Search

Abstract Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH) are major metabolic diseases with increasing global prevalence and no approved therapies. There is a mounting need to develop biomarkers of diagnosis, prognosis and treatment response that can effectively replace current requirements for liver biopsies, which are invasive, error-prone and expensive. We performed SomaLogic serum proteome profiling with baseline (n = 231) and on-treatment (n = 72, Weeks 12 and 16, Placebo and 25 mg PF-05221304) samples from a Phase 2a trial (NCT03248882) with Clesacostat (PF-05221304), an acetyl coA carboxylase inhibitor (ACCi) in patients with NAFLD/NASH. SomaSignal NASH probability scores and expression data for 7000+ analytes were analyzed to identify potential biomarkers associated with baseline clinical measures of NAFLD/NASH [Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] as well as biomarkers of treatment response to ACCi. SomaSignal NASH probability scores identified biopsy-proven/clinically defined NIT-based (Presumed) NASH classification of the cohort with > 70% agreement. Clesacostat-induced reduction in steatosis probability scores aligned with observed clinical reduction in hepatic steatosis based on MRI-PDFF. We identify a set of 69 analytes that robustly correlate with clinical measures of hepatic inflammation and steatosis (MRI-PDFF, ALT and AST), 27 of which were significantly reversed with ACC inhibition. Clesacostat treatment dramatically upregulated Wnt5a protein and Apolipoproteins C3 and E, with drug-induced changes significantly correlating to changes on MRI-PDFF. Our data demonstrate the utility of SomaLogic- analyte panel for diagnosis and treatment response in NAFLD/NASH and provide potential new mechanistic insights into liver steatosis reduction, inflammation and serum triglyceride elevation with ACC inhibition. (Clinical Trial Identifier: NCT03248882).

Kobus Marais’s monograph Translation Theory and Development Studies: A Complexity Theory Approach carves out new territory in translation studies, namely what might be called translational development studies – but it also seeks to fuse that new subdiscipline with an invigorated complexity- theoretical framework. This article seeks to promote and advance Marais’s project by offering correctives to two areas where his own theoretical framework remains somewhat blurry – in fact, undeveloped – namely the translator’s agency and social constructivism. The article explores an emergentist theory of “icosis” (somatic plausibilization) as a solution that, like Marais’s own approach, is steeped in Peircean semeiotic.

The sounds of birds form the outdoor playlist of our lives. Birds appeal to the public, in part because of the wide variety of interesting sounds they make. This popularity has led to a long history of amateur participation in ornithology, which has recently produced rapid increases in freely available online databases with hundreds of thousands of bird sounds recorded by birdwatchers. These databases provide unique opportunities for teachers to guide students through processes to learn to identify bird species by their sounds. The techniques we summarize here include combining the auditory components of recognizing different types of sounds birds make with visual components of reading sonograms, widely available visual representations of sounds.

Möbius semioticity: Six takes on Peeter Torop’s semiotics-of-culture model of textuality

This paper explores the creation of (a sense of) reality in Richard Powers’ 2006 novel The Echo Maker and Jean Baudrillard’s theory of simulacra, especially as that latter is applied by Kevin Casper to the 2010 movie Jackass 3D. The focus is on neurology, or perhaps neurophilosophy, rather than literary criticism or film studies, or even Baudrillard’s cultural theory: the various cultural texts are interrogated for what their explicit and implicit neurological theories can tell us about how we “realize” (organize, make real) our selves and/ in the world. Key in this process, the paper shows, are “fiction” for Powers (as it arises out of ubiquitous human “confabulation” as an attempt to impose coherence on the self and the world) and “simulacra” for Baudrillard; both become primary channels of social construction. The Capgras Delusion, which Powers places at the center of his novel, is especially useful in its tracking of the effects damage to our emotional circuits has on the creation of a sense of reality; Powers even seeks to universalize Capgras as a general human failure to accept the kinship of all living things, or what Arne Naess calls “the Self-realization of the ecological self.” This universalized deficit is close enough to Baudrillard’s (faux?-)apocalyptic conception of simulacra subsuming reality into virtuality in postmodernity to make it a useful test for Baudrillard’s jeremiads. Ultimately the paper moves in the direction of icosis as the somatic group plausibilization of normative opinion.

State-of-the-art centrifugal compressor units utilised in pipeline and in energy storage applications face the challenge of flexible and highly efficient operation. Geometric contouring on the hub side near a vaned diffuser affects the flow in a way which increases operational flexibility by delaying the incipience of instability and thereby increases compressor operating range. In the present paper, a hub-side wall contouring is applied within the vaneless space and the vaned diffuser of an open impeller centrifugal compressor stage. The performance characteristic of the novel hub contouring is evaluated in a scale-model test rig and compared against a baseline design. A stable operating range increase of 8% is achieved for the contoured design at Mu 2 = 1.16. 5-hole probe measurements covering a complete diffuser blade-to-blade passage are performed upstream the diffuser and compared both against CFD simulations and against the measurements of the baseline design for an operating point near the stability limit.

During cytokinesis, the cell employs various molecular machineries to separate into two daughters. Many signaling pathways are required to ensure temporal and spatial coordination of the molecular and mechanical events. Cells can also coordinate division with neighboring cells to maintain tissue integrity and flexibility. In this review, we focus on recent advances in the understanding of the molecular underpinnings of cytokinesis.

Drawing on Henri Meschonnic’s notion of an “inscient ethics,” and putting “inscience” into dialogue with the old ideal of a “science” of translation, the article explores the collective socio-affective ecologies that organize and regulate social and professional norms and values of translation below the level of conscious awareness—as the true underlying structure not only of “subjectivity” (somatics) but also of “objectivity” (“desomatized science”). Two models are developed for this dual structuring, the first circular or cyclical, with “objectification/desomatization” down one side and “subjectification/somatization” up the other; the other based on Gregory Bateson’s theorization of the double-bind, with both sides recursively intertwined. The circular model is developed in dialogue with Shoshana Felman; the double-bind model in dialogue with Juliane House’s model of Translation Quality Assessment. Both point us further to a retheorization of socio-affective ecologies in terms of ecosis/icosis.

The paper explores Henri Meschonnic’s conception of rhythm as a vehicle of subjectivization—but specifically of intersubjectization, and thus as a key channel of knowledge transfer or knowledge translation. Because we experience rhythm in time, knowledge-translation that comes to us as rhythm-as-intersubjectivization is experienced serially; because it is a phenomenology of body-becoming-mind, it is experienced kinesthetically-becoming-affectively-becoming-conatively, which is to say, in the model this paper develops, “icotically”—through the collective move toward the normativization of opinion as “truth” or “fact”. Key to knowledge-translation-as-rhythm is the ear, which is the icotic agent of the group in each individual, that which helps us hear style as truth. The first question for knowledge-translation, how many subjects it creates—one for each text (source and target)? one for each reader? one for each reading?—is superseded by the icotic take on subjectivization, which collectivizes it, meaning that the exact number is less important than the social entelechies in which subjects participate.

Este trabalho investiga a resposta "positiva" ou "utópica" à condição pós-colonial, desenvolvida por Tejaswini Niranjana em Siting Translation: uma tentativa de enquadrar a tradução a serviço da descolonização. Identifica um mito pós-colonial que parte do estágio pré-colonial, atravessa o passado colonial recente e a pós-colonialidade atual até atingir um futuro estágio imaginado de descolonização, de modo a contrastar as versões nacionalistas do mito, que enfatizam a pureza dos estados pré-colonial e descolonizado, com as versões pós-coloniais, que insistem que todos os quatro estados encontram-se combinados. Niranjana remonta à ‘Tarefa do Tradutor’, de Walter Benjamin, para explorar as formas pelas quais o ato de tradução, tal como a re-leitura e/ou a re-escrita da história, envolve a "citação" de palavras de um contexto para outro, permitindo que a tradução seja instrumentalizada pelos colonizadores para fins de subjugação colonial, mas também pelos sujeitos pós-coloniais, para promover a descolonização. Finalmente, o artigo contrapõe o literalismo benjaminiano de Niranjana como a melhor modalidade tradutória descolonizadora às diversas abordagens exploradas por Vicente Rafael em Contracting Colonialism.

Evening Grosbeak (Coccothraustes vespertinus) populations have been hypothesized to be in steep decline across North America. Data characterizing long-term changes are needed to quantify the magnitude of the declines. We surveyed grosbeaks at a spring migratory stop-over site in Corvallis, Oregon, USA, where birds gather annually during April and May to feast on elm (Ulmus spp.) seeds before departing to breeding sites. An estimate produced by a statistics professor in the 1970s indicated peak numbers were 150,000 to 250,000 birds. Our surveys in 2013–2015 found annually variable numbers, from a few hundred grosbeaks in the lowest year to less than five thousand birds in the highest year. If the original estimate is approximately true, Evening Grosbeak numbers have experienced dramatic declines, averaging −2.6%/year, over the last four decades. Our local observation of declines during spring aligns with declines documented in winter across North America by bird feeder studies and in summer by the Breeding Bird Survey. We explore potential explanations for the changes in population size, such as influences of spruce budworm outbreaks, disease, and decreased structural diversity of forests owing to harvest practices. We also consider the challenges of interpreting changes in abundance of species with exceptionally variable populations, especially if population fluctuations or cycles may have long periodicities. Finally, we call for additional planned surveys to track the numbers of this enigmatic and charismatic species.

Depredation of birds by domestic cats is hypothesized to be one of many significant sources of mortality leading to global bird declines. Direct observations are relatively rarely documented compared with large numbers of birds hypothesized to be killed or wounded by cats. We analyzed data from two wildlife rehabilitation centers located in Salem and Grants Pass, Oregon USA, to understand which species were most likely to interact with a cat, and the species traits associated with cat interactions and habitats (urban vs. rural) of rescued birds. Interaction with a cat was the second-most commonly reported cause of admission, representing 12.3% of 6345 admissions. Half to two-thirds of birds were rescued from cats in urban settings and were usually species foraging on or near the ground. Most species were admitted to rehabilitation centers in direct proportion to their regional abundance. An exception was the absence of common species weighing less than 70 g, which we conclude is an effect of sampling bias. We conclude that cats most often interact with regionally common near-ground-dwelling bird species in both urban and rural habitats. Wildlife rehabilitation centers can provide valuable sources of data for cat-bird interactions but potential sources of uncertainty and bias in their data need to be considered carefully.

The effects of forest degradation, fragmentation, and climate change occur over long time periods, yet relatively few data are available to evaluate the long-term effects of these disturbances on tropical species occurrence. Here, we quantified changes in occupancy of 50 bird species over 17 years on Barro Colorado Island (BCI), Panama, a model system for the long-term effects of habitat fragmentation. The historical data set (2002–2005) was based on point counts, whereas the contemporary data set (2018) was based on acoustic monitoring. For most species, there was no significant change in occupancy; however, the occupancy of four species (Tinamus major, Polioptila plumbea, Myiarchus tuberculifer, and Ceratopipra mentalis) increased significantly, and the occupancy of three species (Saltator grossus, Melanerpes pucherani, and Cyanoloxia cyanoides) decreased significantly. Forest age explained the majority of occupancy variation and affected the occupancy of more bird species than survey period or elevation. Approximately 50% of the species seem to favor old-growth forest, and 15 species (30%) had a significantly higher occupancy in old-growth forest sites. Elevation had no significant impact on the occupancy of the majority of bird species. Although BCI has been a protected reserve for approximately 100 years, land-use legacies (i.e., forest age) continue to influence bird distribution.