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This article discusses the right to assisted suicide, a right not derived from anything explicit or implied in any textual provision of the Constitution. It is a right derived from the two underlying political philosophies, which form the basis of the entire U.S. Constitutional enterprise: John Locke's Social Contract and Civic Republicanism. In Part I, this article discusses Glucksberg's fundamental rights analysis. So much has been written about this case that this article will limit comments to briefly adding thoughts as to why, given the combination of the Court's motivation, both institutional and pragmatic, in approaching this case, and its methodology for analyzing fundamental rights, a nine to zero decision was fairly predictable, even in this difficult, emotionally compelling case. Part II gives more consideration to the equal protection claim. Those entering the debate in Vacco v. Quill regarding whether there is an equivalence between terminating life support (which the law permits) and assisted suicide (which the law forbids), have done so in a rather conclusory fashion, whether contending for" or against" equivalence. Many entering the debate also have failed to explicitly question whether, even if what we condone in end-of-life care cannot be morally distinguished from assisted suicide, there may be meaningful distinctions in policy of which the law may properly take into account. A detailed equal protection analysis of legally accepted medical practices in end-of-life care-pulling the plug, refusing treatment, the principle of double effect, and terminal sedation is, therefore, appropriate. In Part III, this article discusses the Social Contract theory and Civil Republicanism. I explain why the combination of these political philosophies underlying the Constitution provide people like my father, both past the age of Social Security retirement and incapable of ever again participating in the political process, with a right to end their lives.

When America attacked Iraq in 2002, it was the first preemptive war in the history of our nation. While there is daily debate over the wisdom and consequences of that action, the question whether the federal government even possessed the power under the Constitution to wage preemptive war does not seem to have been raised. Although the legal literature abounds with discussion about whether the President may authorize significant military operations without the explicit authorization of Congress, the author could not find a single work written in legal cases or commentary about preemptive war. This article considers this heretofore unanswered question of whether the federal government possesses the power to engage in preemptory war. Looking at a variety of sources, including America's use of military force throughout its history, the framer's view of war, and the political philosophy and religious views of the framers, the author concludes that such power is beyond that given the federal government in the Constitution. Thus, even were both the President and Congress to concur in such a war, with Congress making a formal declaration of war, the action would be unconstitutional. The article also explains why the Political Question Doctrine does not bar judicial review of whether or not a proposed use of military force is preemptive.

Includes bibliographical references (p. 163-210) and index. ; Cultural arguments that assisted suicide is always wrong -- Religious arguments for maintaining that suicide is morally "wrong" -- Utilitarian arguments against suicide -- The slippery slope phenomenon -- My path turns: looking at autonomy and moral claims to the right to assisted suicide -- Act utilitarianism as a moral basis for justifying assisted suicide -- The moral claim justifying physician-assisted suicide with the combination of autonomy and mercy -- Law and assisted suicide -- The question of whether legislatures should or should not legalize physician-assisted suicide. ; Mode of access: Internet.

This work was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 812777 ; Differences in the expression patterns of genes have been used to measure the effects of non-stress or stress conditions in poultry species. However, the list of genes identified can be extensive and they might be related to several biological systems. Therefore, the aim of this study was to identify a small set of genes closely associated with stress in a poultry animal model, the chicken (Gallus gallus), by reusing and combining data previously published together with bioinformatic analysis and Bayesian networks in a multi-step approach. Two datasets were collected from publicly available repositories and pre-processed. Bioinformatics analyses were performed to identify genes common to both datasets that showed differential expression patterns between non-stress and stress conditions. Bayesian networks were learnt using a Simulated Annealing algorithm implemented in the software Banjo. The structure of the Bayesian network consisted of 16 out of 19 genes together with the stress condition. Network structure showed CARD19 directly connected to the stress condition plus highlighted CYGB, BRAT1, and EPN3 as relevant, suggesting these genes could play a role in stress. The biological functionality of these genes is related to damage, apoptosis, and oxygen provision, and they could potentially be further explored as biomarkers of stress. ; Publisher PDF ; Peer reviewed

D.S.P. and D.J.F. thank the EPSRC for funding via Prosperity Partnership EP/S035990/1. D.S.P. and D.J.F. thank the ARCHIE-WeSt High-Performance Computing Centre (www.archie-west.ac.uk) for computational resources. The UCL authors thank Prof. Keith Refson for guidance with the phonon calculations, which used the ARCHER U.K. National Supercomputing Service (http://www.archer.ac.uk) as part of the U.K. HEC Materials Chemistry Consortium, which is funded by the EPSRC (EP/L000202, EP/R029431). R.G. was funded by MagnaPharm, a project funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 736899. ; We demonstrate that physics-based calculations of intrinsic aqueous solubility can rival cheminformatics-based machine learning predictions. A proof-of-concept was developed for a physics-based approach via a sublimation thermodynamic cycle, building upon previous work that relied upon several thermodynamic approximations, notably the 2RT approximation, and limited conformational sampling. Here, we apply improvements to our sublimation free-energy model with the use of crystal phonon mode calculations to capture the contributions of the vibrational modes of the crystal. Including these improvements with lattice energies computed using the model-potential-based Ψmol method leads to accurate estimates of sublimation free energy. Combining these with hydration free energies obtained from either molecular dynamics free-energy perturbation simulations or density functional theory calculations, solubilities comparable to both experiment and informatics predictions are obtained. The application to coronene, succinic acid, and the pharmaceutical desloratadine shows how the methods must be adapted for the adoption of different conformations in different phases. The approach has the flexibility to extend to applications that cannot be covered by informatics methods. ; Publisher PDF ; Peer reviewed

The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug discovery programs. A probabilistic method, the ParzenRosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D-1-R/D-2-R/5-HT2A-R/H-3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs. ; European Union (EU) European Cooperation in Science and Technology (COST) Ministry of the Republic of Serbia Marie Sklodowska-Curie action FP7-MC-ITN

This work was supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 812777. We also greatly appreciate funding from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) grants #2018-01074 and #2017-00946 to CG-B. FP appreciates funding from São Paulo Research Foundation (FAPESP, Brazil) projects #2016/20440-3 and #2018/13600-0. ; Background: Relationships among genetic or epigenetic features can be explored by learning probabilistic networks and unravelling the dependencies among a set of given genetic/epigenetic features. Bayesian networks (BNs) consist of nodes that represent the variables and arcs that represent the probabilistic relationships between the variables. However, practical guidance on how to make choices among the wide array of possibilities in Bayesian network analysis is limited. Our study aimed to apply a BN approach, while clearly laying out our analysis choices as an example for future researchers, in order to provide further insights into the relationships among epigenetic features and a stressful condition in chickens (Gallus gallus). Results: Chickens raised under control conditions (n = 22) and chickens exposed to a social isolation protocol (n = 24) were used to identify differentially methylated regions (DMRs). A total of 60 DMRs were selected by a threshold, after bioinformatic pre-processing and analysis. The treatment was included as a binary variable (control = 0; stress = 1). Thereafter, a BN approach was applied: initially, a pre-filtering test was used for identifying pairs of features that must not be included in the process of learning the structure of the network; then, the average probability values for each arc of being part of the network were calculated; and finally, the arcs that were part of the consensus network were selected. The structure of the BN consisted of 47 out of 61 features (60 DMRs and the stressful condition), displaying 43 functional ...