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The Urdu/Hindi perfective-based future
No full textWe explore the emergence of the Modern Urdu/Hindi -g- future, which is built historically from a combination of an imperfective-marked main verb and perfective-marked motion verb ‘go’. Given that both verbs are members of the finite tense/aspect subsystem in the linguistic system in which the construction is innovated, we suggest that this construction starts out as a combination of clauses which pragmatically gives rise to a teleological inference. It is this inference that, under certain assumptions, generates future reference.publishe
The phosphatase PPM1F, a negative regulator of integrin activity, is essential for embryonic development and controls tumor cell invasion
No full textBackground: The Mn2+/Mg2+-dependent Ser/Thr phosphatase PPM1F was identified to control integrin activity. Furthermore, PPM1F regulates several protein kinases known to be involved in organizing the cytoskeleton and other cellular functions. Therefore, PPM1F appears critical for a multitude of physiological processes.
Results: Here, we report the phenotype of ppm1f gene disruption in mice. While heterozygous ppm1f ± mice are viable and fertile, ppm1f-/- mice show severe defects and significant morphological abnormalities in the developing brain and vasculature and abort embryonic development at day E10.5. Isolated ppm1f-/- MEFs or PPM1F-depleted human neuro-epithelial cells display enhanced integrin-dependent cell adhesion, deregulated PAK phosphorylation, and perturbed cell migration. These phenotypes were reversed by re-expression of the wildtype enzyme, but not the phosphatase-inactive PPM1F. In different human tumor cell types, PPM1F expression levels directly correlated with invasive potential, while deletion of PPM1F abrogates tissue invasion.
Conclusions: These results highlight the non-redundant role of this enzyme in integrin and PAK regulation and identify PPM1F as a promising target to limit tumor metastasis.publishe
Rethinking sustainable food supply chains: The role of stakeholders' place identity
No full textpublishe
Development and initial validation of a yes/no vocabulary test for North Sámi : Drawing on item response theory and signal detection theory
No full textThis paper accounts for the development and initial validation of a yes/no vocabulary test of North Sámi called North Sámi Vocabulary Test (NSVT). North Sámi (NS) is an Indigenous language spoken in northern Scandinavia. Being an endangered language, NS is in need of revitalisation efforts. One contribution is the provision of proficiency assessment tools. We administered a 75-item NSVT version (50 real verbs and 25 pseudoverbs) to users of North Sámi in Sweden and Norway (N = 289). Evidence of high item- and person-based reliability and separation indices were observed, as well as support for a number of validity facets. High correlations existed between NSVT scores and self-reported and rated spoken proficiency. The NSVT provides quick and reliable assessment of vocabulary knowledge and an indication of overall language proficiency in North Sámi.publishe
Highway systems : How good are they, really?
No full textHighways play a crucial role in transportation services as they facilitate long-distance traveling and allow driving at an almost constant speed, thus resulting in lower fuel consumption and emissions. Many existing highway systems were designed before practical computational tools had been developed. Furthermore, most existing approaches to evaluating highways focus on analyzing mobility data rather than studying the design of the highway system. To address this gap in existing research, in this paper, we investigate the problem of evaluating the efficacy of the design of real-world highway systems. To this end, we propose two novel measures for the effectiveness of highway systems, along with both exact and heuristic algorithms to compute them. In addition, we present a first-cut heuristic algorithm that aims to compute a highway system that optimizes our proposed measures. In our experiments, we demonstrate the potential of our methods in measuring the efficacy of real-world highway systems. We also evaluate the performance of our heuristic algorithm in computing a rough design of an efficient highway system.publishe
Mathematical modelling reveals compound-specific stress pathway activity
No full textDrug-induced liver injury (DILI) is a major problem for the drug development industry. It has been suggested that activation of stress pathways within cells is an important indicator of DILI. In this project, we aimed to develop a mathematical model of invoked stress responses by three compounds with high DILI liability: nitrofurantoin, diclofenac and ketoconazole. To this end, we used imaging data from HepG2 cells and cell-associated compound and intracellular glutathione measurements. We initially developed a model for the integrated and oxidative stress responses following nitrofurantoin exposure. Subsequently, we expanded this to simulate responses to diclofenac and ketoconazole. To apply the model to these compounds multiple parameters required recalibration, yet the structure of the model was unchanged. Our analysis shows that the magnitude of interactions between transcription factors and downstream targets can differ even when the activated pathways are the same.publishe
No ellipsis-contained antecedents : adjunct-licensed ellipsis in Spanish
No full textWhile implicitly assumed, the restriction that the antecedent of ellipsis cannot be base-merged within the ellipsis site has not to our knowledge been explicitly stated or analysed. In this article we discuss a pattern of ellipsis in Spanish, resembling gapping but we argue distinct from it, where ellipsis in the main clause can find its antecedent in some but not all adverbial clauses. The adverbial clauses that cannot provide the antecedent for ellipsis are, we argue, those that would have to be interpreted within the ellipsis site at LF. We argue that this pattern and its restrictions supports LF-identity theories of clausal ellipsis, and also provides evidence that remnants of clausal ellipsis move at LF.publishe
Sulfoquinovose is exclusively metabolized by the gut microbiota and degraded differently in mice and humans
No full textBackground:
Sulfoquinovose (SQ) is a green-diet-derived sulfonated glucose and a selective substrate for a limited number of human gut bacteria. Complete anaerobic SQ degradation via interspecies metabolite transfer to sulfonate-respiring bacteria produces hydrogen sulfide, which has dose- and context-dependent health effects. Here, we studied potential SQ degradation by the mammalian host and the impact of SQ supplementation on human and murine gut microbiota diversity and metabolism.
Results:
13CO2 breath tests with germ-free C57BL/6 mice gavaged with 13C-SQ were negative. Also, SQ was not degraded by human intestinal cells in vitro, indicating that SQ is not directly metabolized by mice and humans. Addition of increasing SQ concentrations to human fecal microcosms revealed dose-dependent responses of the microbiota and corroborated the relevance of Agathobacter rectalis and Bilophila wadsworthia in cooperative degradation of SQ to hydrogen sulfide via interspecies transfer of 2,3-dihydroxy-1-propanesulfonate (DHPS). Similar to the human gut microbiome, the genetic capacity for SQ or DHPS degradation is sparsely distributed among bacterial species in the gut of conventional laboratory mice. Escherichia coli and Enterocloster clostridioformis were identified as primary SQ degraders in the mouse gut. SQ and DHPS supplementation experiments with conventional laboratory mice and their intestinal contents showed that SQ was incompletely catabolized to DHPS. Although some E. clostridioformis genomes encode an extended sulfoglycolytic pathway for both SQ and DHPS fermentation, SQ was only degraded to DHPS by a mouse-derived E. clostridioformis strain.
Conclusions:
Our findings suggest that SQ is solely a nutrient for the gut microbiota and not for mice and humans, emphasizing its potential as a prebiotic. SQ degradation by the microbiota of conventional laboratory mice differs from the human gut microbiota by absence of DHPS degradation activity. Hence, the microbiota of conventional laboratory mice does not fully represent the SQ metabolism in humans, indicating the need for alternative model systems to assess the impact of SQ on human health. This study advances our understanding of how individual dietary compounds shape the microbial community structure and metabolism in the gut and thereby potentially influence host health.publishe
Evolutionary deconstrcution of C. elegans aggregation behaviour : environmental and genetic correlates of aggregation behaviour and its individual and interaction components
No full textStudies of animal behaviour have increasingly expanded its focus towards the evolutionary
explanations behind various behaviours. Albeit the challenges in conceptualisation, some
evolutionary models have successfully inferred the ontogeny or potential adaptations of
behaviours in different animal systems. Studies on collective behaviour have yet more
challenges to overcome due to increased dimensionality in the system. Even though the
endeavors have been facing difficulties in precisely quantifying and representing the
complexity of the collectives, recent developments in technologies have advanced the field
greatly. With the advanced tracking and imaging technologies and theoretical tools on
evolution, studying animal collective behaviour from an evolutionary perspective is becoming
more tractable.
In an attempt to contribute to such efforts, my thesis focused on investigating the
evolutionary explanations of the natural variation in aggregation behaviour across the wild
populations of C. elegans nematodes, a famous model organism in the field of biology. This
species has a rich database and resources on natural diversity and genomic information as
well as a well-characterised behaviour repertoires. With abundant resources and conceptual
knowledge readily available to this species, I asked if the aggregation behaviour in this
species naturally diverged in the wild populations, and if the variation pattern could suggest
a potential adaptation to different environments via natural genetic variations.
Chapter 1 has investigated this possibility in a small selected set of genetically divergent
strains isolated from various natural habitats of the globe. Aggregation behaviour assay was
conducted on this set of strains, and sensitive measures that can quantify the natural
variation and the dynamics of the behaviour were developed. High levels of variation were
revealed in the aggregation traits among the strains, and moreover, the behavioural variation
was found to be correlated with environmental categories and genetically inheritable. This
suggested that aggregation behaviour in C. elegans could have diverged in the wild, and
supported in expanding the results to broader global samples in Chapter 3.
Chapter 2 has developed from the result of Chapter 1, and focused on the potential
connection between aggregation and individual foraging behaviour in C. elegans. Since the
environmental categories of Chapter 1 were postulated to affect the foraging behaviour of C.
elegans, high levels of association was speculated between these collective and individual
behaviours. Individual foraging assays using the same divergent set of strains were
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conducted and foraging-related locomotive features were quantified. Using the Gaussian
Hidden Markov Model, the dwelling probabilities of different strains were estimated, and it
was revealed that the variation pattern of individual dwelling explains a big portion of the
natural variation in collective aggregation behaviour. This led to a possibility that aggregation
in C. elegans could be a self-organised foraging behaviour, and allowed the conceptual
decomposition of aggregation into three organisational levels of collective, inter-individual,
and individual components.
Chapter 3 culminates with the expanded analyses onto 185 global wild strains, investigating
the associations between the natural variation in aggregation behavioural components and
the specific environmental and genetic correlates. Generalised Least Squares model
revealed environmental associations to elevation and possibly to temperature fluctuations.
Genome Wide Association analyses found correlations to genetic loci involved in the
neuronal processes and foraging modulations in C. elegans. These results support the
conjectures that natural variation in C. elegans aggregation behaviour may reflect potential
divergence in animal’s adaptation in foraging behaviour and oxygen preferences.
With caveats and limitations in mind, I was able to not only quantitatively measure C.
elegans aggregation with precision in the laboratory, but also revealed its various associative
genetic and environmental factors. Through this project I hope to provide a study system for
collective behaviour and contribute to our understanding of evolution of animal collective
behaviour.publishe
Temperature-jump QCL spectroscopy of peptide dynamics : expanding spectral accessibility by dual-combs
No full textCombining infrared dual-comb spectroscopy with laser-induced nanosecond temperature-jumps enables fast tracking of peptide folding dynamics. Compared to single-wavenumber quantum cascade lasers, this method provides broader spectral information. Using a model peptide system, the study opens new perspectives for applying time-resolved IR spectroscopy to explore mechanistic details in biomolecular dynamics.publishe