Zum Ursprung von Epistemischer Modalität, Evidentialität und Subjektivität in Verben des Denkens und Erkennens am Beispiel des Niederländischen

This paper aims to contribute to the debates about the nature of the speaker-related meanings of the mental state predicates, on the basis of a diachronic corpus study into the semantic evolution of five such verbs in Dutch. The analyses show that each of these verbs develops its own spe-cific profile in terms of a limited set of clearly distinguishable speaker-related meanings, viz. epistemic modality, evidentiality, and ‘subjectivi-ty’. Each of these meanings is moreover characterized by a distinctive di-achronic path. The study thus also demonstrates the independent status of ‘subjectivity’ as a meaning category.Diese Untersuchung hat zum Ziel, einen Beitrag zur Debatte über die Art der sprecherbezogenen Bedeutungen von Verben des Denkens und Erkennens zu leisten, indem sie versucht, mithilfe einer diachronischen Korpusstudie die Entwicklung von fünf solchen Verben in der niederländischen Sprache darzustellen. Forschungsresultate zeigen, dass jedes der untersuchten Verben ein eigenes Profil im Sinne einer begrenzten Reihe von untereinander deutlich unterscheidbaren sprecherbezogenen Bedeutungen entwickelt, nämlich epistemische Modalität, Evidentialität und Subjektivität. Jede dieser Bedeutungen ist außerdem durch einen distinktiven diachronischen Entwicklungsweg gekennzeichnet. Zusätzlich veranschaulicht die Untersuchung den selbstständigen Status der Subjektivität als Bedeutungskategorie

POIMANJE GRAMATIKE I UMA KAO SKUPA UZORAKA ODNOSNO PROCESA: KOGNITIVNO-FUNKCIONALNI PRISTUP

This paper focuses on one element dividing Cognitive Linguistics and more traditional functional linguistic approaches to grammar, viz. the contrast between the construction oriented approach predominating in the former and the rule or process oriented approach prevailing in the latter. It offers a ‘conceptual analysis’ of the issue, arguing (i) that a process concept of grammar is not misguided (pace suggestions to the contrary by some cognitive linguists) but needs to integrate certain insights from the constructional approach, and (ii) that in some version the two model types are largely compatible, reflecting different perspectives on the same phenomena.Rad se usredotočava na jedan element glede kojeg se kognitivna lingvistika i tradicionalni funkcionalni pristupi gramatici razilaze, tj. na opreku između pristupa koji naglasak stavlja na konstrukciju (što je znakovito za kognitivnu lingvistiku) i pristupa koji naglašava procese (što dominira u funkcionalnoj gramatici). Nudi se “konceptualna analiza” razlike i tvrdi: (i) da poimanje gramatike kao procesa ne vodi na stranputicu (unatoč suprotnim tvrdnjama nekih kognitivinih lingvista) pod uvjetom da se integriraju neka rješenja iz konstrukcijskog pristupa te (ii) da su u nekim svojim verzijama dva tipa modela uglavnom kompatibilna i da iste pojave prikazuju iz različitih perspektiva

Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor

The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R), the primary Ca2+-release channel in the endoplasmic reticulum (ER). Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4) has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP (3)R1 was related to the distinctive alpha-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG). By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced alpha-helicity, neither bound nor inhibited the IP (3)R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the alpha-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications

Stage shift and relative survival for head and neck cancer during the 2020 COVID-19 pandemic: a population-based study of temporal trends

ObjectiveDuring the first wave of the COVID-19 pandemic in 2020, non-essential health services were suspended in Belgium, and the public was ordered to socially isolate. Underdiagnosis of cancer during this period was reported worldwide. Certain risk factors for head and neck cancer (HNC) overlap with those for COVID-19 incidence and mortality, making underdiagnosis and subsequent stage shift of this potentially rapidly progressing cancer a major concern. We aimed to analyze incidence, clinical stage at presentation, and survival of patients diagnosed with HNC in 2020 in Belgium, considering recent temporal trends.MethodsUsing population-based data from the Belgian Cancer Registry (BCR), we extrapolated 2017-2019 trends in incidence, clinical stage, and 1-year relative survival (1yRS) of HNC to create an expected value for 2020 and compared this to the observed value.ResultsThere were 9.5% fewer HNCs diagnosed in 2020, compared to the predicted incidence. Underdiagnosis was larger for males (-11.8%), patients aged 50-64 (-11.2%) and 65-79 (-11.1%), and for oral cavity cancer (-17.6%). Shifts to more advanced stages were observed in larynx and oropharynx tumors and for (male) patients aged 80+. A 2.4 percentage point decline in 1yRS was observed, relative to the increasing trends in 1yRS (2017-2019).ConclusionThe COVID-19 pandemic led to underdiagnosis of HNC, resulting in shifts to more advanced stage at presentation in certain subgroups. A stage shift can be expected for the 9.5% of tumors not yet diagnosed at the end of 2020. HNC patients diagnosed in 2020 suffered higher than expected mortality

PET iterative reconstruction incorporating an efficient positron range correction method

Positron range is one of the main physical effects limiting the spatial resolution of positron emission tomography (PET) images. If positrons travel inside a magnetic field, for instance inside a nuclear magnetic resonance (MR) tomograph, the mean range will be smaller but still significant. In this investigation we examined a method to correct for the positron range effect in iterative image reconstruction by including tissue-specific kernels in the forward projection operation. The correction method was implemented within STIR library (Software for Tomographic Image Reconstruction). In order to obtain the positron annihilation distribution of various radioactive isotopes in water and lung tissue, simulations were performed with the Monte Carlo package GATE [Jan et al. 2004 [1]] simulating different magnetic field intensities (0 T, 3 T, 9.5 T and 11 T) along the axial scanner direction. The positron range kernels were obtained for 68Ga in water and lung tissue for 0 T and 3 T magnetic field voxellizing the annihilation coordinates into a three-dimensional matrix. The proposed method was evaluated using simulations of material-variant and material-invariant positron range corrections for the HYPERImage preclinical PET-MR scanner. The use of the correction resulted in sharper active region boundary definition, albeit with noise enhancement, and in the recovery of the true activity mean value of the hot regions. Moreover, in the case where a magnetic field is present, the correction accounts for the non-isotropy of the positron range effect, resulting in the recovery of resolution along the axial plane

Ethanol exposure increases mutation rate through error-prone polymerases

International audienceEthanol is a ubiquitous environmental stressor that is toxic to all lifeforms. Here, we use the model eukaryote Saccharomyces cerevisiae to show that exposure to sublethal ethanol concentrations causes DNA replication stress and an increased mutation rate. Specifically, we find that ethanol slows down replication and affects localization of Mrc1, a conserved protein that helps stabilize the replisome. In addition, ethanol exposure also results in the recruitment of error-prone DNA polymerases to the replication fork. Interestingly, preventing this recruitment through mutagenesis of the PCNA/Pol30 polymerase clamp or deleting specific error-prone polymerases abolishes the mutagenic effect of ethanol. Taken together, this suggests that the mutagenic effect depends on a complex mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases. Apart from providing a general mechanistic framework for the mutagenic effect of ethanol, our findings may also provide a route to better understand and prevent ethanol-associated carcinogenesis in higher eukaryotes

Discovering Argumentative Patterns in Energy Polylogues: A Macroscope for Argument Mining

A macroscope is proposed and tested here for the discovery of the unique argumentative footprint that characterizes how a collective (e.g., group, online community) manages differences and pursues disagreement through argument in a polylogue. The macroscope addresses broader analytic problems posed by various conceptualizations of large-scale argument, such as fields, spheres, communities, and institutions. The design incorporates a two-tier methodology for detecting argument patterns of the arguments performed in arguing by an interactive collective that produces views, or topographies, of the ways that issues are generated in the making and defending of standpoints. The design premises for the macroscope build on insights about argument patterns from pragma-dialectical theory by incorporating research and theory on disagreement management and the Argumentum Model of Topics. The design reconceptualizes prototypical and stereotypical argument patterns for characterizing large-scale argumentation. A prototype of the macroscope is tested on data drawn from six threads about oil-drilling and fracking from the subreddit Changemyview. The implementation suggests the efficacy of the macroscope’s design and potential for identifying what communities make controversial and how the disagreement space in a polylogue is managed through stereotypical argument patterns in terms of claims/premises, inferential relations, and presentational devices