefore providing a small hoisting load and a smooth operation of the gate. Though Tainter- have such great advantages, these facilities of the mechanism yield a fear that Tainter- may oscillate owing to some fluid-induced structural load, i.e. the operation of Tainter- may tend to become unstable. In this study, the stability of an idealized Tainter-gate system without damping effects, which is caused by surface waves on the back water of dam, was theoretically analyzed, but the analysis was restricted to the case that the resultant of the hydraulic pressure exerted on the weir plate passes under the trunnion pin. It was concluded as follows : Tainter- fundamentally possess the property of a self-excited oscillation.

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Mixed-Polarity Multiple-Control Toffoli (MPMCT)

are generally used to implement large control logic functions for quantum computation. A logic circuit consisting of MPMCT needs to be mapped to a quantum computing device that invariably has a physical limitation, which means we need to (1) decompose the MPMCT into one- or two-qubit , and then (2) insert SWAP so that all the can be performed on Nearest Neighbor Architectures (NNAs). Up to date, the above two processes have only been studied independently. In this work, we investigate that the total number of in a circuit can be decreased if the above two processes are considered simultaneously as a single step. We developed a method that inserts SWAP while decomposing MPMCT unlike most of the existing methods. Also, we consider the effect on the latter part of a circuit carefully by considering the qubit placement when decomposing an MPMCT gate. Experimental results demonstrate the effectiveness of our method.

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The Six Subtle Dharma

(六妙門 Liumiaomen) is one of Zhiyi’s earlier works. It sets forth the Indeterminate Śamatha-vipaśyanā meditation. It is found in the Taishō Tripiṭaka’s forty-sixth volume. Recently, Professor Toshinori Ochiai discovered a version of the Six Subtle Dharma in the Tripiṭaka kept at Nanatsu-dera. Another version is also found in the Zhaocheng Jin Tripiṭaka. Based on the the Nanatsudera and Zhaocheng Jin texts, in this article I will discuss the following two points. First, I will investigate the transmission lineage of the Six Subtle Dharma . Next, I will argue that the Six Subtle Dharma was written before the Sequential Meditative (次第禅門 Cidi Chanmen) and not the other way around as thought earlier. Hence, the order in which the texts discuss the “six subtle dharma ” meditation is as follows: Six Subtle Dharma , sequential Meditative , Sequence of Dharmadhātu (法界次第 Fajie Cidi) and Profound Meaning of the Lotus Sūtra (法華玄義 Fahua Xuanyi).

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A method of designing compact multiple-input combinational logic circuits is proposed. We show that i) fundamental logic can be constructed by a small number of collision-based fusion , ii) multiple-input logic are constructed in a systematic manner, iii) the number of transistors in specific logic constructed by the proposed method is significantly smaller than that of conventional logic .

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  Water model experiments were made on an L-shaped gating system provided with multiple . The loss coefficients at the basin, sprue, sprue base and were calculated from the measurements of the flow rates at the and the pressures at the sprue and the runner. The loss coefficients are practically independent of the gating ratio and the feeding head. The loss coefficients at the , except the gate adjoining to the runner extension, increase with the number of the attached to the same runner. The calculated values of the loss coefficients at the sprue base and those at the are somewhat larger than those expected from the hydrodynamic data in the literature.

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Integrating basic research and technology into business is a critical factor in corporate competitive strategy. It has been proposed to describe problems in the research and development of companies, and the “Boost Gate (hereafter BG)” method as a method to overcome them. It is suggested that the use of this method leads to invigorated fundamental research activities within corporate R&D. Existing research on BG has provided certain details on the type of advice provided at each gate. Yet, these details have not provided methods for handling promising topics that still did not meet decision criteria, including whether to revert these topics or clear them to the next gate after advice is provided. Further, there are limited cases available for reference wherein BG has been implemented. This paper outlines the advising method for topics that do not meet a

decision criteria in BG. It also provides a reference for leveraging BG in corporate R&D by presenting an actual implementation case of that method.

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In this paper, I examine the doctrine of the five

of mindfulness and the five of virtue in Vasubandhu’s Jingtu lun 浄土論 from the standpoint of syntax.

The doctrine of the five

of mindfulness consists of (A) interrogative sentences beginning with rúhé 如何, (B) sentences answering the interrogations, and (C) sentences stating the reasoning behind (B) ending with gù 故.

Further, the five

of virtue consists of (A’) opening sentences beginning by stating which gate is being explained, using 入/出第～門者, (B’) sentences which correspond to (B) beginning with the character yǐ 以, (C’) sentences finishing with gù 故 giving the reasoning which corresponds to (C), (D’) sentences that reveal the contents of the five of virtue, and (E’) concluding remarks which begin by stating each gate using 是名入/出第～門.

From this, when examining one sentence explaining one of the

it is possible to cross reference it with another section written in the same syntax. This paper uses this method to understand the connection between the five of mindfulness and the five of virtue in Vasubandhu’s Jingtu lun.

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At the FSE conference of ToSC 2018, Kranz et al. presented their results on shortest linear programs for the linear layers of several well known block ciphers in literature. Shortest linear programs are essentially the minimum number of 2-input xor

required to completely describe a linear system of equations. In the above paper the authors showed that the commonly used metrics like d-xor/s-xor count that are used to judge the “lightweightedness” do not represent the minimum number of xor required to describe a given MDS matrix. In fact they used heuristic based algorithms of Boyar-Peralta and Paar to find implementations of MDS matrices with even fewer xor than was previously known. They proved that the AES mixcolumn matrix can be implemented with as little as 97 xor . In this paper we show that the values reported in the above paper are not optimal. By suitably including random bits in the instances of the above algorithms we can achieve implementations of almost all matrices with lesser number of than were reported in the above paper. As a result we report an implementation of the AES mixcolumn matrix that uses only 95 xor . In FSE conference of ToSC 2019, Li et al. had tweaked the Boyar-Peralta algorithm to get low depth implementations of many matrices. We show that by introducing randomness in the tweaked algorithm, it is again possible to get low depth implementations with lesser number of than the above paper. As a result, we report a depth implementation of the AES mixcolumn matrix that uses only 103 xor , which is 2 less than the previous implementation. In the second part of the paper, we observe that most standard cell libraries contain both 2 and 3-input xor , with the silicon area of the 3-input xor gate being smaller than the sum of the areas of two 2-input xor . Hence when linear circuits are synthesized by logic compilers (with specific instructions to optimize for area), most of them would return a solution circuit containing both 2 and 3-input xor . Thus from a practical point of view, reducing circuit size in presence of these is no longer equivalent to solving the shortest linear program. In this paper we show that by adopting a graph based heuristic it is possible to convert a circuit constructed with 2-input xor to another functionally equivalent circuit that utilizes both 2 and 3-input xor and occupies less hardware area. As a result we obtain more lightweight implementations of all the matrices listed in the ToSC paper.

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