Canonical Process Research Articles

Pyroptosis in asthma: inflammatory phenotypes, immune and non-immune cells, and novel treatment approaches

Pyroptosis is a form of inflammatory programmed cell death, and is activated by pathogen infections or endogenous danger signals. The canonical pyroptosis process is characterized by the inflammasome (typically NLRP3)-mediated activation of caspase-1, which in turn cleaves and activates IL-1β and IL-18, as well as gasdermin D, which is a pore-forming executor protein, leading to cell membrane rupture, and the release of proinflammatory cytokines and damage-associated molecular pattern molecules. Pyroptosis is considered a part of the innate immune response. A certain level of pyroptosis can help eliminate pathogenic microorganisms, but excessive pyroptosis can lead to persistent inflammatory responses, and cause tissue damage. In recent years, pyroptosis has emerged as a crucial contributor to the development of chronic inflammatory respiratory diseases, such as asthma. The present study reviews the involvement of pyroptosis in the development of asthma, in terms of its role in different inflammatory phenotypes of the disease, and its influence on various immune and non-immune cells in the airway. In addition, the potential therapeutic value of targeting pyroptosis for the treatment of specific phenotypes of asthma is discussed.

Le style pragmatique et commatique de Porphyre à Simplicius

Abstract In this study, we aim to analyze the notions of “pragmatic” and “commatic” we encounter in what we highlight to be a process of canonization of style appropriate to each content and theological level since Porphyry. This research is divided into three parts: primarily, we investigate the sense in which the Neoplatonists use the adjective “commatic”, which includes on the one hand (1) defining what the Neoplatonists mean by “unity of meaning”, and on the other hand distinguishing between a “woven” and continuous style and a “disjointed” and broken style, collecting the stylistic criticisms made by the Neoplatonists of the ancient texts; then (2) we seek to establish the areas of application of the “commatic” style in Neoplatonic discourse, distinguishing on the one hand inspired and ethical discourse, and on the other hand clear and sharp dialectical discourse, bordering on that which eludes philosophical demonstration, namely, the ἀσάφεια; finally (3), we aim to study the “pragmatic” style associated with each theological content in order to highlight its corresponding style and vocabulary. The present research stems from the need to show how behind the lexical and structural choices of the Neoplatonic writings there is a precise theory of style, produced by a process of aesthetic canonization that emerges clearly as early as Porphyry’s rhetorical fragments and from Neoplatonic exegetical activity on rhetorical works, as well as from an innumerable amount of references to a rhetorical tradition on the period and its parts, the commata and côla, which the Neoplatonists, as this study aims to show, master and apply on their own structuring and formalization of theological content.

Deceiving Dichotomies: On the Interrelation of the Archive and the Cultural Memory Canon

ABSTRACTThis paper explores the conceptual relationship between archives and canonization by amending Aleida Assmann's cultural memory framework of Canon and Archive to consider ongoing debates in archival theory and practice. The process of canonization concerns the selection, value, and duration of cultural memory. The formation and function of archives are marked by processes of appraisal (record evaluation and selection), acquisition (record transfer), and preservation (record duration). Placing A. Assmann's framework in conversation with the informational frameworks of de Fremery and Buckland, we observe how at any given time (a past/present context), records (documents) are selected (perception) because of their value in signaling memories and community histories (affordances) while serving as a durable medium for restabilizing identities (use) across time (a present/future context).

Measuring Irreversibility from Learned Representations of Biological Patterns

Thermodynamic irreversibility is a fundamental characteristic of living matter, crucial for maintaining the complex spatiotemporal structures and functions that define biological systems. However, accurately quantifying biologically relevant irreversibility remains challenging due to noise and nonlinear interactions among many degrees of freedom. Here, we employ deep learning techniques to identify tractable, low-dimensional representations of phase-field patterns in a canonical protein signaling process—the Rho-GTPase system—as well as in complex Ginzburg-Landau dynamics. We demonstrate that factorizing variational autoencoder neural networks can robustly extract informative pattern features despite noise. These neural-network-derived representations reveal signatures of mesoscopic broken detailed balance and time-reversal asymmetry in both Rho-GTPase and complex Ginzburg-Landau wave dynamics. By applying the compression-based Ziv-Merhav estimator to these representations, we successfully recover irreversibility trends across complex Ginzburg-Landau patterns, which vary widely in spatiotemporal frequency and noise level. Our irreversibility estimates also recapitulate cell-activity trends in Rho-GTPase patterns subjected to metabolic inhibition. Furthermore, our framework distinguishes between stable and chaotic dynamical phases in these nonlinear systems. By leveraging advances in deep learning, our approach provides robust, model-free measurements of nonequilibrium and nonlinear behavior in complex living processes. Published by the American Physical Society 2024

Traces of holiness: blessed women, holy women in the papers of diocesan archives

The article aims to focus attention on the study of blessed women and holy women through the documentation found in diocesan archives and belonging to the series of canonization processes. With the regulation of the process, narrative organization gave way to legal defense, confrontation to analysis, and narrative to texts that had evidentiary value, and all this gave rise to a mine of information not only about the lives of the blessed and holy women, but also about the society in which they had lived.

Photoprotective Melanin is Maintained Within Keratinocytes in Storage Lysosomes

In the skin, melanin is synthesized by melanocytes within melanosomes, and transferred to keratinocytes. After being phagocytosed by keratinocytes, melanin polarizes to supranuclear caps that protect against the genotoxic effects of ultraviolet radiation. We provide evidence that melanin-containing phagosomes undergo a canonical maturation process, with the sequential acquisition of early and late endosomal markers. Subsequently, these phagosomes fuse with active lysosomes, leading to the formation of a melanin-containing phagolysosome that we named melanokerasome. Melanokerasomes achieve juxtanuclear positioning via lysosomal trafficking regulators Rab7 and RILP. Mature melanokerasomes exhibit lysosomal markers, elude connections with the endo/phagocytic pathway, are weakly degradative, retain undigested cargo and are likely tethered to the nuclear membrane. We propose that they represent a lysosomal-derived storage compartment that has exited the lysosome cycle, akin to the formation of lipofuscin in aged cells and dysfunctional lysosomes in lysosomal storage and age-related diseases. This storage lysosome allows melanin to persist for long periods, where it can exert its photoprotective effect efficiently.

A Girsanov transformed Clark-Ocone-Haussmann type formula for $$L^1$$-pure jump additive processes and its application to portfolio optimization

AbstractWe derive a Clark-Ocone-Haussmann (COH) type formula under a change of measure for $$ L^1 $$ L 1 -canonical additive processes, providing a tool for representing financial derivatives under a risk-neutral probability measure. COH formulas are fundamental in stochastic analysis, providing explicit martingale representations of random variables in terms of their Malliavin derivatives. In mathematical finance, the COH formula under a change of measure is crucial for representing financial derivatives under a risk-neutral probability measure. To prove our main results, we use the Malliavin-Skorohod calculus in $$ L^0 $$ L 0 and $$ L^1 $$ L 1 for additive processes, as developed by Di Nunno and Vives (2017). An application of our results is solving the local risk minimization (LRM) problem in financial markets driven by pure jump additive processes. LRM, a prominent hedging approach in incomplete markets, seeks strategies that minimize the conditional variance of the hedging error. By applying our COH formula, we obtain explicit expressions for locally risk-minimizing hedging strategies in terms of Malliavin derivatives under the market model underlying the additive process. These formulas provide practical tools for managing risks in financial market price fluctuations with $$L^1$$ L 1 -additive processes.

Allegory and the Canonization of the Song of Songs

Abstract The canonical process that led to the inclusion of the Song of Songs in the lists of books of the Hebrew Bible or Old Testament is investigated with focus on the saying attributed to Rabbi Aqiva in Mishnah Yadayim 3:5, and also investigated is whether he referred to the Holy of Holies of the Jerusalem Temple. It is demonstrated that he asserted that all the writings are holy and the Song of Songs is holiest. But the framing of the mishnah associates all scriptures, including the Song of Songs, with the Temple, the Ark of the Covenant, and the Holy of Holies. Allegorical interpretation of the Song likely preceded the book’s canonization.

Doubly perturbed uncertain differential equations

In this paper, we study a class of doubly perturbed uncertain differential equations driven by canonical process that is the counterpart of Wiener process in the framework of uncertain theory. We give some sufficient conditions for the existence and uniqueness of solutions of the present problem under some weak conditions, where a convex combination of the Nagumo and Osgood conditions is considered. Subsequently, we consider the stability properties with regard to the initial value and coefficients. Finally, an example is provided to illustrate the effectiveness of our main results.

The dual nature of working memory deficits: methamphetamine abusers have more impaired social working memory capacity than canonical working memory capacity.

Social working memory (WM) temporarily retains and manipulates various aspects of social information. Extensive research has highlighted impaired social cognitive functions in individuals with substance addiction. However, the specific deficit in social WM within this population remains notably understudied. Bridging this gap, we investigated social WM capacity using biological motion (BM) stimuli in methamphetamine (MA) abusers compared to an inmate control group, alongside contrasting these findings with their canonical WM deficits. Across two studies, we recruited female MA abusers (N = 80) undergoing post-isolation rehabilitation within a mandatory confinement circumstance. To ensure a pertinent comparison, we recruited female inmates (N = 80) subjected to comparable confinement. Results show substantial BM WM impairment in MA abusers, yet non-BM WM remains mostly intact. These findings highlight a pronounced social WM deficit in MA abusers, surpassing their canonical WM deficit relative to inmate controls. This suggests a distinct dissociation between social and canonical WM processing.

Stochastic quantisation of Yang–Mills–Higgs in 3D

We define a state space and a Markov process associated to the stochastic quantisation equation of Yang–Mills–Higgs (YMH) theories. The state space S\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathcal{S}$\\end{document} is a nonlinear metric space of distributions, elements of which can be used as initial conditions for the (deterministic and stochastic) YMH flow with good continuity properties. Using gauge covariance of the deterministic YMH flow, we extend gauge equivalence ∼ to S\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathcal{S}$\\end{document} and thus define a quotient space of “gauge orbits” O\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathfrak {O}$\\end{document}. We use the theory of regularity structures to prove local in time solutions to the renormalised stochastic YMH flow. Moreover, by leveraging symmetry arguments in the small noise limit, we show that there is a unique choice of renormalisation counterterms such that these solutions are gauge covariant in law. This allows us to define a canonical Markov process on O\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\\mathfrak {O}$\\end{document} (up to a potential finite time blow-up) associated to the stochastic YMH flow.

Wage Risk and Government and Spousal Insurance

Abstract The extent to which households can self-insure depends on family structure and wage risk. We calibrate a model of couples and singles’ savings and labour supply under two types of wage processes. The first wage process is the canonical—age-independent, linear—one that is typically used to evaluate government insurance provision. The second wage process is a flexible one. We use our model to evaluate the optimal mix of the two most common types of means-tested benefits—IW versus income floor. The canonical wage process underestimates wage persistence for women and thus implies that IW benefits should account for most benefit income. In contrast, the richer wage process that matches the wage data well, implies that the income floor should be the main benefit source, similarly to the system in place in the U.K. This stresses that allowing for rich wage dynamics is important to properly evaluate policy.

Transcriptomics analysis of the bovine endometrium during the perioestrus period.

During the oestrous cycle, the bovine endometrium undergoes morphological and functional changes, which are regulated by alterations in the levels of oestrogen and progesterone and consequent changes in gene expression. To clarify these changes before and after oestrus, RNA-seq was used to profile the transcriptome of oestrus-synchronized beef heifers. Endometrial samples were collected from 29 animals, which were slaughtered in six groups beginning 12 h after the withdrawal of intravaginal progesterone releasing devices until seven days post-oestrus onset (luteal phase). The groups represented proestrus, early oestrus, metoestrus and early dioestrus (luteal phase). Changes in gene expression were estimated relative to gene expression at oestrus. Ingenuity Pathway Analysis (IPA) was used to identify canonical pathways and functional processes of biological importance. A total of 5,845 differentially expressed genes (DEGs) were identified. The lowest number of DEGs was observed at the 12 h post-oestrus time point, whereas the greatest number was observed at Day 7 post-oestrus onset (luteal phase). A total of 2,748 DEGs at this time point did not overlap with any other time points. Prior to oestrus, Neurological disease and Organismal injury and abnormalities appeared among the top IPA diseases and functions categories, with upregulation of genes involved in neurogenesis. Lipid metabolism was upregulated before oestrus and downregulated at 48h post-oestrus, at which point an upregulation of immune-related pathways was observed. In contrast, in the luteal phase the Lipid metabolism and Small molecule biochemistry pathways were upregulated.

Unraveling the peculiarities and development of novel inhibitors of leishmanial arginyl-tRNA synthetase.

Aminoacylation by tRNA synthetase is a crucial part of protein synthesis and is widely recognized as a therapeutic target for drug development. Unlike the arginyl-tRNA synthetases (ArgRSs) reported previously, here, we report an ArgRS of Leishmania donovani (LdArgRS) that can follow the canonical two-step aminoacylation process. Since a previously uncharacterized insertion region is present within its catalytic domain, we implemented the splicing by overlap extension PCR (SOE-PCR) method to create a deletion mutant (ΔIns-LdArgRS) devoid of this region to investigate its function. Notably, the purified LdArgRS and ΔIns-LdArgRS exhibited different oligomeric states along with variations in their enzymatic activity. The full-length protein showed better catalytic efficiency than ΔIns-LdArgRS, and the insertion region was identified as the tRNA binding domain. In addition, a benzothiazolo-coumarin derivative (Comp-7j) possessing high pharmacokinetic properties was recognized as a competitive and more specific inhibitor of LdArgRS than its human counterpart. Removal of the insertion region altered the mode of inhibition for ΔIns-LdArgRS and caused a reduction in the inhibitor's binding affinity. Both purified proteins depicted variances in the secondary structural content upon ligand binding and thus, thermostability. Apart from the trypanosomatid-specific insertion and Rossmann fold motif, LdArgRS revealed typical structural characteristics of ArgRSs, and Comp-7j was found to bind within the ATP binding pocket. Furthermore, the placement of tRNAArg near the insertion region enhanced the stability and compactness of LdArgRS compared to other ligands. This study thus reports a unique ArgRS with respect to catalytic as well as structural properties, which can be considered a plausible drug target for the derivation of novel anti-leishmanial agents.

HIGHER‐ORDER INCOME RISK OVER THE BUSINESS CYCLE

AbstractWe explore the consequences of higher‐order risk in a standard incomplete‐markets life‐cycle model. We calibrate the model using a canonical income process with persistent and transitory risk, extended to feature cyclical shock distributions with left‐skewness and excess kurtosis. We estimate this income process for U.S. household data, and find shocks to be highly leptokurtic, with countercyclical variance and procyclical skewness of persistent shocks. In the model, first, higher‐order risk has sizable welfare implications; second, it matters quantitatively for the welfare costs of cyclical idiosyncratic risk; third, it has nontrivial implications for self‐insurance against shocks.

Reasons for a Total Simulation of Marital Consent in Judgements Pro Nullitate of the Metropolitan Tribunal in Kraków Passed Between 2010 and 2020

The article deals with the important element inherent in proving the invalidity of marriage on the grounds of total simulation of marital consent (Canon 1101 § 1), which is the reason for simulation. I analyse all the decisions pro nullitate matrimonii of the Metropolitan Tribunal in Kraków handed down in the years 2010-2020. In the first part, the importance of causa simulationis at the instruction stage in the canonical process is presented. The essential part of this study is devoted to causa celebrandi and causa simulandi occurring in the presented jurisprudence. I also propose some legal and pastoral measures that may help to eliminate instances of invalid marriages, concluding that the causa simulandi is an important aid for judges to achieve moral certitude about the nullity of a marriage for the reasons stated above.

A Reading of Friedrich A. Kittler’s Reading of E.T.A. Hoffmann’s “Der Goldene Topf” (The Golden Pot) in Aufschreibesysteme 1800/1900 (Discourse Networks 1800/1900)

Friedrich A. Kittler’s canonical Aufschreibesysteme 1800/1900 (Discourse Networks 1800/1900) threatened the very idea of the canonicity of German literature. Yet Kittler’s readings systematically dismiss, mishear, and distort foreign voices who resist and cannot easily fit into his rigid theoretical framework. This discursive strategy is most apparent in his formative reading of E.T.A. Hoffmann’s 1814 “Der Goldene Topf: Ein Märchen aus der neuen Zeit” (The Golden Pot: A Fairy Tale for the Modern Age). Despite its erasures and repressions of difference, his reading of this text has had a largely positive reception. A re-reading of his formative reading is thus long overdue. By closely analyzing Kittler’s interpretation of Hoffmann’s text, this article demonstrates that Kittler's expressed claim to challenge a canonical approach to German literature and his disruptions of disciplinary norms and behavioral conventions mask his fundamental affiliation with processes of canonization.

Sex differences in development of functional connections in the face processing network.

Understanding sex differences in typical development of the face processing network is important for elucidating disruptions during atypical development in sex-linked developmental disorders like autism spectrum disorder. Based on prior sex difference studies in other cognitive domains, this study examined whether females show increased integration of core and extended face regions with age for face viewing, while males would show increased segregation. This study used a cross-sectional design with typically developing children and adults (n=133) and a functional MRI face localizer task. Psychophysiological interaction (PPI) analysis examined functional connectivity between canonical and extended face processing network regions with age, with greater segregation indexed by decreased core-extended region connectivity with age and greater integration indexed by increased core-extended region connectivity with age. PPI analysis confirmed increased segregation for males-right fusiform face area (FFA) coupling to right inferior frontal gyrus (IFG) opercular when viewing faces and left amygdala when viewing objects decreased with age. Females showed increased integration with age (increased coupling of the right FFA to right IFG opercular region and right occipital face area [OFA] to right IFG orbital when viewing faces and objects, respectively) and increased segregation (decreased coupling with age of the right OFA with IFG opercular region when viewing faces). Development of core and extended face processing network connectivity follows sexually dimorphic paths. These differential changes mostly occur across childhood and adolescence, with males experiencing segregation and females both segregation and integration changes in connectivity.

Inclusion and Hegemony: Reading Salmān al-Fārisī's Conversion Story

In the otherwise expansive medieval Arabic literature, the scarcity of information concerning the conversion process of the early Islamic community piques interest in the handful of existing conversion narratives.One particular narrative that stands out is the conversion story of Salmān al-Farisi, recounting his transformation from a devout Zoroastrian to a dedicated companion of Prophet Muhammad. In the compilation of stories of Salmān al-Farisi by Louis Massignon named "Khabar Salmān," the persistence of many plot elements across different accounts of the story suggests a deliberate process of repetition and canonization. Recognizing the Salmān al-Farisi story as a site of memory, curation, and elite intentions, this paper considers the purpose of the story in forging Muslim identity, managing intergroup dynamics, and maintaining political power within the early Islamic community.

A Failed Canonization Process of Theological Knowledge in Contemporary Germany: An Analysis of the Practices of Ordinary Muslims

How do specific theological narratives and religious meanings prevail, fade, or become established? How do certain endeavors to canonize religious knowledge fail? How do the specific meanings individuals attribute to religious knowledge influence processes of negotiation and canonization? Drawing upon intensive ethnographic fieldwork, this article analyzes a particular negotiation of Islamic knowledge within a local jamaat of a German mosque association by taking seriously the practices of ordinary Muslims. It highlights the social dynamics of religious power and emphasizes the social embeddedness of theological meaning-making. In so doing, this article provides insights into the shaping of religious power and authority, and, in particular, into the complex process of successes and failures of attempts to canonize theological knowledge within the contemporary German-speaking Muslim landscape.