We propose that hyper‐inflammation (HYPi) is a ‘‘runaway’’ consequence of acute inflammation (ACUi) that arises more easily (and also abates less easily) in those who host a pre‐existing chronic inflammation (CHRi), because (i) most factors involved in generating an ACUi to limit viral proliferation are already present when there is an underlying CHRi, and also because (ii) anti‐inflammatory (AI) mechanisms for the abatement of ACUi (following containment of viral proliferation) are suppressed and desensitized where there is an underlying CHRi, with (...) this causing the ACUi to spiral into a HYPi. Stress, pollution, diet, and gut microbiomes (alterable in weeks through dietary changes) have an intimate and bidirectional cause‐effect relationship with CHRi. We propose that avoidance of CHRi‐promoting foods and adoption of CHRi‐suppressing foods could reduce susceptibility to HYPi, in Covid‐19 and in other viral diseases, such as influenza, which are characterized by episodic and unpredictable HYPi. (shrink)

This paper criticizes two closely connected rationalist views about human agency. The first of these views, rationalism about agential control, claims that the capacities for agential control in normal adult human beings are rational capacities. The second view, rationalism about action, claims that the capacities for agential control in virtue of which the things we do count as our actions are rational capacities. The arguments of the paper focus on aspects of technical skills that control integral details of skillful action, (...) like the details of a baseball player’s pitching technique. I argue that these aspects of technical skills are largely non-rational capacities, but are nonetheless capacities for agential control, and can help make the things we do count as actions. While rational capacities do have a central role in human agency, their importance should not lead us to neglect the significant constitutive role of non-rational capacities in our agency. (shrink)

Over 80% of the genes in the E. coli chromosome express fewer than a hundred copies each of their protein products per cell. It is argued here that transcription of these genes is neither constitutive nor regulated by protein factors, but rather, induced by the act of replication. The utility of such replication‐induced (RI) transcription to the temporal regulation of synthesis of determinate quantities of low copy number (LCN) proteins is described. It is suggested that RI transcription may be necessitated, (...) as well as facilitated, by the folding of the bacterial chromosome into a compact nucleoid. Mechanistic aspects of the induction of transcription by replication are discussed with respect to the modulation of transcriptional initiation by negative supercoiling effects, promoter methylation status and derepression. It is shown that RI transcription offers plausible explanations for the constancy of the C period of the E. coli cell cycle and the remarkable conservation of gene order in the chromosomes of enteric bacteria. Some experimental tests of the hypothesis are proposed. (shrink)

A simple introduction to numbers and their meanings.

Transcription and DNA supercoiling are known to be linked by a cause‐effect relationship that operates in both directions. It is proposed here that this two‐way relationship may be exploited by the E. coli genome to facilitate constitutive transcription of supercoil‐sensitive genes by polymerase batteries made up of uniformly spaced RNA polymerase elongation complexes. Specifically, it is argued that (1) polymerases transcribing DNA in tandem cooperate to relax each other's transcription‐driven positive supercoils; and (2) negative supercoils driven upstream by elongation complexes (...) tend to be ‘harnessed’ and used to cooperatively (and periodically) initiate fresh transcription from promoters. Harnessing of transcription‐driven negative supercoils is thought to be achieved through the erection of protein barriers to the rotational upstream propagation of supercoils from transcription events. The possible relevance of such cooperation amongst polymerases to the activation of transcription by DNA‐binding protein factors is emphasized. Some testable predictions are made and implications are discussed. (shrink)

A long-standing question in cognitive science is how high-level knowledge is integrated with sensory input. For example, listeners can leverage lexical knowledge to interpret an ambiguous speech sound, but do such effects reflect direct top-down influences on perception or merely postperceptual biases? A critical test case in the domain of spoken word recognition is lexically mediated compensation for coarticulation (LCfC). Previous LCfC studies have shown that a lexically restored context phoneme (e.g., /s/ in Christma#) can alter the perceived place of (...) articulation of a subsequent target phoneme (e.g., the initial phoneme of a stimulus from a tapes-capes continuum), consistent with the influence of an unambiguous context phoneme in the same position. Because this phoneme-to-phoneme compensation for coarticulation is considered sublexical, scientists agree that evidence for LCfC would constitute strong support for top–down interaction. However, results from previous LCfC studies have been inconsistent, and positive effects have often been small. Here, we conducted extensive piloting of stimuli prior to testing for LCfC. Specifically, we ensured that context items elicited robust phoneme restoration (e.g., that the final phoneme of Christma# was reliably identified as /s/) and that unambiguous context-final segments (e.g., a clear /s/ at the end of Christmas) drove reliable compensation for coarticulation for a subsequent target phoneme. We observed robust LCfC in a well-powered, preregistered experiment with these pretested items (N = 40) as well as in a direct replication study (N = 40). These results provide strong evidence in favor of computational models of spoken word recognition that include top–down feedback. (shrink)

This paper argues that you have non-observational warrant for beliefs about the body in action. For example, if you mean to be drinking a cup of water, you can know independently of observation that you are moving your body in a way that is effective in enabling you to drink. The case I make centers on the claim that you have default warrant to trust your agency. You do well to trust your agency just in virtue of your status as (...) an agent, and are not required to earn permission to trust your agency through making use of evidence about how well your agency works. You have non-observational warrant for beliefs about the functioning of your agency, including beliefs about your body in action, inasmuch as those beliefs reflect trust in your agency. (shrink)

There is widespread disagreement about whether epistemic akrasia is possible. This paper argues that the possibility of epistemic akrasia follows from a traditional rationalist conception of epistemic critical reasoning, together with considerations about the fallibility of our capacities for reasoning. In addition to defending the view that epistemic akrasia is possible, we aim to shed light on why it is possible. By focusing on critical epistemic reasoning, we show how traditional rationalist assumptions about our core cognitive capacities help to explain (...) the possibility of epistemic akrasia. (shrink)

While Aristotle claims that virtuous actions are choiceworthy for their own sakes, he also claims that many virtuous actions are to be chosen as instrumental means to securing further ends. It would seem that an action is choiceworthy for its own sake only if it would be choiceworthy whether or not it served further ends. How, then, can such virtuous actions be choiceworthy for their own sakes? This article criticizes John Ackrill's and Jennifer Whiting's answers to this question. I propose (...) an alternative, linking the choiceworthiness of virtuous actions to the pleasure, nobility, and beauty to be found in them. (shrink)

The purpose of this article is to study the use of “UP–DOWN” metaphors in Russian and French material. A list of 10 conceptual metaphors expressing up–down movement was proposed by CitationLakoff and Johnson (1980), and this list has been reproduced many times since. However, this analysis shows that the list is not fully accurate. In addition to the conceptual metaphors proposed by Lakoff and Johnson, the authors find it important to include 5 more metaphorical models expressing vertical movement. On the (...) other hand, 5 of the conceptual metaphors in Lakoff and Johnson's list turned out not to be relevant to this analysis. The authors also attempt to describe the connections between different metaphoric models and observe that not all metaphoric models are equally important in their evidential and conceptual power. (shrink)

This paper attempts to theorise the labour and corporeal carcerability of the non-citizen non-subjects in contemporary democracies of the United States and India. I reappropriate Joy James’ framework of ‘Captive Maternals’ to understand the relationality between the undocumented, racialised, or incarcerated with the neo-liberal states that they inhabit and serve but where they do not belong. James describes Captive Maternals as those bodies subject to consumption by the democratic order in the tradition of slavery. I expand upon her framework to (...) argue that the dehumanisation of illegal ‘aliens’ and racially policed bodies not only challenges the notion of freedom in the modern democratic social organisation but rather manifests the fundamental correlation between democratic sovereignty and its exclusionary violence. This phenomenon internal to the workings of democracies challenges Hegel’s idealisation of the modern rational state as the most advanced form of government characterised primarily by freedom. Democracy also constitutes the exercise of necropolitical sovereignty which I interpret not as the right to kill but as the right to police and incarcerate. Against the Hegelian struggle for recognition (Anerkennung), I deliberate on the possibility of transcending to a less than fully-determined Sittlichkeit that does not rely upon reciprocal recognition. (shrink)

Visual word recognition is facilitated by the presence of orthographic neighbors that mismatch the target word by a single letter substitution. However, researchers typically do not consider where neighbors mismatch the target. In light of evidence that some letter positions are more informative than others, we investigate whether the influence of orthographic neighbors differs across letter positions. To do so, we quantify the number of enemies at each letter position (how many neighbors mismatch the target word at that position). Analyses (...) of reaction time data from a visual word naming task indicate that the influence of enemies differs across letter positions, with the negative impacts of enemies being most pronounced at letter positions where readers have low prior uncertainty about which letters they will encounter (i.e., positions with low entropy). To understand the computational mechanisms that give rise to such positional entropy effects, we introduce a new computational model, VOISeR (Visual Orthographic Input Serial Reader), which receives orthographic inputs in parallel and produces an over‐time sequence of phonemes as output. VOISeR produces a similar pattern of results as in the human data, suggesting that positional entropy effects may emerge even when letters are not sampled serially. Finally, we demonstrate that these effects also emerge in human subjects' data from a lexical decision task, illustrating the generalizability of positional entropy effects across visual word recognition paradigms. Taken together, such work suggests that research into orthographic neighbor effects in visual word recognition should also consider differences between letter positions. (shrink)

In India, judicial review is not a static phenomenon. It has ensured that the Constitution is the supreme law of the land, and in situations when a law impinges on the rights and the liberties of citizens, it can be pruned or made void. This is a collection of scholarly essays demonstrating the different facets of judicial review based on the vast area of comparative constitutional law. Importantly, it honours the body of work of Upendra Baxi, legal scholar and author, (...) whose contributions have shaped our understanding of legal jurisprudence and expanded the scope of social transformation in India. This volume recognizes his role as an Indian jurist. Various constitutional law experts come together to reflect on his expositions on the role of the apex court, judicial activism, accountability of judiciary, laws on surrogacy and adultery and so on. (shrink)

Colonial ascidians offer opportunities to investigate how developmental events are integrated to generate the animal form, since they can develop similar individuals (oozooids from eggs, blastozooids from pluripotent somatic cells) through very different reproductive processes, i.e. embryogenesis and blastogenesis. Moreover, thanks to their key phylogenetic position, they can help in the understanding of the molecular mechanisms of morphogenesis and their evolution in chordates. We review organogenesis of the ascidian neural complex comparing embryos and buds in terms of topology, developmental mechanisms (...) and terminology. We propose a new interpretation of bud territories, and reconsider nervous system development based on recent results suggesting that ascidians have vertebrate placodal and neural‐crest‐like cells. Comparing embryonic and blastogenic development in Botryllus schlosseri, we propose that the bud has territories with a placodal potentiality, suggesting that chordate ancestors possessed neurogenic placodes, and that the genetic pathways regulating neurogenic placode formation were co‐opted for new developmental processes, such as blastogenesis. BioEssays 28: 902–912, 2006. © 2006 Wiley periodicals, Inc. (shrink)

Fission of cellular membranes is ubiquitous and essential for life. Complex protein machineries, such as the dynamin and ESCRT spirals, have evolved to mediate membrane fission during diverse cellular processes, for example, vesicle budding. A new study suggests that non-specialized membrane-bound proteins can induce membrane fission through mass action due to protein crowding. Because up to 2/3 of the mass of cellular membranes is contributed by proteins, membrane protein crowding is an important physiological parameter. Considering the complexity of membrane shape (...) transitions during a fission reaction, spatial and temporal variability in protein distribution, and the abundance of intrinsically disordered regions in proteins on an invaginating membrane, protein crowding can have diverse consequences for fission in the cell. The question is, how and to what extent this mechanism combines with the action of dedicated fission machineries. Membrane fission, which is required for formation of vesicles or cytokinesis, can be carried out by specialized proteins like dynamin and the ESCRT complex. Recent work suggests that fission of cellular membranes, which are densely packed with proteins, can also be induced by protein crowding due to high entropic tension. (shrink)

Denis Diderot’s ideas about war and peace crystalize many of the contradictions in the world that he identified. On the one hand, war is a natural product of contradictions between natural law and human developments. On the other hand, it can and should always be subject to moral judgment based on a wide-ranging knowledge of history and context. War can be good if it eliminates tyranny, and bad if it limits freedom, equality, and prosperity. Peace can be good if it (...) cultivates the latter, and bad if it freezes inequality. Diderot never allows himself to rest on universal judgments for all times and all places, but insists upon never-ending comparisons and contrasts between the moral world and the natural world. Philosophical materialism provides the basis for his understanding of the world, but morals provide the instruments of judgment. (shrink)

REM sleep behaviour disorder is a REM sleep-related parasomnia which may be considered a “dissociated state of wakefulness and sleep”, given that conflicting elements of REM sleep and of wakefulness coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson’s disease have full-blown RBD.Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this (...) parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs.Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs. (shrink)

New Blackfriars, Volume 103, Issue 1104, Page 309-316, March 2022.

Jacques le fataliste et son maître,1 Diderot’s “novel that is not a novel,” has no beginning and multiple endings. The narrator lacks credibility, is dismissive or even rude to the reader, and actually strives to be boring. The flow of narration is interrupted no less than fifty-one times, often just so the narrator can relish his power to direct the story. The fictional reader, a character embedded in the narrative, asks no fewer than forty-seven questions, usually requesting clarification, sometimes registering (...) complaints. Entire sections of Jacques have been unceremoniously copied from Laurence Sterne’s Tristram Shandy. It was generally judged a critical failure: for a hundred years after Jacques’s.. (shrink)

Despite the lack of invariance problem (the many‐to‐many mapping between acoustics and percepts), human listeners experience phonetic constancy and typically perceive what a speaker intends. Most models of human speech recognition (HSR) have side‐stepped this problem, working with abstract, idealized inputs and deferring the challenge of working with real speech. In contrast, carefully engineered deep learning networks allow robust, real‐world automatic speech recognition (ASR). However, the complexities of deep learning architectures and training regimens make it difficult to use them to (...) provide direct insights into mechanisms that may support HSR. In this brief article, we report preliminary results from a two‐layer network that borrows one element from ASR, long short‐term memory nodes, which provide dynamic memory for a range of temporal spans. This allows the model to learn to map real speech from multiple talkers to semantic targets with high accuracy, with human‐like timecourse of lexical access and phonological competition. Internal representations emerge that resemble phonetically organized responses in human superior temporal gyrus, suggesting that the model develops a distributed phonological code despite no explicit training on phonetic or phonemic targets. The ability to work with real speech is a major advance for cognitive models of HSR. (shrink)

Developing countries are endeavoring to advance into the 21st century information age. Their progress, however, is hamstrung by the dire lack of trained, skilled and knowledgeable IS workers who are able to interact with online and off‐line information sources. These countries can tap from the rich intellectual capital lying dormant within the ranks of disabled people to boost the pool of IS workers in their societies. However, before developing countries can draw on the information systems capabilities of disabled workers, these (...) workers themselves must be able to function at par with their able‐bodied counterparts as information workers. This presupposes the availability of special‐purpose information systems devices and approaches developed for disabled users. In this paper, therefore, we examine several issues that are pertinent to IS and disabled people in developing countries, and propose an integrated infrastructure to enhance the interaction of disabled people with on‐line information sources. The study includes issues related to the suitability of different interaction methodologies and technologies for people with disabilities. Additionally, we propose the design of customized interfaces that can be used by disabled people to develop Web‐based database applications and to access and query on‐line databases. (shrink)

Daniel Dennett, in Darwin's Dangerous Idea, argues that natural selection is a universal acid that eats through other theories, because it can explain just about everything, even the structure of the mind. Emanuel Schegloff in ‘Between Micro and Macro: Context and Other Connections’ opposes the importation of ‘macro’ factors into the ‘micro’, suggesting that one might reverse the strategy instead. Like Darwin, he is coy about whether he just wants his own turf, but the idea opens up the possibility of (...) interactional reductionism. I will argue against interactional reductionism on methodological grounds: Don't bite off more than you can chew! Instead I'll support the good old Durkheimian strategy of looking for intermediate variables between systems of different orders. I try and make the case with data from Rossel Island, Papua New Guinea. (shrink)