Joint Decision-Making Model Based on Consensus Modeling Technology for the Prediction of Drug-Induced Liver Injury

Drug-induced liver injury (DILI) is the major cause of clinical trial failure and postmarketing withdrawals of approved drugs. It is very expensive and time-consuming to evaluate hepatotoxicity using animal or cell-based experiments in the early stage of drug development. In this study, an in silico model based on the joint decision-making strategy was developed for DILI assessment using a relatively large dataset of 2608 compounds. Five consensus models were developed with PaDEL descriptors and PubChem, Substructure, Estate, and Klekota–Roth fingerprints, respectively. Submodels for each consensus model were obtained through joint optimization. The parameters and features of each submodel were optimized jointly based on the hybrid quantum particle swarm optimization (HQPSO) algorithm. The application domain (AD) based on the frequency-weighted and distance (FWD)-based method and Tanimoto similarity index showed the wide AD of the qualified consensus models. A joint decision-making model was integrated by the qualified consensus models, and the overwhelming majority principle was used to improve the performance of consensus models. The application scope narrowing caused by the overwhelming majority principle was successfully solved by joint decision-making. The proposed model successfully predicted 99.2% of the compounds in the test set, with an accuracy of 80.0%, a sensitivity of 83.9, and a specificity of 73.3%. For an external validation set containing 390 compounds collected from DILIrank, 98.2% of the compounds were successfully predicted with an accuracy of 79.9%, a sensitivity of 97.1%, and a specificity of 66.0%. Furthermore, 25 privileged substructures responsible for DILI were identified from Substructure, PubChem, and Klekota–Roth fingerprints. These privileged substructures can be regarded as structural alerts in hepatotoxicity evaluation. Compared with the main published studies, our method exhibits certain advantage in data size, transparency, and standardization of the modeling process and accuracy and credibility of prediction results. It is a promising tool for virtual screening in the early stage of drug development.

Introduction

The central puzzle of the book is introduced: Why is there so much consensus among shareholders of large firms? Although trading on the market forges agreement between shareholders about the firms’ objectives, residual yet substantial disagreement should persist because of market failures. To resolve the puzzle, a vision of the political economy of the (publicly traded) firm is outlined, showing 1) how the upstream operation of a decentralized market mechanism makes collective decision-making in the firm easier and more stable; and 2) why the democratic (majority) principle is likely to promote economic efficiency as a politically stable choice. Yet more is needed: a vision of the social economics of shareholders showing how collective decision-making shapes individual preferences in a way that promotes the alignment of shareholders. These two visions are laid out in the two parts of the book.

The Dual Nature of Law

The argument of this chapter is that the dual-nature thesis is not only capable of solving the problem of legal positivism but also addresses all fundamental questions of law. Examples are the relation between deliberative democracy and democracy qua decision-making procedure along the lines of the majority principle, the connection between human rights as moral rights and constitutional rights as positive rights, the relation between constitutional review qua ideal representation of the people and parliamentary legislation, the commitment of legal argumentation to both authoritative and non-authoritative reasons, and the distinction between rules as expressing a real ‘ought’ and principles as expressing its ideal counterpart. All of this underscores the point that the dual nature of law is the single most essential feature of law.

A discrete-continuous stochastic model functioning of analysis system, generalization and implementation of experience in the use of troops (armed forces)

In article presented theoretic generalization practical efficiency issues training and deployment of troops (armed forces) by improving the analysis system, generalization and implementation of combat experience (ASGIE) and an actual scientific problem was solved in a new way, consisting in the improvement of the scientific and methodological apparatus of its functioning. Performed analysis mathematical models for descriptions and assessment functioning system of training and use of troops (armed forces). In the same time, the results of researches in exercises and other activities of operational, combat training and daily activities of troops (armed forces) showed the absence of effective mathematical models for the functioning of ASGIE of troops (armed forces). The constituents for each of the three performance indicators have been substantiated and determined, which reproduce the corresponding reactions of the ASGIE to obtain a generalized experience. The connection of these constituents with the requirements for the mathematical model of the reaction of the ASGIE is shown. A discrete-continuous stochastic model of the ASGIE reaction has been developed to study the effectiveness of a promising ASGIE for various options for its implementation. A system of Kolmogorov-Chapman differential equations of the first order has been formed, the solution of which gives the opportunity to get the value of performance indicators ASGIE. Calculations performed for ASGI which includes the governing bodies of three military units and three OC with decision-making on the generalization of experience for the majority principle "2 with 3" show: acceptable values of the performance indicator "Experience is generalized" are achieved when the values of the probability of identifying experience and the probability of successful generalization of experience by the management body are greater than 0.9; with the values of the probability of experience identification and the probability of successful generalization of experience by the governing bodies in the range from 0.4 to 0.7 with a probability of not less than 0.7, it will be necessary to continue to accumulate generalized experience in order to make a decision on its dissemination; accordingly, a value in the range from 0.2 to 0.6 is unacceptable for organizing the process of generalizing experience for the developed ASGI.

Indoor Floor Localization Based on Multi-Intelligent Sensors

With the continuous expansion of the market of indoor localization, the requirements of indoor localization technology are becoming higher and higher. Existing indoor floor localization (IFL) systems based on Wi-Fi signal and barometer data are susceptible to external environment changes, resulting in large errors. A method for indoor floor localization using multiple intelligent sensors (MIS-IFL) is proposed to decrease the localization errors, which consists of a fingerprint database construction phase and a floor localization phase. In the fingerprint database construction phase, data acquisition is performed using magnetometer sensor, accelerator sensor and gyro sensor in the smartphone. In the floor localization phase, an active pattern recognition is performed through the collaborative work of multiple intelligent sensors and machine learning classifiers. Then floor localization is performed using magnetic data mapping, Euclidean closest approximation and majority principle. Finally, the inter-floor detection link based on machine learning is added to improve the overall localization accuracy of MIS-IFL. The experimental results show that the performance of the proposed method is superior to the existing IFL.

Democratic majority principle in trouble?

Due to a lack of religious or metaphysical orientation in modern Western societies, interpersonal conflicts of interest and value are solved under the premise of individuals acting rationally through the interaction on a free market and the formation of political majorities gaining legislative power. However, the legitimacy of this approach becomes increasingly questionable when it comes to sustainability conflicts. In view of this, Hans Jonas considered the possibility of the need to suspend democratic institutions in favor of a benevolent tyrant to avert a potential catastrophe. Since any form of centralism comes with its own problems of legitimacy, utilizing the more modest orientation claims of prudence ethics is a more promising alternative in deliberations on the justifiability of an occasional suspension of the majority principle without exposing a society to the dangers of domineering arbitrariness.

Gli hussiti come (mancata) minoranza conciliare al Concilio di Basilea (1431–1433)

In 1433 the hussite delegation in Basle wanted to discuss the Four Articles according to the pacts of Eger (the “judge of Eger”), i.e. primarily according to the Bible. The delegates insisted on persuading the other party or on being persuaded by it; they weren’t willing to become a conciliar minority because the decision-making processes were based on the majority-principle. Furthermore, the Council offered a different “judge”: It was the Council itself, because the infallible Church beheld the “monopoly” of the Bible exegesis and transmitted this monopoly to the Synod. In this way it became less relevant to discuss the specific topics of the Four Articles. The Hussites, however, remained outside this doctrine, which was fundamental for the legitimacy of the conciliar decision-making process: they didn’t recognize this new judge and didn’t subdue to him.

Signal correction for combinational automation devices on the basis of Boolean complement with control of calculations by parity

Simpler than known structure of the system with error correction in calculations is proposed based on duplication and triplication of blocks with majority principle of choosing the values of signals. It is advisable to use the new fault-tolerant structure for automation devices with combinational logic. In fault-tolerant structure synthesis, the parity method is used to establish the fact of a fault in the main logic unit and the logical complement method is used determine incorrectly calculated output functions and to generate signals for their correction. The method also allows to adjust the values of incorrectly calculated functions. Structural diagram and description of error correction system are given. The synthesis algorithm of control equipment is described with minimization of the technical implementation complexity. The experiment results with control combinational circuits are given, confirming the high efficiency of proposed system structure with error correction.

Constitutional Uncertainties

The Calculus of Consent by Buchanan and Tullock was the first book to apply the contract method to questions of public choice, particularly in respect of voting, in the modern era. Their contractual construction imagines individuals in an original position of a laissez-faire economy, where the individuals have to determine rules for the making of collective choices in respect of the reduction of economic externalities and the provision of public goods. Those individuals calculate the costs and benefits of different decision rules. Faced with proposals with which they disagree, individuals would prefer a high threshold of agreement; faced with proposals with which they agree, individuals would prefer a low threshold of agreement. The constitutional question such individuals confront is to determine a general decision rule when they are uncertain about the future stream of choices the members of their community will face. Buchanan and Tullock are defended against the criticism that their original position lacks justification and that it presupposes a requirement of unanimity to secure change. However, they are less convincing in their attack on the simple majority principle, and in their attempt to show that supermajority decision-making does not give too much power to minorities. Indeed, sometimes the supermajority devices they support should be used to protect minorities, as shown in the literature on consociational democracy.