Non-Gods and Gods: A Cosmontological Treatise

Incorporating the conceptual resources of the ontological argument for the existence of God into the underlying rationale of the cosmological ditto, I here present and defend a ‘cosmontological’ synthesis: an a posteriori argument for the existence of an all-perfect GOD: a being who, in virtue of being whatever it is better to be than not to be, is that than which a greater cannot be thought. Central to this synthesis is a very plausible principle called Exclusion: For any class (or property extension) C, if C is non-empty then there is an explanation for the non-emptiness of C if and only if there is at least one non-member of C which causes C to be non-empty. Applying this principle to the non-empty class of non-GODs, it follows that the non-emptiness of this class – the fact that there is at least one non-GOD – has an explanation if and only if it has been effectuated by at least one GOD. But the non-emptiness of this class has an explanation – or at least there is a fairly strong epistemic reason to think so. Accordingly, in the final analysis, the cosmontological argument proffers a fairly strong epistemic reason to postulate the existence of at least one (in fact, exactly one) GOD. Of course, the notion of ‘GOD’ is in need of much illumination. To begin with, ‘whatever it is better to be than not to be’ needs to be analyzed in a non-relative and yet meaningful way. Attempting such an analysis, I am able to deduce a great number of essential characteristics traditionally predicated of that than which a greater cannot be thought. Two of the most important of these characteristics, namely, omniscience and omnipotence, are then singled out for particular scrutiny. Omniscience (defined, roughly, as knowledge of all truths) is successfully defended against three lines of attack: the argument from essential indexicals, the argument from power sets, and the argument from theological fatalism. Omnipotence, which is a far more elusive property, is then likewise defended against different charges of incompossibility with other allegedly divine attributes, in particular, essential impeccability. I also venture, and try to substantiate, a new and distinctively metaphysical account of what omnipotence is. Roughly, according to this account, an agent A is omnipotent if and only if (i) A is incomparably more powerful than any other possible agent, and (ii) the possibility of any other agent is created by A

Francis Jonbäck, Meningslöst lidande

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Varför finns det sådant som inte måste finnas?

Not only the argument from contingency for the existence of God but also the theistic idea that God is the metaphysical foundation of the world seem to presuppose the intelligibility and validity of the following question: Why is there anything contingent at all? However, it has been argued that, upon closer inspection, this question is a pseudo-question: a question which presupposes illegitimate or somehow ill-founded assumptions. In this article I respond to some of this criticism, especially to that given by David Hume and Adolf Grünbaum. I argue that there seems to be no good reason to think that the question under consideration should not continue to receive proper philosophical attention

Dispersal of Group A Streptococcal Biofilms by the Cysteine Protease SpeB Leads to Increased Disease Severity in a Murine Model

Group A Streptococcus (GAS) is a Gram-positive human pathogen best known for causing pharyngeal and mild skin infections. However, in the 1980's there was an increase in severe GAS infections including cellulitis and deeper tissue infections like necrotizing fasciitis. Particularly striking about this elevation in the incidence of severe disease was that those most often affected were previously healthy individuals. Several groups have shown that changes in gene content or regulation, as with proteases, may contribute to severe disease; yet strains harboring these proteases continue to cause mild disease as well. We and others have shown that group A streptococci (MGAS5005) reside within biofilms both in vitro and in vivo. That is to say that the organism colonizes a host surface and forms a 3-dimensional community encased in a protective matrix of extracellular protein, DNA and polysaccharide(s). However, the mechanism of assembly or dispersal of these structures is unclear, as is the relationship of these structures to disease outcome. Recently we reported that allelic replacement of the streptococcal regulator srv resulted in constitutive production of the streptococcal cysteine protease SpeB. We further showed that the constitutive production of SpeB significantly decreased MGAS5005Δsrv biofilm formation in vitro. Here we show that mice infected with MGAS5005Δsrv had significantly larger lesion development than wild-type infected animals. Histopathology, Gram-staining and immunofluorescence link the increased lesion development with lack of disease containment, lack of biofilm formation, and readily detectable levels of SpeB in the tissue. Treatment of MGAS5005Δsrv infected lesions with a chemical inhibitor of SpeB significantly reduced lesion formation and disease spread to wild-type levels. Furthermore, inactivation of speB in the MGAS5005Δsrv background reduced lesion formation to wild-type levels. Taken together, these data suggest a mechanism by which GAS disease may transition from mild to severe through the Srv mediated dispersal of GAS biofilms

Two Group A Streptococcal Peptide Pheromones Act through Opposing Rgg Regulators to Control Biofilm Development

Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the Firmicute phylum

Nonmedical prescription psychiatric drug use and the darknet: A cryptomarket analysis

Nonmedical prescription psychiatric drug use (NMPDU) is an increasing global health problem, with recent concern focusing on darknet cryptomarkets as sources of procurement. There is a shortage of evidence regarding comparative worldwide NMPDU trends, due in part to data collection difficulties. This problem is particularly marked for non-opioid drugs, particularly those psychiatric drugs which act on the central nervous system (CNS) and have high misuse potential and are associated with high levels of dependency and fatal overdose. This paper therefore has two goals: 1) to report on the kinds of psychiatric prescription drugs available on cryptomarkets, and 2) to use this data to uncover temporal and geographical trends in sales of these products, potentially informing policy regarding NMPDU more generally. Method Digital trace data collected from 31 cryptomarkets in operation between September 2013 and July 2016 was analysed by country of origin descriptively and for trends in the sales for 7 psychiatric drug groupings, based on their main indication or intended use in psychiatric practice. Results Sedatives (such as diazepam and alprazolam) and CNS stimulants (mainly Adderall, modafinil and methylphenidate) had the greatest share of sales, but usage and trends varied by location. The UK has high and rising levels of sedative sales, whilst the USA has the greatest stimulant sales and increasing sedative rates. Sales of drugs used in the treatment of opioid dependency are also substantial in the USA. The picture is less clear in mainland Europe with high sales levels reported in unexpected Central and Northern European countries. There is evidence of a move towards the more potent sedative alprazolam – already implicated as a source of problematic NMPDU in the USA – in Australia and the UK. Sales of drugs such as antidepressants, antipsychotics, mood stabilisers and antidementia drugs – all drugs with limited abuse potential – were negligible, indicating minimal levels of online cryptomarket procurement for self-medicating mental health problems. Conclusion Predominantly, psychiatric drugs with potent sedative, stimulant or euphoriant effects are sold on cryptomarkets and this varies by country. With some caveats regarding the limitations of cryptomarket digital trace data taken into account, the study of trends of these products sold online over time may offer a novel and increasingly important window onto wider drug purchasing habits

The tropical Atlantic observing system

The tropical Atlantic is home to multiple coupled climate variations covering a wide range of timescales and impacting societally relevant phenomena such as continental rainfall, Atlantic hurricane activity, oceanic biological productivity, and atmospheric circulation in the equatorial Pacific. The tropical Atlantic also connects the southern and northern branches of the Atlantic meridional overturning circulation and receives freshwater input from some of the world’s largest rivers. To address these diverse, unique, and interconnected research challenges, a rich network of ocean observations has developed, building on the backbone of the Prediction and Research Moored Array in the Tropical Atlantic (PIRATA). This network has evolved naturally over time and out of necessity in order to address the most important outstanding scientific questions and to improve predictions of tropical Atlantic severe weather and global climate variability and change. The tropical Atlantic observing system is motivated by goals to understand and better predict phenomena such as tropical Atlantic interannual to decadal variability and climate change; multidecadal variability and its links to the meridional overturning circulation; air-sea fluxes of CO2 and their implications for the fate of anthropogenic CO2; the Amazon River plume and its interactions with biogeochemistry, vertical mixing, and hurricanes; the highly productive eastern boundary and equatorial upwelling systems; and oceanic oxygen minimum zones, their impacts on biogeochemical cycles and marine ecosystems, and their feedbacks to climate. Past success of the tropical Atlantic observing system is the result of an international commitment to sustained observations and scientific cooperation, a willingness to evolve with changing research and monitoring needs, and a desire to share data openly with the scientific community and operational centers. The observing system must continue to evolve in order to meet an expanding set of research priorities and operational challenges. This paper discusses the tropical Atlantic observing system, including emerging scientific questions that demand sustained ocean observations, the potential for further integration of the observing system, and the requirements for sustaining and enhancing the tropical Atlantic observing system