How We Reason Johnson-Laird, Philip
2008, 2006, 2008-10-23
eBook
Good reasoning can lead to success; bad reasoning can lead to catastrophe. Yet, it's not obvious how we reason, and why we make mistakes. This new book by one of the pioneers of the field, Philip ...Johnson-Laird, looks at the mental processes that underlie our reasoning. It provides the most accessible account yet of the science of reasoning.
We show that malicious COVID-19 content, including racism, disinformation, and misinformation, exploits the multiverse of online hate to spread quickly beyond the control of any individual social ...media platform. We provide a first mapping of the online hate network across six major social media platforms. We demonstrate how malicious content can travel across this network in ways that subvert platform moderation efforts. Machine learning topic analysis shows quantitatively how online hate communities are sharpening COVID-19 as a weapon, with topics evolving rapidly and content becoming increasingly coherent. Based on mathematical modeling, we provide predictions of how changes to content moderation policies can slow the spread of malicious content.
Disrupting the emergence and evolution of potentially violent online extremist movements is a crucial challenge. Extremism research has analyzed such movements in detail, focusing on individual- and ...movement-level characteristics. But are there system-level commonalities in the ways these movements emerge and grow? Here we compare the growth of the Boogaloos, a new and increasingly prominent U.S. extremist movement, to the growth of online support for ISIS, a militant, terrorist organization based in the Middle East that follows a radical version of Islam. We show that the early dynamics of these two online movements follow the same mathematical order despite their stark ideological, geographical, and cultural differences. The evolution of both movements, across scales, follows a single shockwave equation that accounts for heterogeneity in online interactions. These scientific properties suggest specific policies to address online extremism and radicalization. We show how actions by social media platforms could disrupt the onset and 'flatten the curve' of such online extremism by nudging its collective chemistry. Our results provide a system-level understanding of the emergence of extremist movements that yields fresh insight into their evolution and possible interventions to limit their growth.
Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a ...fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype) into four (TNBCtype-4) tumor-specific subtypes (BL1, BL2, M and LAR) and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50) or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; 33, 51, 9, 28, 17, 41, respectively). Collectively, we provide pre-clinical data that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.
Having long been debated, it is only in the last few years that a concensus has emerged that the cyclic flow of electrons around Photosystem I plays an important and general role in the ...photosynthesis of higher plants. Two major pathways of cyclic flow have been identified, involving either a complex termed NDH or mediated via a pathway involving a protein PGR5 and two functions have been described—to generate ATP and to provide a pH gradient inducing non-photochemical quenching. The best evidence for the occurrence of the two pathways comes from measurements under stress conditions—high light, drought and extreme temperatures. In this review, the possible relative functions and importance of the two pathways is discussed as well as evidence as to how the flow through these pathways is regulated. Our growing knowledge of the proteins involved in cyclic electron flow will, in the future, enable us to understand better the occurrence and diversity of cyclic electron transport pathways. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts.
► Cyclic electron flow around Photosystem I has been shown to play an essential role in photosynthesis. ► Cyclic flow makes ATP and protects plants from stress by triggering non photochemical quenching. ► Two distinct pathways of cyclic flow exist, the PGR5 and the NDH pathways. ► Regulation of cyclic flow probably occurs though competition for oxidising ferredoxin.
Toothbrushing is considered fundamental self-care behavior for maintenance of oral health, and brushing twice a day has become a social norm, but the evidence base for this frequency is weak. This ...systematic review and meta-analysis aims to assess the effect of toothbrushing frequency on the incidence and increment of carious lesions. Medline, Embase, Cinahl, and Cochrane databases were searched. Screening and quality assessment were performed by 2 independent reviewers. Three different meta-analyses were conducted: 2 based on the caries outcome reported in the studies (incidence and increment) with subgroup analyses of categories of toothbrushing frequency; another included all studies irrespective of the caries outcome reported with the type of dentition as subgroups. Meta-regression was conducted to assess the influence of sample size, follow-up period, diagnosis level for carious lesions, and methodological quality of the articles on the effect estimate. Searches retrieved 5,494 titles: after removing duplicates, 4,305 remained. Of these, 74 were reviewed in full, but only 33 were eligible for inclusion. Self-reported infrequent brushers demonstrated higher incidence (odds ratio OR, 1.50; 95% confidence interval CI, 1.34 to 1.69) and increment (standardized mean difference SMD, 0.28; 95% CI: 0.13 to 0.44) of carious lesions than frequent brushers. The odds of having carious lesions differed little when subgroup analysis was conducted to compare the incidence between ≥2 times/d vs <2 times/d (OR: 1.45; 95% CI: 1.21 to 1.74) and ≥1 time/d vs <1 time/d brushers (OR: 1.56; 95% CI: 1.37 to 1.78). When meta-analysis was conducted with the type of dentition as subgroups, the effect of infrequent brushing on incidence and increment of carious lesions was higher in deciduous (OR: 1.75; 95% CI: 1.49 to 2.06) than permanent dentition (OR: 1.39; 95% CI: 1.29 to 1.49). Findings from meta-regression indicated that none of the included variables influenced the effect estimate.
Cyclic electron flow is increasingly recognized as being essential in plant growth, generating a pH gradient across thylakoid membrane (ΔpH) that contributes to ATP synthesis and triggers the ...protective process of nonphotochemical quenching (NPQ) under stress conditions. Here, we report experiments demonstrating the importance of that ΔpH in protecting plants from stress and relating to the regulation of cyclic relative to linear flow. In leaves infiltrated with low concentrations of nigericin, which dissipates the ΔpH without significantly affecting the potential gradient, thereby maintaining ATP synthesis, the extent of NPQ was markedly lower, reflecting the lower ΔpH. At the same time, the photosystem (PS) I primary donor P700 was largely reduced in the light, in contrast to control conditions where increasing light progressively oxidized P700, due to down-regulation of the cytochrome bf complex. Illumination of nigericin-infiltrated leaves resulted in photoinhibition of PSII but also, more markedly, of PSI. Plants lacking ferredoxin (Fd) NADP oxidoreductase (FNR) or the polypeptide proton gradient regulation 5 (PGR5) also show reduction of P700 in the light and increased sensitivity to PSI photoinhibition, demonstrating that the regulation of the cytochrome bf complex (cyt bf) is essential for protection of PSI from light stress. The formation of a ΔpH is concluded to be essential to that regulation, with cyclic electron flow playing a vital, previously poorly appreciated role in this protective process. Examination of cyclic electron flow in plants with a reduced content of FNR shows that these antisense plants are less able to maintain a steady rate of this pathway. This reduction is suggested to reflect a change in the distribution of FNR from cyclic to linear flow, likely reflecting the formation or disassembly of FNR–cytochrome bf complex.
Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases regulate signalling pathways and cellular processes that mediate metabolism, transcription, cell-cycle ...progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. Protein kinases share a conserved catalytic domain, which catalyses the transfer of the gamma-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. The kinase can exist in an active or inactive state regulated by a variety of mechanisms in different kinases that include control by phosphorylation, regulation by additional domains that may target other molecules, binding and regulation by additional subunits, and control by protein-protein association. This Novartis Medal Lecture was delivered at a meeting on protein evolution celebrating the 200th anniversary of Charles Darwin's birth. I begin with a summary of current observations from protein sequences of kinase phylogeny. I then review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase to illustrate one of the more dramatic consequences of phosphorylation. Regulation of protein phosphorylation is frequently disrupted in the diseased state, and protein kinases have become high-profile targets for drug development. Finally, I consider recent advances on protein kinases as drug targets and describe some of our recent work with CDK9 (cyclin-dependent kinase 9)-cyclin T, a regulator of transcription.
There is growing recognition of the important roles played by predators in regulating ecosystems and sustaining biodiversity. Much attention has focused on the consequences of predator-regulation of ...herbivore populations, and associated trophic cascades. However apex predators may also control smaller 'mesopredators' through intraguild interactions. Removal of apex predators can result in changes to intraguild interactions and outbreaks of mesopredators ('mesopredator release'), leading in turn to increased predation on smaller prey. Here we provide a review and synthesis of studies of predator interactions, mesopredator release and their impacts on biodiversity. Mesopredator suppression by apex predators is widespread geographically and taxonomically. Apex predators suppress mesopredators both by killing them, or instilling fear, which motivates changes in behaviour and habitat use that limit mesopredator distribution and abundance. Changes in the abundance of apex predators may have disproportionate (up to fourfold) effects on mesopredator abundance. Outcomes of interactions between predators may however vary with resource availability, habitat complexity and the complexity of predator communities. There is potential for the restoration of apex predators to have benefits for biodiversity conservation through moderation of the impacts of mesopredators on their prey, but this requires a whole-ecosystem view to avoid unforeseen negative effects. 'Nothing has changed since I began. My eye has permitted no change. I am going to keep things like this.' From 'Hawk Roosting', by Ted Hughes.
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