10,940 research outputs found
Bildung in der digitalen Transformation
Die Coronapandemie und der durch sie erzwungene zeitweise Ăbergang von PrĂ€senz- zu Distanzlehre haben die Digitalisierung des Bildungswesens enorm vorangetrieben. Noch deutlicher als vorher traten dabei positive wie negative Aspekte dieser Entwicklung zum Vorschein. WĂ€hrend den Hochschulen der Wechsel mit vergleichsweise geringen Reibungsverlusten gelang, offenbarten sich diese an Schulen weitaus deutlicher. Trotz aller Widrigkeiten erscheint eines klar: Die zeitweisen VerĂ€nderungen werden Nachwirkungen zeigen. Eine völlige RĂŒckkehr zum Status quo ante ist kaum noch vorstellbar. Zwei Fragen bestimmen vor diesem Hintergrund die Doppelgesichtigkeit des Themas der 29. Jahrestagung der Gesellschaft fĂŒr Medien in der Wissenschaft (GMW). Erstens: Wie âfunktioniertâ Bildung in der sich derzeit ereignenden digitalen Transformation und welche Herausforderungen gibt es? Und zweitens: Befindet sich möglicherweise Bildung selbst in der Transformation? BeitrĂ€ge zu diesen und weiteren Fragen vereint der vorliegende Tagungsband
Endogenous measures for contextualising large-scale social phenomena: a corpus-based method for mediated public discourse
This work presents an interdisciplinary methodology for developing endogenous measures of group membership through analysis of pervasive linguistic patterns in public discourse. Focusing on political discourse, this work critiques the conventional approach to the study of political participation, which is premised on decontextualised, exogenous measures to characterise groups. Considering the theoretical and empirical weaknesses of decontextualised approaches to large-scale social phenomena, this work suggests that contextualisation using endogenous measures might provide a complementary perspective to mitigate such weaknesses.
This work develops a sociomaterial perspective on political participation in mediated discourse as affiliatory action performed through language. While the affiliatory function of language is often performed consciously (such as statements of identity), this work is concerned with unconscious features (such as patterns in lexis and grammar). This work argues that pervasive patterns in such features that emerge through socialisation are resistant to change and manipulation, and thus might serve as endogenous measures of sociopolitical contexts, and thus of groups.
In terms of method, the work takes a corpus-based approach to the analysis of data from the Twitter messaging service whereby patterns in usersâ speech are examined statistically in order to trace potential community membership. The method is applied in the US state of Michigan during the second half of 2018â6 November having been the date of midterm (i.e. non-Presidential) elections in the United States. The corpus is assembled from the original posts of 5,889 users, who are nominally geolocalised to 417 municipalities. These users are clustered according to pervasive language features. Comparing the linguistic clusters according to the municipalities they represent finds that there are regular sociodemographic differentials across clusters. This is understood as an indication of social structure, suggesting that endogenous measures derived from pervasive patterns in language may indeed offer a complementary, contextualised perspective on large-scale social phenomena
Security and Privacy Problems in Voice Assistant Applications: A Survey
Voice assistant applications have become omniscient nowadays. Two models that
provide the two most important functions for real-life applications (i.e.,
Google Home, Amazon Alexa, Siri, etc.) are Automatic Speech Recognition (ASR)
models and Speaker Identification (SI) models. According to recent studies,
security and privacy threats have also emerged with the rapid development of
the Internet of Things (IoT). The security issues researched include attack
techniques toward machine learning models and other hardware components widely
used in voice assistant applications. The privacy issues include technical-wise
information stealing and policy-wise privacy breaches. The voice assistant
application takes a steadily growing market share every year, but their privacy
and security issues never stopped causing huge economic losses and endangering
users' personal sensitive information. Thus, it is important to have a
comprehensive survey to outline the categorization of the current research
regarding the security and privacy problems of voice assistant applications.
This paper concludes and assesses five kinds of security attacks and three
types of privacy threats in the papers published in the top-tier conferences of
cyber security and voice domain.Comment: 5 figure
Ecological successions throughout the desiccation of Tirez lagoon (Spain) as an astrobiological time-analog for wet-to-dry transitions on Mars
Tirez was a small and seasonal endorheic athalassohaline lagoon that was located in central Spain. In recent years, the lagoon has totally dried out, offering for the first time the opportunity to analyze its desiccation process as a âtime-analogâ to similar events occurred in paleolakes with varying salinity during the wet-to-dry transition on early Mars. On the martian cratered highlands, an early period of water ponding within enclosed basins evolved to a complete desiccation of the lakes, leading to deposition of evaporitic sequences during the Noachian and into the Late Hesperian. As Tirez also underwent a process of desiccation, here we describe (i) the microbial ecology of Tirez when the lagoon was still active 20 years ago, with prokaryotes adapted to extreme saline conditions; (ii) the composition of the microbial community in the dried lake sediments today, in many case groups that thrive in sediments of extreme environments; and (iii) the molecular and isotopic analysis of the lipid biomarkers that can be recovered from the sediments today. We discuss the implications of these results to better understanding the ecology of possible Martian microbial communities during the wet-to-dry transition at the end of the Hesperian, and how they may inform about research strategies to search for possible biomarkers in Mars after all the water was los
Targeting Fusion Proteins of HIV-1 and SARS-CoV-2
Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.</p
Survey on Thai NLP Language Resources and Tools
Over the past decades, Natural Language Processing (NLP) research has been expanding to cover more languages. Recently particularly, NLP community has paid increasing attention to under-resourced languages. However, there are still many languages for which NLP research is limited in terms of both language resources and software tools. Thai language is one of the under-resourced languages in the NLP domain, although it is spoken by nearly 70 million people globally. In this paper, we report on our survey on the past development of Thai NLP research to help understand its current state and future research directions. Our survey shows that, although Thai NLP community has achieved a significant achievement over the past three decades, particularly on NLP upstream tasks such as tokenisation, research on downstream tasks such as syntactic parsing and semantic analysis is still limited. But we foresee that Thai NLP research will advance rapidly as richer Thai language resources and more robust NLP techniques become available
Investigating the chromatin dynamics of gene activation
Enhancers are cis-regulatory elements which contribute to the activation of
gene expression. The spatio-temporal control of gene expression is
particularly important during embryonic development, when the expression of
developmental regulators is tightly controlled. Sonic hedgehog (Shh) is an
important signalling protein which is vital for the patterning of the embryo.
Shh is expressed throughout the developing central nervous system, gut and
the posterior limb bud. This complex pattern of expression is regulated by the
activity of multiple tissue-specific enhancers which are spread through a 1
Mb genomic desert. Many of these enhancers activate Shh expression over
large genomic distances, with some enhancers being located within the
intron of neighbouring genes.
The textbook model for enhancer-mediated gene activation suggests that an
enhancer moves within close proximity to its target promoter, recruiting
transcription factors and RNA polymerase II to the gene and promoting
transcription. However, recent studies have brought this model into question.
Understanding the dynamics of enhancers and promoters during
transcriptional activation is vital for comprehending how gene expression is
regulated by enhancers. Advances in techniques enabling the labelling and
tracking of non-repetitive loci in live cells have allowed this to start to be
addressed.
To study how Shh expression is regulated by its enhancers in live cells, firstly
I needed to develop a system where Shh expression could be activated in
cultured cells. It was known that Shh expression could be activated in mouse
embryonic stem cells (mESCs) through retinoic acid treatment; however, the
enhancer responsible for activating Shh expression and the cell type the
mESCs differentiate into were previously unknown. I investigated changes in
chromatin accessibility and modifications to show that Shh expression is
activated from endodermal enhancers when mESCs are differentiated with
retinoic acid. RNA-seq confirmed that the resulting cells express several
markers of early endoderm and mesoderm lineages.
The identification of enhancers which activate Shh expression in this mESC
differentiation system allowed the tagging and tracking of these loci using a
CRISPR-based live cell DNA imaging system. I developed a system that is
versatile, simple and stable, with a view to decrease the number of guide
RNAs required in order to visualise non-repetitive loci. The dynamics of the
Shh promoter and were determined in cells where Shh was transcriptionally
silent or active. I found that the dynamics of these cis-regulatory elements
were sub-diffusive despite gene activity. Overall, through quantitative
CRISPR-imaging, I found direct measurements for chromatin mobility of cis-regulatory elements in living cells under different states of activity
RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinsonâs disease targeting RNA/HuR complexes
MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy.
HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinsonâs disease (PD).
PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies.
In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD.
To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells.
To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3â untranslated region (3â-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression.
In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies
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After Creation: Intergovernmental Organizations and Member State Governments as Co-Participants in an Authority Relationship
This is a re-amalgamation of what started as one manuscript and became two when the length proved to be more than any publisher wanted to consider. The splitting consisted of removing what are now Parts 3, 4, and 5 so that the manuscript focused on the outcome-related shared beliefs holding an authority relationship together. Those parts were last worked on in 2018. The rest were last worked on in late 2021 but also remain incomplete.
The relational approach adopted in this study treats intergovernmental organizations and the governments of member states as co-participants in an authority relationship with the governments of their member states. Authority relationships link two types of actor, defined by their authority-holder or addressee role in the relationship, through a set of shared beliefs about why the relationship exists and how the participants should fulfill their respective roles. The IGO as authority holder has a role that includes a right to instruct other actors about what they should or should not do; the governments of member states as addressees are expected to comply with the instructions. Three sets of shared beliefs provide the conceptual âglueâ holding the relationship together. The first defines the goal of the collective effort, providing both the rationale for having the authority relationship and providing a lode star for assessments of the collective effortâs success or lack of success. The second set defines the shared understanding about allocation of roles and the process of interaction by establishing shared expectations about a) the selection process by which particular actors acquire authority holder roles, b) the definitions identifying one or more categories of addressees expected to follow instructions, and c) the procedures through which the authority holder issues instructions. The third set focus on the outcomes of cooperation through the relationship by defining a) the substantive areas in which the authority holder may issue instructions, b) the bases for assessing the relevance actions mandated in instructions for reaching the goal, and c) the relative efficacy of action paths chosen for reaching the goal as compared to other possible action paths.
Using an authority relationship framework for analyzing cooperation through IGOs highlights the inherently bi-directional nature of IGO-member government activity by viewing their interaction as involving a three-step process in which the IGO as authority holder decides when to issue what instruction, the member state governments as followers react to the instruction with anything from prompt and full compliance through various forms of pushback to outright rejection, and the IGO as authority holder responds to how the followers react with efforts to increase individual compliance with instructions and reinforce continuing acceptance of the authority relationship. Foregrounding the dynamics produced by the interaction of these two streams of perception and action reveals more clearly how far intergovernmental organizations acquire capacity to operate as independent actors, the dynamic ways they maintain that capacity, and how much they influence member governmentsâ beliefs and actions at different times. The approach fosters better understanding of why, when, and for how long governments choose cooperation through an IGO even in periods of rising unilateralism
Contribution of non-canonical DNA G-quadruplex structures to premature ageing
Previous studies have identified Cockayne Syndrome B (CSB) as a helicase that can resolve non-canonical DNA structures, called G-quadruplexes (G4s). The aim of this study is to investigate the properties of CSB as a G4-binder and -resolvase, and examine the correlation between the G4-helicase activity of CSB and premature ageing phenotype observed in CSB-deficient cells. Accordingly, the recombinant CSB full-length protein (FL) and its helicase- âlike" domain (HD) were respectively expressed from insect and bacterial cells, and their resolvase and binding activities were tested over a large panel of DNA substrates. Native gel analysis and biophysical characterisations revealed that ribosomal DNA (rDNA) sequences, that typically act as CSB substrate, can form intermolecular G4s. We discovered that intermolecular G4s were strongly bound by CSB with picomolar affinity, whilst negligible binding to intramolecular G4s was observed. In vitro and cellular data demonstrated that G4-ligands can compete with CSB for binding to intermolecular rDNA G4, which results in CSB being displaced off the nucleoli of cells upon treatment with G4-ligands. Immunostaining with the selective G4-antibody BG4 revealed a lack of BG4-staining in the nucleoli of CSB-deficient cells after exogenous expression of recombinant CSB, further corroborating the hypothesis that CSB can bind intermolecular rDNA G4s in the nucleoli and compete with BG4 for the binding of such DNA-substrate. The work presented in this thesis allowed us to observe that (I) intermolecular G4s are likely to form from long-range distant rDNA sequences within the nucleoli of cells, and (II) CSB specifically binds and resolves these structures. Our results provide the first evidence of an endogenous protein that specifically interacts with intermolecular G4s, suggesting potential biological significance of these structures. The biological relevance of intermolecular rDNA G4s could be key in rare genetic disorders like Cockayne Syndrome, where senescence and premature ageing is observed when CSB is functionally mutated.Open Acces
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