17 research outputs found
Constructional schemas in variation : modelling contrastive negation
This paper discusses constructional variation in the domain of contrastive negation in English, using data from the British National Corpus. Contrastive negation refers to constructs with two parts, one negative and the other affirmative, such that the affirmative offers an alternative to the negative in the frame in question (e.g. shaken, not stirred; not once but twice; I don't like it - I love it). The paper utilises multiple correspondence analysis to explore the degree of synonymy among the various constructional schemas of contrastive negation, finding that different schemas are associated with different semantic, pragmatic and extralinguistic contexts but also that certain schemas do not differ from each other in a significant way.Peer reviewe
Typology and usage : The case of negation
Peer reviewe
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetĀ® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetĀ® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Not just contrastive : Constructions with negated restrictives in English
When restrictive adverbs are negated, an additive reading is produced (e.g., not only). This is particularly common in correlative constructions with a corrective part optionally introduced by but (e.g., not just in England but also in Scotland), but can also appear in other syntactic contexts. This study investigates formal and functional variation in the use of the four most common variants of negated restrictives (not only, not just, not simply, and not merely) from the perspective of constructional and usage-based approaches to language. The study is based on a dataset of 1599 tokens, annotated for formal, functional, and extralinguistic variables, and is analyzed using hierarchical configural frequency analysis. The contrastive correlative construction not only X but (also) Y appears as the central grammatical context for negated restrictives in English. In addition to its high frequency, not only displays the least variability in both form and function, which suggests a high degree of conventionalization. The less frequent variants of negated restrictives have more diffuse usage profiles, suggesting they are less conventionalized and may be emergent constructions which have not yet conventionalized into stable parts of the language. Methodologically, the study suggests an alternative to modeling alternations, which enables the detection of different degrees of conventionalization and which avoids conceptualizing alternations as choices conditioned by independent variables.Peer reviewe
Analogian ja kontrastin ongelma kognitiivisessa kielitieteessƤ
Arvioitu teos
Karolina Krawczak, Barbara Lewandowska-Tomaszczyk & Marcin Grygiel (toim.): Analogy and contrast in language. Perspectives from cognitive linguistics. Human Cognitive Processing 73. Amsterdam: John Benjamins 2022. 442 s. isbn 978-90-272-1154-5
The RNA-binding protein Snd1/Tudor-SN regulates hypoxia-responsive gene expression
Abstract
Snd1 is an evolutionarily conserved RNA-binding protein implicated in several regulatory processes in gene expression including activation of transcription, mRNA splicing, and microRNA decay. Here, we have investigated the outcome of Snd1 gene deletion in the mouse. The knockout mice are viable showing no gross abnormalities apart from decreased fertility, organ and body size, and decreased number of myeloid cells concomitant with decreased expression of granule protein genes. Deletion of Snd1 affected the expression of relatively small number of genes in spleen and liver. However, mRNA expression changes in the knockout mouse liver showed high similarity to expression profile in adaptation to hypoxia. MicroRNA expression in liver showed upregulation of the hypoxia-induced microRNAs miR-96 and -182. Similar to Snd1 deletion, mimics of miR-96/182 enhanced hypoxia-responsive reporter activity. To further elucidate the function of SND1, BioID biotin proximity ligation assay was performed in HEK-293T cells to identify interacting proteins. Over 50% of the identified interactors were RNA-binding proteins, including stress granule proteins. Taken together, our results show that in normal growth conditions, Snd1 is not a critical factor for mRNA transcription in the mouse, and describe a function for Snd1 in hypoxia adaptation through negatively regulating hypoxia-related miRNAs and hypoxia-induced transcription consistent with a role as stress response regulator
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Prognostic Value of Early Phase 1H Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging in Comatose Survivors of Out-of-Hospital Cardiac Arrest - A Sub-Study of the Xe-Hypotheca Trial
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Prognostic Value of Early Phase 1H Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging in Comatose Survivors of Out-of-Hospital Cardiac Arrest - A Sub-Study of the Xe-Hypotheca Trial
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Comparison of the prognostic value of early-phase proton magnetic resonance spectroscopy and diffusion tensor imaging with serum neuron-specific enolase at 72 h in comatose survivors of out-of-hospital cardiac arrestāa substudy of the XeHypotheca trial
PurposeWe compared the predictive accuracy of early-phase brain diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS), and serum neuron-specific enolase (NSE) against the motor score and epileptic seizures (ES) for poor neurological outcome after out-of-hospital cardiac arrest (OHCA).MethodsThe predictive accuracy of DTI, 1H-MRS, and NSE along with motor score at 72 h and ES for the poor neurological outcome (modified Rankin Scale, mRS, 3ā-ā6) in 92 comatose OHCA patients at 6 months was assessed by area under the receiver operating characteristic curve (AUROC). Combined models of the variables were included as exploratory.ResultsThe predictive accuracy of fractional anisotropy (FA) of DTI (AUROC 0.73, 95% CI 0.62-0.84), total N-acetyl aspartate/total creatine (tNAA/tCr) of 1H-MRS (0.78 (0.68ā-ā0.88)), or NSE at 72 h (0.85 (0.76ā-ā0.93)) was not significantly better than motor score at 72 h (0.88 (95% CI 0.80-0.96)). The addition of FA and tNAA/tCr to a combination of NSE, motor score, and ES provided a small but statistically significant improvement in predictive accuracy (AUROC 0.92 (0.85-0.98) vs 0.98 (0.96-1.00), pā=ā0.037).ConclusionNone of the variables (FA, tNAA/tCr, ES, NSE at 72 h, and motor score at 72 h) differed significantly in predicting poor outcomes in this patient group. Early-phase quantitative neuroimaging provided a statistically significant improvement for the predictive value when combined with ES and motor score with or without NSE. However, in clinical practice, the additional value is small, and considering the costs and challenges of imaging in this patient group, early-phase DTI/MRS cannot be recommended for routine use.Trial registrationClinicalTrials.gov NCT00879892, April 13, 2009