Mediamusic (E-Journal)
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Computer programming skills: A cognitive perspective
The studies in the current thesis examine programming skills from a broad cognitive perspective. Study 1 aims to validate two short versions of an existing programming test. Studies 2 and 3 ask whether cognitive skills and autistic traits predict programming performance in an undergraduate course. The results show that logical reasoning is the most reliable predictor of programming skill and that autistic traits do not predict programming performance. In the final study, brain activity is measured in an EEG experiment. The results show that a programming language may be processed similarly in the brain to natural languages
Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families
Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.</p
The Pluriversity for Stuck Humxns:A Queer EcoPedagogy & Decolonial School
The Pluriversity for stuck humxns is an exploratory dialogue between early career researchers and established researchers. It responds to the concern that dominant forms of knowledge production are not assisting us to move towards life affirming ways of being and that alternatives are possible. The production of this chapter is one of many new acts towards realising other modes of being and becoming unstuck in scholar activist practice. The chapter begins with an invitation in the form of a poem by Lena Weber, and the resulting text is a response to the poem from multiple contributors from around the world, who imagine transgressive and progressive ‘departments’ of the Pluriversity. Situated amongst the impulses of queer ecopedagogy and drawing on imagination to understand and play with multiple (or diverse) knowledges, the authors explore what nurturing institutions for scholarly training and life may look like, and what might be possible and in fact are possible through our collaborative experience in the act of creating the Pluriversity for stuck humxns. Itself an intersectional being, this chapter is a queer inquiry dedicated to challenging and reframing norms and dogma and to shake up the boundaries of categories and narrowly and often dogmatically employed concepts. The authors break open pedagogy in ways that allowed them to question research practice and instead conceive of a ‘research worthy of their longing’
Developing Bacillus subtilis as a versatile bioproduct platform for agricultural and pharmaceutical applications
Bioproducts made by microbial cell factories play important roles in human life ranging from food, feed, cosmetic and pharmaceutical manufacturing. Microbial hosts are required to be non-pathogenic overproducers and should be growing at low costs. Bacillus subtilis is one of the bacteria, which can fulfill these requirements. It is generally regarded as safe, easy to modify genetically and able to grow fast in simple medium. It can secrete high levels of proteins into the culture medium, and has also been reported to be a high isoprene producer. The work described in the thesis of Yafeng Song focuses on two aspects. Firstly, she engineered B. subtilis to secrete high level of β-mannanase, a major mannan-degrading enzyme that is extensively used in agriculture as feed additive. This was achieved by increasing β-mannanase synthesis levels and enhancing protein secretion capacity. Secondly, she engineered B. subtilis to produce high levels of squalene and amorphadiene. Squalene is a critical precursor of many bioactive triterpenoids, and itself can also be applied as a pharmaceutical. Biosynthesis of squalene and its production improvement in B. subtilis was realized mainly by screening suitable squalene synthases, and increasing precursor supply. Amorphadiene is the key intermediate of the antimalarial drug artemisinin. Its production was elevated by systematically engineering the precursor supply pathway, competitive pathways, terpene synthase and a central metabolic pathway of B. subtilis. Overall, studies in this thesis demonstrated the potential of B. subtilis as a versatile bioproduct platform and provide universal strategies to engineer B. subtilis for industrial applications
The long-term genetic stability and individual specificity of the human gut microbiome
By following up the gut microbiome, 51 human phenotypes and plasma levels of 1,183 metabolites in 338 individuals after 4 years, we characterize microbial stability and variation in relation to host physiology. Using these individual-specific and temporally stable microbial profiles, including bacterial SNPs and structural variations, we develop a microbial fingerprinting method that shows up to 85% accuracy in classifying meta-genomic samples taken 4 years apart. Application of our fingerprinting method to the independent HMP cohort results in 95% accuracy for samples taken 1 year apart. We further observe temporal changes in the abundance of multiple bacterial species, metabolic pathways, and structural variation, as well as strain replacement. We report 190 longitudinal microbial associations with host phenotypes and 519 associations with plasma metabolites. These associations are enriched for cardiometabolic traits, vitamin B, and uremic toxins. Finally, mediation analysis suggests that the gut microbiome may influence cardiometabolic health through its metabolites.</p
Assembling Arctic Lifeways:a relational approach to lithic assemblages from the Greenlandic Dorset period
Portable, composite tool kits have been essential to the prehistoric dispersals of people around the globe. Nowhere is this clearer than during Greenlandic prehistory. Archaeological studies of tool kits have been vital to our understanding of this unique area and period in human history. The present thesis proceeds from the recent culture-historical definition of the Greenlandic Dorset (ca. 800 – 200 cal. BC), a Paleo-Inuit tradition that branched off into Greenland from the Canadian Early Dorset. This was achieved by the construction of a standardised taxonomy of its tradition for producing lithic components, using the chaîne opératoire methodology. This provided a rigorous means to assign lithic artefacts – the dominant remains from the period – within a coherent chapter of eastern Arctic prehistory. As such, the definition of the Greenlandic Dorset erased the separation between the Independence II and Dorset 1 of northernmost and western Greenland respectively. However, interpretations on the Arctic lifeways of the period have become equally standardised. With circular logic, the taxonomy itself has based interpretations of social behaviour within the period as highly conservative. To address this issue, the present thesis contributes as follows: 1) Demonstrate that relational thinking is a useful framework for researching how technologies structured Arctic lifeways; 3) Showcasing how a Relational Approach can help us reach relational perspectives on Arctic lifeways through bottom-up lithic study; 3) A comprehensive case-study that offers a novel understanding of how people and tool kits co-created a unique period in Arctic prehistory
Photophysics of First-Generation Photomolecular Motors:Resolving Roles of Temperature, Friction, and Medium Polarity
Light-driven unidirectional molecular rotary motors have the potential to power molecular machines. Consequently, optimizing their speed and efficiency is an important objective. Here, we investigate factors controlling the photochemical yield of the prototypical unidirectional rotary motor, a sterically overcrowded alkene, through detailed investigation of its excited-state dynamics. An isoviscosity analysis of the ultrafast fluorescence decay data resolves friction from barrier effects and reveals a 3.4 ± 0.5 kJ mol-1 barrier to excited-state decay in nonpolar media. Extension of this analysis to polar solvents shows that this barrier height is a strong function of medium polarity and that the decay pathway becomes near barrierless in more polar media. Thus, the properties of the medium can be used as a route for controlling the motor's excited-state dynamics. The connection between these dynamics and the quantum yield of photochemical isomerization is probed. The photochemical quantum yield is shown to be a much weaker function of solvent polarity, and the most efficient excited-state decay pathway does not lead to a strongly enhanced quantum yield for isomerization. These results are discussed in terms of the solvent dependence of the complex multidimensional excited-state reaction coordinate.</p
Ultrasound-triggered release and activation of drugs and biomacromolecules from nucleic acid scaffolds
In the emerging field of polymer mechanochemistry the advantageous properties ofultrasound (US) can be exploited to control properties on a molecular level byrearranging or cleaving bonds site-specifically. For a successful and selective bondactivation by mechanical stress, a macromolecular framework is required thattransduces the force to the mechanochemically labile bond of the latent molecular motif(the mechanophore). For biomedical applications, the utilization of non-invasive US isparticularly beneficial, as it combines spatial and temporal control with easy regulationof the tissue penetration depth by varying frequency and energy through exposure time.While until now research in mechanochemistry mainly focused on understanding theforce-induced chemical transformations and their impact on material properties,utilization of site-selective bond-scission for drug activation in the field of medicineremained unexplored. In this context, we came up with two feasible ways to activatedrugs and proteins from either poly-nucleic acids or DNA-conjugated nanoparticles bythe treatment of ultrasound, aiming to find applications in the biomedical field. Notably,we presented the first molecular design to activate proteins and drugs from theirdeactivated aptamer-bound parent form by using mechanical force in the form ofultrasound
Genetic Polymorphisms of 5-HT Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia
Background: Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor (HTR) genes HTR1A, HTR2A, HTR3A, and HTR2C and the gene encoding for the serotonin transporter SLC6A4 with MetS in patients with schizophrenia. Methods: A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests. Results: Polymorphic variant rs521018 (HTR2C) was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 (HTR3A) was also associated but did not meet Hardy-Weinberg equilibrium. Conclusions: Our results indicate that allelic variants of HTR2C genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.</p