Unusual Features of the SARS-CoV-2 Genome Suggesting Sophisticated Laboratory Modification as a Biological Robot

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to deaths worldwide and decimation of the global economy. Despite its tremendous impact, the origin of SARS-CoV-2 has remained mysterious and controversial. The natural origin theory, although widely accepted, lacks substantial support. The alternative theory that the virus may have come from a research laboratory is, however, censored on peer-reviewed scientific journals. Nonetheless, SARS-CoV-2 shows biological characteristics that are inconsistent with a naturally occurring, zoonotic virus. In this report, the authors describe the genomic, structural, medical, and literature evidence, which, when considered together, strongly contradicts the natural origin theory. The evidence shows that SARS-CoV2 should be a laboratory product created by using bat coronaviruses ZC45 and/or ZXC21 as a template and/or backbone. Building upon the evidence, the authors further postulate a synthetic route for SARS-CoV-2, demonstrating that the lab-creation of this coronavirus is convenient and can be accomplished in approximately six months.

Mutability and Relationality: Towards an African Four-Dimensionalist Pan-Psychism

This article challenges a certain Theist conception of God as immutable. I argue that the idea that God is immutable can be challenged on the grounds of its metaphysical groundwork. More precisely, I contend that the idea that God is immutable entails endurantism, which I demonstrate to be mistaken. This view cannot be right because it potentially involves three absurd implications: (a) a violation of the principle of the Indiscernibility of Identicals (b) the idea that God becomes a different God with any change that occurs (c) the view that only the present is real and there is no future and past. As these solutions are absurd, the endurantist view ought to be abandoned. I then suggest an alternative theory that does not meet the same problems, which I call African four-dimensionalist Pan-Psychism. This theory I advance maintains that God is the sum of His spatial and temporal parts, is mutable and has relational properties (e.g., He changes with the occurrence of evil or good in the world). I uphold that this view does not have the absurd implications of its competitors.

The damage-independent evolution of ageing by selective destruction

Ageing is currently believed to reflect the accumulation of molecular damage due to energetic costs of maintenance, as proposed in disposable soma theory (DST). Here we have used agent-based modelling to describe an alternative theory by which ageing could undergo positive selection independent of energetic costs. We suggest that the selective advantage of fast-growing mutants might necessitate a mechanism of counterselection we name selective destruction, which removes the faster growing cells from the tissue, preventing the threat of morbidity and mortality they pose. As a result, the survival advantage would shift to the slower cells, allowing them to spread, inducing ageing in the form of a metabolic slowdown. Selective destruction could therefore provide a proximal cause of ageing that is both consistent with the gene expression hallmarks of ageing, and independent of accumulating damage. If true, negligible senescence would acquire a new meaning of increased basal mortality.

The activity of the intrinsically water-soluble enzyme ADAMTS13 correlates with the membrane state when bound to a phospholipid bilayer

Membrane-associated enzymes have been found to behave differently qualitatively and quantitatively in terms of activity. These findings were highly debated in the 1970s and many general correlations and reaction specific models have been proposed, reviewed, and discarded. However, new biological applications brought up the need for clarification and elucidation. To address literature shortcomings, we chose the intrinsically water-soluble enzyme a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) and large unilamellar vesicles with a relative broad phase transition. We here present activity measurements of ADAMTS13 in the freely dissolved state and the membrane associated state for phosphocholine lipids with different acyl-chain lengths (13:0, 14:0 and 15:0) and thus main phase transition temperatures. While the freely dissolved enzyme shows a simple Arrhenius behavior, the activity of membrane associated ADAMTS13 in addition shows a peak. This peak temperature correlates with the main phase transition temperature of the used lipids. These findings support an alternative theory of catalysis. This theory predicts a correlation of the membrane associated activity and the heat capacity, as both are susceptibilities of the same surface Gibb’s free energy, since the enzyme is attached to the membrane.

The Political Theory of Thomas More’s Epigrammata

This essay argues that More’s Epigrammata contains a coherent political theory that is inspired by ancient Roman republicanism. More defines “liberty” as the people’s willing obedience to virtuous leaders who rule for the common good, and he claims that popular opinion is the source of legitimacy rather than divine sanction. In doing so, More critiques the Tudor regime and presents an alternative theory of kingship based on his understanding of liberty. However, More also criticizes hereditary monarchy as such and explicitly prefers a republican regime of elected men who share authority among equal peers. This republican regime more effectively promotes the common good, but it depends upon virtue in the rulers and in the citizens. More’s satirical epigrams on virtue and vice are part of his political teaching insofar as they establish his conception of citizen virtue, which supports his republicanism.

Theoretical Analysis of Principal Components in an Umbrella Model of Intraspecific Evolution

Principal component analysis (PCA) is one of the most frequently-used approach to describe population structure from multilocus genotype data. Regarding geographic range expansions of modern humans, interpretations of PCA have, however, been questioned, as there is uncertainty about the wave-like patterns that have been observed in principal components. It has indeed been argued that wave-like patterns are mathematical artifacts that arise generally when PCA is applied to data in which genetic differentiation increases with geographic distance. Here, we present an alternative theory for the observation of wave-like patterns in PCA. We study a coalescent model -- the umbrella model -- for the diffusion of genetic variants. The model is based on a hierarchy of splits from an ancestral population without any particular geographical structure. In the umbrella model, splits occur almost continuously in time, giving birth to small daughter populations at a regular pace. Our results provide detailed mathematical descriptions of eigenvalues and eigenvectors for the PCA of sampled genomic sequences under the model. Removing variants uniquely represented in the sample, the PCA eigenvectors are defined as cosine functions of increasing periodicity, reproducing wave-like patterns observed in equilibrium isolation-by-distance models. Including rare variants in the analysis, the eigenvectors corresponding to the largest eigenvalues exhibit complex wave shapes. The accuracy of our predictions is further investigated with coalescent simulations. Our analysis supports the hypothesis that highly structured wave-like patterns could arise from genetic drift only, and may not always be artificial outcomes of spatially structured data. Genomic data related to the peopling of the Americas are reanalyzed in the light of our new theory.

Two Theories of Natural Justice in Plato’s Gorgias

In Plato’s Gorgias 482c4–484c3, Callicles advances a concept of natural justice: the laws of the polis must agree with nature, that is, human nature. Since human nature is characterised by its desire to get a greater share (pleon echein), nature itself makes it legitimate that stronger human beings get a greater share than weaker ones. Socrates objects: Callicles’ theoretical approach to civic life poses a threat to the polis’ community, its citizens, and to the friendship amongst its citizens. However, Socrates accepts Callicles’ premise, that the laws of the polis must agree with nature (again, human nature). Still, he disagrees with Callicles about the nature of human nature and proposes an alternative theory of human nature, eventually leading to his alternative concept of natural justice. The article explains the arguments underpinning these two concepts of natural justice, including the conflicting understandings of human nature.

The Role of Health Profession Regulation in Health Services Improvement

<p>This research investigates the role of health practitioner regulation in health service improvement. Over the last 25 years, service improvement has included management reforms, quality and redesign programmes, multidisciplinary teamwork, the integration of clinical information systems, and new roles for health professionals. Yet despite sustained effort, improvements tend to be localised rather than organisation or system-wide. Remedies have included attention to leadership, change management and service culture. Through the same period, there have been changes to expand and strengthen health practitioner regulation, but scant attention to whether this regulation could contribute to difficulties with health service improvement. A critical realist methodology was used to build an explanation of how regulatory policies could condition health professionals and health service organisations in ways that limit the progress of service improvement. A multilevel approach was used to discover the mechanisms that could operate among policy-makers and the health workforce, generating effects in health service organisations. The study concluded that this explanation contributes new insights to explain persistent difficulties in health service improvement. The research began with the 19th century to understand the social conditions in the construction of the health workforce and health service organisations. Next, it identified the network of modern regulatory stakeholders in healthcare, along with the potential for their policies to operate in conflict or concert depending on the circumstances. Deficiencies were identified in the traditional accounts of health practitioner regulation, which assumes a single profession and sole practice. ‘Regulatory privilege’ was developed as an alternative theory that describes the operation of nine historically constructed regulatory levers among the multiple health professions employed in health service organisations. This theory linked the regulatory and practice levels, to observe the interactions between health practitioner regulation and policies for health service improvement. Drawing on the recent history of health reforms, eight elements were identified that characterise directions for service improvement in healthcare. Investigation of interactions between these nine levers and eight elements identified sources for policy interactions through six sector levels. Interactive effects were identified in: policy design influenced by health practitioner regulation; the leadership and management capability in health service organisations, the design options for delivery of services, the means available to coordinate services, the role opportunities and practice arrangements for health professionals, and the experience of service fragmentation by consumers. This multilevel explanation shows how health practitioner regulation could contribute to difficulties with service improvement, even when health services have adopted best practice in their implementations. It shows how poor alignment between the regulatory and practice levels makes it unlikely that health service organisations could address certain difficulties in the ways suggested by some scholars. Given the sustained directions for health service improvement, these findings could contribute to policy thinking around how to better align the regulatory and practice levels to realise organisation or systemwide improvements in the delivery of healthcare.</p>

The Role of Health Profession Regulation in Health Services Improvement

<p>This research investigates the role of health practitioner regulation in health service improvement. Over the last 25 years, service improvement has included management reforms, quality and redesign programmes, multidisciplinary teamwork, the integration of clinical information systems, and new roles for health professionals. Yet despite sustained effort, improvements tend to be localised rather than organisation or system-wide. Remedies have included attention to leadership, change management and service culture. Through the same period, there have been changes to expand and strengthen health practitioner regulation, but scant attention to whether this regulation could contribute to difficulties with health service improvement. A critical realist methodology was used to build an explanation of how regulatory policies could condition health professionals and health service organisations in ways that limit the progress of service improvement. A multilevel approach was used to discover the mechanisms that could operate among policy-makers and the health workforce, generating effects in health service organisations. The study concluded that this explanation contributes new insights to explain persistent difficulties in health service improvement. The research began with the 19th century to understand the social conditions in the construction of the health workforce and health service organisations. Next, it identified the network of modern regulatory stakeholders in healthcare, along with the potential for their policies to operate in conflict or concert depending on the circumstances. Deficiencies were identified in the traditional accounts of health practitioner regulation, which assumes a single profession and sole practice. ‘Regulatory privilege’ was developed as an alternative theory that describes the operation of nine historically constructed regulatory levers among the multiple health professions employed in health service organisations. This theory linked the regulatory and practice levels, to observe the interactions between health practitioner regulation and policies for health service improvement. Drawing on the recent history of health reforms, eight elements were identified that characterise directions for service improvement in healthcare. Investigation of interactions between these nine levers and eight elements identified sources for policy interactions through six sector levels. Interactive effects were identified in: policy design influenced by health practitioner regulation; the leadership and management capability in health service organisations, the design options for delivery of services, the means available to coordinate services, the role opportunities and practice arrangements for health professionals, and the experience of service fragmentation by consumers. This multilevel explanation shows how health practitioner regulation could contribute to difficulties with service improvement, even when health services have adopted best practice in their implementations. It shows how poor alignment between the regulatory and practice levels makes it unlikely that health service organisations could address certain difficulties in the ways suggested by some scholars. Given the sustained directions for health service improvement, these findings could contribute to policy thinking around how to better align the regulatory and practice levels to realise organisation or systemwide improvements in the delivery of healthcare.</p>

The BCM rule allows a spinal cord model to learn rhythmic movements

Animal locomotion is hypothesized to be controlled by a central pattern generator in the spinal cord. Experiments and models show that rhythm generating neurons and genetically determined network properties could sustain oscillatory output activity suitable for locomotion. However, current CPG models do not explain how a spinal cord circuitry, which has the same basic genetic plan across species, can adapt to control the different biomechanical properties and locomotion patterns existing in these species. Here we demonstrate that rhythmic and alternating movements in pendulum models can be learned by a monolayer spinal cord circuitry model using the BCM learning rule, which has been previously proposed to explain learning in the visual cortex. These results provide an alternative theory to CPG models, because rhythm generating neurons and genetically defined connectivity are not required in our model.