Sheaf representations of MV-algebras and lattice-ordered abelian groups via duality

We study representations of MV-algebras -- equivalently, unital lattice-ordered abelian groups -- through the lens of Stone-Priestley duality, using canonical extensions as an essential tool. Specifically, the theory of canonical extensions implies that the (Stone-Priestley) dual spaces of MV-algebras carry the structure of topological partial commutative ordered semigroups. We use this structure to obtain two different decompositions of such spaces, one indexed over the prime MV-spectrum, the other over the maximal MV-spectrum. These decompositions yield sheaf representations of MV-algebras, using a new and purely duality-theoretic result that relates certain sheaf representations of distributive lattices to decompositions of their dual spaces. Importantly, the proofs of the MV-algebraic representation theorems that we obtain in this way are distinguished from the existing work on this topic by the following features: (1) we use only basic algebraic facts about MV-algebras; (2) we show that the two aforementioned sheaf representations are special cases of a common result, with potential for generalizations; and (3) we show that these results are strongly related to the structure of the Stone-Priestley duals of MV-algebras. In addition, using our analysis of these decompositions, we prove that MV-algebras with isomorphic underlying lattices have homeomorphic maximal MV-spectra. This result is an MV-algebraic generalization of a classical theorem by Kaplansky stating that two compact Hausdorff spaces are homeomorphic if, and only if, the lattices of continuous [0, 1]-valued functions on the spaces are isomorphic.Comment: 36 pages, 1 tabl

The role of the inflammasome in skin inflammatory diseases and its regulation in general processes of inflammation

Interleukin-1β (IL-1β) ist ein entzündungsförderndes Zytokin, welches eine Schlüsselrolle in akuten und chronischen Entzündungen spielt. Insbesondere seine Rolle in der Pathogenese der Autoinflammation machen IL-1β zu einem idealen Ziel um die schwere verschiedenartigster Erkrankungen schnell zu reduzieren. IL-1β wird in seiner biologisch inaktiven Pro-Form produziert und um aktiviert und sekretiert zu werden muss es durch einen Multiproteinkomplex, das sogenannte Inflammasom, geschnitten werden. Daher spielt die Aktivität des Inflammasoms eine wichtige Rolle in vielen pathologischen und physiologischen Prozessen. Der Hauptteil meiner Doktorarbeit befasst sich mit der Identifikation der Mechanismen, welche das Inflammasom regulieren könnten. Unter den verschiedenen zur Zeit bekannten Inflammasomen ist das am meisten studierte das NLRP3 Inflammasom. Es konnte gezeigt werden, dass viele verschiedene Stimulantien mit unterschiedlichen Eigenschaften (Umweltstress, pathogene Partikel, pathogen-assoziierte Strukturen, gefahr- induzierende Metabolite, gefahr-induzierende Strukturen) das NLRP3 Inflammasom aktivieren können. Daher muss der Zelle ein gemeinsamer Pfad zugrunde liegen, welcher die unterschiedlichen Stimuli in einen einzelnen Pfad bündelt, welcher wiederum zur Aktivierung des Inflammasoms führt. In der vorliegenden Arbeit konnten wir zeigen, das Mitogen-Associated Protein Kinasen (MAPKn) aktiviert werden nachdem Immun- und Nicht-Immunzellen verschiedensten Stimulatoren des Inflammasoms ausgesetzt wurden und das diese Stimulatoren beteiligt sind an der Schädigung der Mitochondrien und dem Auslaufen mitochondrialer DNA in das Zytosol, was im Anschluss zur Aktivierung des NLRP3 Inflammasoms führt. Dieser Prozess ist auf die zwei BCL-2 Familienmitglieder, BAD und BCL-XL angewiesen und wird durch MAPK und Phosphatase-1 abgestimmt. Acne vulgaris ist eine der am Häufigsten auftretenden Hauterkrankung welche Rund 80% der Bevölkerung irgendwann in ihrem Leben betrifft. Es ist eine multifaktorielle Erkrankung, welche das Potential in sich birgt sich in einer schweren Form zu manifestieren. In dieser Doktorarbeit zeigen wir, dass Propionibacterium acnes, ein Bakterium welches sich in entzündeten Aknelesionen (Pusteln) findet, fähig ist, nach Internalisierung, das NLRP3 Inflammasom zu aktivieren, was zur Freisetzung von cathepsin B-abhängigen reaktiven Sauerstoffradikalen führt. Wir konnten weiter zeigen, dass das NLRP3 Inflammasom in myeloiden Zellen eine wichtige Rolle in einem in vivo Modell spielt und dass das gezielte Ansteuern des IL-1β ein effektiver Ansatz ist neutrophile Entzündungsreaktionen zu hemmen. Kontakt-Überempfindlichkeit ist ebenfalls eine häufige Hauterkrankung in welcher IL-1β eine wichtige Rolle spielt. Kontaktallergene sind chemische kleine organische Moleküle welche an körpereigene Proteine binden und so ein Neo-Antigen generieren, in einem Prozess welcher als Haptenbildung bezeichnet wird. Haptene, wie Dinitrofluorobenzen (DNFB) und Dinitrothiocyanobenzen (DNTB) präsentieren kreuzreaktive Antigene, welche sensibilisierende oder tolerierende T-Zellantworten hervorrufen. In dieser Doktorarbeit konnten wir im Mausmodell zeigen, dass das NLRP3 Inflammasom zur Sensibilisierung gegen DNTB und zur Tolerierung von DNFB führen kann, was den ersten Beweis anführt, dass das Inflammasom eine Antigen-spezifische erworbene Immunantwort definieren kann und neue Strategien zur Beeinflussung von T-Zellantworten im Lebenden andeutet. Zusammenfassend geben die Ergebnisse dieser Doktorarbeit einen Einblick in die Regelung der Aktivierung des Inflammasoms und die daraus resultierende IL-1β Ausschüttung durch MAPKn und enträtseln die entscheidende Rolle des NLRP3 Inflammasoms in der Pathogenese der Acne vulgaris und der Entstehung der Kontakt-Überempfindlichkeit. Interleukin-1β (IL-1β) is a key pro-inflammatory cytokine associated to acute and chronic inflammation. It plays a crucial role in the pathogenesis of auto-inflammatory diseases and targeting IL-1β is an efficient way to obtain a sustained and rapid reduction in the severity of several disorders. IL-1β is synthetized in a pro-form, which is biologically inactive, and in order to become active and secreted needs to be cleaved by cytosolic multiprotein complexes called inflammasomes. Therefore, regulation of inflammasome activity is crucial in many pathological and physiological conditions. In the main part of this thesis, we looked for the possible mechanisms that could be responsible for the regulation of the inflammasome. Among the different inflammasomes known to date, the most studied one is NLRP3 inflammasome. Many different stimuli of different natures (environmental stresses, pathogen particles, pathogen-associated molecular patterns, metabolites considered as danger signals, danger-associated molecular patterns) have been shown to activate the NLRP3 inflammasome. Therefore its hypothesized that there may be a common pathway used by the cell to centralize such diverse stimuli to a unique pathway leading to inflammasome activation. In the present work, we could demonstrate that Mitogen- Associated Protein Kinases (MAPKs) become active upon stimulation of immune and non-immune cells with several inflammasome activators and that they are involved in mitochondria damage and leakage of mitochondrial DNA to the cytosol, subsequently activating the NLRP3 inflammasome. This process is dependent on two BCL-2 family members, namely BAD and BCL- XL and modulated by MAPK phosphatase-1. Acne vulgaris is the most common skin disease, affecting around 80% of the population at some time in their lives. It is a multifactorial inflammatory disease, which can potentially manifest in very severe forms. In this thesis, wehow that Propionibacterium acnes (P.acnes), a bacterium found in inflammatory acne lesions (pustules), is able to activate the NLRP3 inflammasome upon its internalization, leading to reactive oxygen species generation and depending on cathepsin B. We could also show that NRLP3 inflammasome in myeloid cells plays a key role in an in vivo model, and that targeting IL-1β is an effective approach to prevent neutrophilic inflammation induced by P.acnes. Contact hypersensitivity is also a common skin disorder in which IL-1β was shown to play a role. Contact allergens are chemically reactive small organic molecules binding to self-proteins to generate immunogenic neo- antigens, through a process termed haptenization. Haptens such as dinitrofluorobenzene (DNFB) and dinitrothiocyanobenzene (DNTB) provide cross-reactive antigens driving opposite, sensitizing versus tolerizing, T cell responses. In this thesis we show that, in mice, the NLRP3 inflammasome can turn DNTB into a sensitizer and DNFB into a tolerizer, providing the first evidence that the inflammasome can define the type of adaptive immune response elicited by an antigen, and hint at new strategies to modulate T cell responses in vivo. Taken together, the results of this thesis provide insight to the regulation of inflammasome activation and subsequent IL-1β secretion by MAPK, they also unravel the crucial role of the NLRP3 inflammasome in the pathogenesis of Acne and in the process of sensitization of molecules in Contact Hypersensitivity

Dermoscopy of Pitted Keratolysis

Irritated hyperhidrotic soles with multiple small pits are pathognomonic for pitted keratolysis (PK). Here we show the dermatoscopic view of typical pits that can ensure the diagnosis. PK is a plantar infection caused by Gram-positive bacteria, particularly Corynebacterium. Increases in skin surface pH, hyperhidrosis, and prolonged occlusion allow these bacteria to proliferate. The diagnosis is fundamentally clinical and treatment generally consists of a combination of hygienic measures, correcting plantar hyperhidrosis and topical antimicrobials

Tendencias de la producción científica en salud general y salud pública de autores afiliados a instituciones brasileñas en publicaciones de alto impacto y del SciELO : 1995-2019

This study aimed to assess the percentage of articles with authors affiliated to Brazilian institutions in high-impact journals and SciELO journals and to evaluate trends in 5-year citations according to the author's affiliation and journal category. Bibliometric data were obtained using Scopus database from 1995 to 2019. Publications were selected from four journal categories: High-impact General Health (HGH), High-impact Public Health (HPH), SciELO General Health (SGH) and SciELO Public Health (SPH). The number of citations that were received five years after publication and the percentage of publications with any author affiliated to Brazil were calculated by each year. The same 146 journals were followed. There was a significant increase in percentage of articles with authors affiliated to Brazilian institutions in all sets of journals. Among HGH, there was an increasing from 0.3% to 1.5% between 1995-2019, for HPH from 1% to 3%, for SGH from 49.7% to 55.4%, and for SPH from 47.4% to 71.9%. There was a significant (p < 0.01) increase in the mean of 5-year citations in all groups and Brazilian affiliated articles increased more than average. For each 10 years, average HGH articles increased 11.9 citations and Brazilian affiliated articles 32.0 citations. The results suggest that the presence of Brazilian science is increasing, and the scientific impact has increased more than average.O estudo buscou avaliar o percentual de artigos por autores filiados a instituições brasileiras em revistas de alto impacto e do SciELO, além de avaliar as tendências em citações ao longo de cinco anos, de acordo com a filiação do autor e a categoria do periódico. Foram obtidos dados bibliométricos com o uso da base de dados Scopus entre 1995 e 2019. As publicações foram selecionadas em quatro categorias: Saúde Geral com Alto Impacto (SGAP), Saúde Pública com Alto Impacto (SGAP), Saúde Geral no SciELO (SGS) e Saúde Pública no SciELO (SPS). Foi calculado por ano, o número de citações recebidas em cinco anos a partir da publicação e o percentual de publicações com qualquer dos autores filiado a uma instituição brasileira. As mesmas 146 revistas foram acompanhadas. Em todas as categorias de revistas, houve um aumento significativo no percentual de artigos com autores filiados a instituições brasileiras. No SGAP, houve um amento de 0,3% para 1,5% entre 1995 e 2019, no SPAP de 1% para 3%, no SGS de 49,7% para 55,4% e no SPS de 47,4% para 71,9%. Houve um aumento significativo (p < 0,01) na média de citações em cinco anos em todos os grupos, e os artigos com filiação brasileira aumentaram mais que a média. Para cada 10 anos, a média de artigos SGAP aumentou em 11,9 citações e de artigos com filiação brasileira em 32,0 citações. Os resultados sugerem que a presença da ciência brasileira está aumentando, e que o impacto científico aumentou acima da média.Este estudio tuvo como objetivo evaluar el porcentaje de artículos con autores afiliados a instituciones brasileñas en publicaciones de alto impacto y en SciELO, así como para evaluar tendencias en citas durante cinco años, según la afiliación del autor y categoría de la publicación. Los datos bibliométricos se obtuvieron usando la base de datos Scopus desde 1995 a 2019. Las publicaciones fueron seleccionadas de cuatro categorías: Alto Impacto General en Salud (HGH por sus siglas en inglés), Alto Impacto Público en Salud (HPH), SciELO Salud General (SGH) y SciELO Salud Pública (SPH). El número de citas recibidas tras cinco años después de la publicación, y el porcentaje de publicaciones con cualquier autor afiliado a Brasil, se calcularon cada año. Se siguieron las mismas 146 publicaciones. Hubo un significativo incremento en el porcentaje de artículos con autores afiliados a instituciones brasileñas en todos los conjuntos de publicaciones. Entre HGH hubo un aumento del 0,3% al 1,5% entre 1995-2019, en HPH del 1% al 3%, en SGH desde el 49,7% al 55,4%, y en SPH del 47,4% al 71,9%. Hubo un significativo (p < 0,01) aumento en la media de las citas durante cinco años en todos los grupos y los artículos de afiliados brasileños se incrementaron más que el promedio. Por cada 10 años, el promedio de artículos HGH se incrementó en 11,9 citas y las citas de artículos de afiliados brasileños en 32,0 citas. Los resultados sugieren que se está incrementando la presencia de la ciencia brasileña y el impacto científico ha crecido más que la media

Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms

Nanotechnology has rapidly entered into human society, revolutionized many areas, including technology, medicine and cosmetics. This progress is due to the many valuable and unique properties that nanomaterials possess. In turn, these properties might become an issue of concern when considering potentially uncontrolled release to the environment. The rapid development of new nanomaterials thus raises questions about their impact on the environment and human health. This review focuses on the potential of nanomaterials to cause genotoxicity and summarizes recent genotoxicity studies on metal oxide/silica nanomaterials. Though the number of genotoxicity studies on metal oxide/silica nanomaterials is still limited, this endpoint has recently received more attention for nanomaterials, and the number of related publications has increased. An analysis of these peer reviewed publications over nearly two decades shows that the test most employed to evaluate the genotoxicity of these nanomaterials is the comet assay, followed by micronucleus, Ames and chromosome aberration tests. Based on the data studied, we concluded that in the majority of the publications analysed in this review, the metal oxide (or silica) nanoparticles of the same core chemical composition did not show different genotoxicity study calls (i.e. positive or negative) in the same test, although some results are inconsistent and need to be confirmed by additional experiments. Where the results are conflicting, it may be due to the following reasons: (1) variation in size of the nanoparticles; (2) variations in size distribution; (3) various purities of nanomaterials; (4) variation in surface areas for nanomaterials with the same average size; (5) differences in coatings; (6) differences in crystal structures of the same types of nanomaterials; (7) differences in size of aggregates in solution/media; (8) differences in assays; (9) different concentrations of nanomaterials in assay tests. Indeed, due to the observed inconsistencies in the recent literature and the lack of adherence to appropriate, standardized test methods, reliable genotoxicity assessment of nanomaterials is still challenging

Query Processing in Sensor Networks

sensors are small wireless computing devices that sense information such as light and humidity at extremely high resolutions. A smart sensor query-processing architecture using database technology can facilitate deployment of sensor networks. Recent advances in computing technology have led to the production of a new class of computing devices: the wireless, battery-powered, smart sensor. Traditional sensors deployed throughout buildings, labs, and equipment are passive devices that simply modulate a voltage on the basis of some environmental parameter. These new sensors are active, full-fledged computers, capable of not only sampling real-world phenomena but also filtering, sharing, and combinin

The prevalence rates and sequelae of delirium at age older than 90 years

Objective Although age and pre-existent dementia are robust risk factors for developing delirium, evidence for patients older than 90 years is lacking. Therefore, this study assesses the delirium prevalence rates and sequelae in this age group. Method Based on a Diagnostic and Statistical Manual (DSM)-5, Delirium Observation screening scale (DOS), and Intensive Care Delirium Screening Checklist (ICDSC) construct, in this prospective cohort study, the prevalence rates and sequelae of delirium were determined in 428 patients older than 90 years by simple logistic regressions and corresponding odds ratios (ORs). Results The overall prevalence delirium rate was 45.2%, with a wide range depending upon specialty: intermediate and intensive care services (83.1%), plastic surgery and palliative care (75%), neurology (72%), internal medicine (69%) vs. dermatology (26.5%), and angiology (14.5%). Delirium occurred irrespective of age and gender; however, pre-existent dementia was the strongest delirium predictor (OR 36.05). Delirious patients were less commonly admitted from home (OR 0.47) than from assisted living (OR 2.24), indicating functional impairment. These patients were more severely ill, as indicated by emergency (OR 3.25) vs. elective admission (OR 0.3), requirement for intensive care management (OR 2.12) and ventilation (OR 5.56–8.33). At discharge, one-third did not return home (OR 0.22) and almost half were transferred to assisted living (OR 2.63), or deceased (OR 47.76). Significance of results At age older than 90 years, the prevalence and sequelae of delirium are substantial. In particular, functional impairment and pre-existent dementia predicted delirium and subsequently, the loss of independence and death were imminent

Epidermal IL-15Rα acts as an endogenous antagonist of psoriasiform inflammation in mouse and man

Stromal cells at epithelial surfaces contribute to innate immunity by sensing environmental danger signals and producing proinflammatory cytokines. However, the role of stromal cells in controlling local inflammation is unknown. We show that endogenous soluble IL-15 receptor α (IL-15Rα) derived from epidermal stroma, notably keratinocytes, protects against dendritic cell/IL-15-mediated, T cell-driven skin inflammation in vivo, and is relevant to human psoriasis. Selective lack of IL-15Rα on stromal epidermal cells exacerbated psoriasiform inflammation in animals. Epidermal IL-15Rα was shed by keratinocytes via proteolytic cleavage by matrix metalloproteinases upon stimulation with proinflammatory cytokines to counteract IL-15-induced proliferation of IL-17(+) αβ and γδ T cells and production of TNF, IL-23, IL-17, and IL-22 during skin inflammation. Notably, administration of soluble IL-15Rα was able to repress secretion of IL-1β, IL-6, and TNF by keratinocytes, dampen expansion of IL-17(+) αβ and γδ T cells in vivo, and prevent psoriasis in two mouse models, including human xenograft AGR mice. Serum levels of soluble IL-15Rα negatively correlated with disease severity, and levels rose upon successful treatment of psoriasis in patients. Thus, stressed epidermal stromal cells use soluble IL-15Rα to dampen chronic inflammatory skin disease

Priestley duality for MV-algebras and beyond

We provide a new perspective on extended Priestley duality for a large class of distributive lattices equipped with binary double quasioperators. Under this approach, non-lattice binary operations are each presented as a pair of partial binary operations on dual spaces. In this enriched environment, equational conditions on the algebraic side of the duality may more often be rendered as first-order conditions on dual spaces. In particular, we specialize our general results to the variety of MV-algebras, obtaining a duality for these in which the equations axiomatizing MV-algebras are dualized as first-order conditions