Shaftesbury on the beauty of nature

Many people today glorify wild nature. This attitude is diametrically opposed to the denigration of wild nature that was common in the seventeenth century. One of the most significant initiators of the modern revaluation of nature was Anthony Ashley Cooper, the third Earl of Shaftesbury (1671–1713). I elucidate here Shaftesbury’s pivotal view of nature. I show how that view emerged as Shaftesbury’s solution to a problem he took to be of the deepest philosophical and personal importance: the problem of how worship of God can be both transportingly emotional and entirely rational. In section 1 I sketch the denigration of wild nature in two of Shaftesbury’s predecessors: Burnet and Locke. I next turn to Shaftesbury’s problem, describing in section 2 the love of God he aspired to and in section 3 his commitment to rational religion. I then explain Shaftesbury’s solution, describing in section 4 his view of beauty in general and in section 5 his view of the beauty of nature

A geometric proof of the Kochen-Specker no-go theorem

We give a short geometric proof of the Kochen-Specker no-go theorem for non-contextual hidden variables models. Note added to this version: I understand from Jan-Aake Larsson that the construction we give here actually contains the original Kochen-Specker construction as well as many others (Bell, Conway and Kochen, Schuette, perhaps also Peres).Comment: This paper appeared some years ago, before the author was aware of quant-ph. It is relevant to recent developments concerning Kochen-Specker theorem

KSHV-TK is a tyrosine kinase that disrupts focal adhesions and induces Rho-mediated cell contraction.

This is the accepted manuscript. The final version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.15252/embj.201490358/abstract.Paradoxically, the thymidine kinase (TK) encoded by Kaposi sarcoma-associated herpesvirus (KSHV) is an extremely inefficient nucleoside kinase, when compared to TKs from related herpesviruses. We now show that KSHV-TK, in contrast to HSV1-TK, associates with the actin cytoskeleton and induces extensive cell contraction followed by membrane blebbing. These dramatic changes in cell morphology depend on the auto-phosphorylation of tyrosines 65, 85 and 120 in the N-terminus of KSHV-TK. Phosphorylation of tyrosines 65/85 and 120 results in an interaction with Crk family proteins and the p85 regulatory subunit of PI3-Kinase, respectively. The interaction of Crk with KSHV-TK leads to tyrosine phoshorylation of this cellular adaptor. Auto-phosphorylation of KSHV-TK also induces a loss of FAK and paxillin from focal adhesions, resulting in activation of RhoA-ROCK signalling to myosin II and cell contraction. In the absence of FAK or paxillin, KSHV-TK has no effect on focal adhesion integrity or cell morphology. Our observations demonstrate that by acting as a tyrosine kinase, KSHV-TK modulates signalling and cell morphology.This work was supported by Medical Research Council grant G0701185 to PGS and MBG. M.W is supported by Cancer Research UK

Down-regulation of CD46 by Piliated Neisseria gonorrhoeae

Human membrane cofactor protein (CD46) protects host cells against complement attack and may function as a receptor for pathogenic Neisseriae. We assessed CD46 expression in the human cervical cell line ME-180 after exposure to Neisseria gonorrhoeae. Piliated but not nonpiliated gonococci adhered to cells and produced up to an 80% reduction in CD46 surface expression by 6 h that persisted for at least 24 h. This response required a minimum multiplicity of infection of 10 and was not prevented by antibodies to CD46. CD46 down-regulation was not attributable to intracellular retention or a global or specific shutdown of mRNA or protein synthesis. Substantial quantities of CD46 were found in the supernatants, indicating a specific shedding of this protein. Adherent gonococci lacking the pilus retraction protein PilT did not down-regulate CD46 but de-repression of pilT expression restored CD46 down-regulation. After experimental infection of human volunteers with a gonococcal variant incapable of inducing CD46 down-regulation, variants of this strain were reisolated that exhibited CD46 down-regulation. Pilus-mediated interactions of gonococci with human epithelial cells results in a pathogen-induced manipulation of the host cell environment in which a membrane protein is removed from epithelial cells by liberation into the surrounding milieu

2008. Sentimentalist pluralism: moral psychology and philosophical ethics

When making moral judgments, people are typically guided by a plurality of moral rules. These rules owe their existence to human emotions but are not simply equivalent to those emotions. And people's moral judgments ought to be guided by a plurality of emotion-based rules. The view just stated combines three positions on moral judgment: [1] moral sentimentalism, which holds that sentiments play an essential role in moral judgment, 1 [2] descriptive moral pluralism, which holds that commonsense moral judgment is guided by a plurality of moral rules, 2 and [3] prescriptive moral pluralism, which holds that moral judgment ought to be guided by a plurality of moral rules. In what follows, we will argue for all three positions. We will not present a comprehensive case for these positions nor address many of the arguments philosophers have developed against them. What we will try to show is that recent psychological work supports sentimentalist pluralism in both its descriptive and prescriptive forms

Development of the ChatGPT, Generative Artificial Intelligence and Natural Large Language Models for Accountable Reporting and Use (CANGARU) Guidelines

The swift progress and ubiquitous adoption of Generative AI (GAI), Generative Pre-trained Transformers (GPTs), and large language models (LLMs) like ChatGPT, have spurred queries about their ethical application, use, and disclosure in scholarly research and scientific productions. A few publishers and journals have recently created their own sets of rules; however, the absence of a unified approach may lead to a 'Babel Tower Effect,' potentially resulting in confusion rather than desired standardization. In response to this, we present the ChatGPT, Generative Artificial Intelligence, and Natural Large Language Models for Accountable Reporting and Use Guidelines (CANGARU) initiative, with the aim of fostering a cross-disciplinary global inclusive consensus on the ethical use, disclosure, and proper reporting of GAI/GPT/LLM technologies in academia. The present protocol consists of four distinct parts: a) an ongoing systematic review of GAI/GPT/LLM applications to understand the linked ideas, findings, and reporting standards in scholarly research, and to formulate guidelines for its use and disclosure, b) a bibliometric analysis of existing author guidelines in journals that mention GAI/GPT/LLM, with the goal of evaluating existing guidelines, analyzing the disparity in their recommendations, and identifying common rules that can be brought into the Delphi consensus process, c) a Delphi survey to establish agreement on the items for the guidelines, ensuring principled GAI/GPT/LLM use, disclosure, and reporting in academia, and d) the subsequent development and dissemination of the finalized guidelines and their supplementary explanation and elaboration documents.Comment: 20 pages, 1 figure, protoco

Bibliometric Analysis of Publisher and Journal Instructions to Authors on Generative-AI in Academic and Scientific Publishing

We aim to determine the extent and content of guidance for authors regarding the use of generative-AI (GAI), Generative Pretrained models (GPTs) and Large Language Models (LLMs) powered tools among the top 100 academic publishers and journals in science. The websites of these publishers and journals were screened from between 19th and 20th May 2023. Among the largest 100 publishers, 17% provided guidance on the use of GAI, of which 12 (70.6%) were among the top 25 publishers. Among the top 100 journals, 70% have provided guidance on GAI. Of those with guidance, 94.1% of publishers and 95.7% of journals prohibited the inclusion of GAI as an author. Four journals (5.7%) explicitly prohibit the use of GAI in the generation of a manuscript, while 3 (17.6%) publishers and 15 (21.4%) journals indicated their guidance exclusively applies to the writing process. When disclosing the use of GAI, 42.8% of publishers and 44.3% of journals included specific disclosure criteria. There was variability in guidance of where to disclose the use of GAI, including in the methods, acknowledgments, cover letter, or a new section. There was also variability in how to access GAI guidance and the linking of journal and publisher instructions to authors. There is a lack of guidance by some top publishers and journals on the use of GAI by authors. Among those publishers and journals that provide guidance, there is substantial heterogeneity in the allowable uses of GAI and in how it should be disclosed, with this heterogeneity persisting among affiliated publishers and journals in some instances. The lack of standardization burdens authors and threatens to limit the effectiveness of these regulations. There is a need for standardized guidelines in order to protect the integrity of scientific output as GAI continues to grow in popularity.Comment: Pages 16, 1 figure, 2 table

Genetic Classification of Populations using Supervised Learning

There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case--control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed \emph{unsupervised}. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available. In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies.Comment: Accepted PLOS On

In vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit

The difficulty of eliminating herpesvirus carriage makes host entry a key target for infection control. However, its viral requirements are poorly defined. Murid herpesvirus-4 (MuHV-4) can potentially provide insights into gammaherpesvirus host entry. Upper respiratory tract infection requires the MuHV-4 thymidine kinase (TK) and ribonucleotide reductase large subunit (RNR-L), suggesting a need for increased nucleotide production. However, both TK and RNR-L are likely to be multifunctional. We therefore tested further the importance of nucleotide production by disrupting the MuHV-4 ribonucleotide reductase small subunit (RNR-S). This caused a similar attenuation to RNR-L disruption: despite reduced intra-host spread, invasive inoculations still established infection, whereas a non-invasive upper respiratory tract inoculation did so only at high dose. Histological analysis showed that RNR-S−, RNR-L− and TK− viruses all infected cells in the olfactory neuroepithelium but unlike wild-type virus then failed to spread. Thus captured host nucleotide metabolism enzymes, up to now defined mainly as important for alphaherpesvirus reactivation in neurons, also have a key role in gammaherpesvirus host entry. This seemed to reflect a requirement for lytic replication to occur in a terminally differentiated cell before a viable pool of latent genomes could be established