10,557 research outputs found

    Joint Activity Detection, Channel Estimation, and Data Decoding for Grant-free Massive Random Access

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    In the massive machine-type communication (mMTC) scenario, a large number of devices with sporadic traffic need to access the network on limited radio resources. While grant-free random access has emerged as a promising mechanism for massive access, its potential has not been fully unleashed. In particular, the common sparsity pattern in the received pilot and data signal has been ignored in most existing studies, and auxiliary information of channel decoding has not been utilized for user activity detection. This paper endeavors to develop advanced receivers in a holistic manner for joint activity detection, channel estimation, and data decoding. In particular, a turbo receiver based on the bilinear generalized approximate message passing (BiG-AMP) algorithm is developed. In this receiver, all the received symbols will be utilized to jointly estimate the channel state, user activity, and soft data symbols, which effectively exploits the common sparsity pattern. Meanwhile, the extrinsic information from the channel decoder will assist the joint channel estimation and data detection. To reduce the complexity, a low-cost side information-aided receiver is also proposed, where the channel decoder provides side information to update the estimates on whether a user is active or not. Simulation results show that the turbo receiver is able to reduce the activity detection, channel estimation, and data decoding errors effectively, while the side information-aided receiver notably outperforms the conventional method with a relatively low complexity

    The Viability and Potential Consequences of IoT-Based Ransomware

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    With the increased threat of ransomware and the substantial growth of the Internet of Things (IoT) market, there is significant motivation for attackers to carry out IoT-based ransomware campaigns. In this thesis, the viability of such malware is tested. As part of this work, various techniques that could be used by ransomware developers to attack commercial IoT devices were explored. First, methods that attackers could use to communicate with the victim were examined, such that a ransom note was able to be reliably sent to a victim. Next, the viability of using "bricking" as a method of ransom was evaluated, such that devices could be remotely disabled unless the victim makes a payment to the attacker. Research was then performed to ascertain whether it was possible to remotely gain persistence on IoT devices, which would improve the efficacy of existing ransomware methods, and provide opportunities for more advanced ransomware to be created. Finally, after successfully identifying a number of persistence techniques, the viability of privacy-invasion based ransomware was analysed. For each assessed technique, proofs of concept were developed. A range of devices -- with various intended purposes, such as routers, cameras and phones -- were used to test the viability of these proofs of concept. To test communication hijacking, devices' "channels of communication" -- such as web services and embedded screens -- were identified, then hijacked to display custom ransom notes. During the analysis of bricking-based ransomware, a working proof of concept was created, which was then able to remotely brick five IoT devices. After analysing the storage design of an assortment of IoT devices, six different persistence techniques were identified, which were then successfully tested on four devices, such that malicious filesystem modifications would be retained after the device was rebooted. When researching privacy-invasion based ransomware, several methods were created to extract information from data sources that can be commonly found on IoT devices, such as nearby WiFi signals, images from cameras, or audio from microphones. These were successfully implemented in a test environment such that ransomable data could be extracted, processed, and stored for later use to blackmail the victim. Overall, IoT-based ransomware has not only been shown to be viable but also highly damaging to both IoT devices and their users. While the use of IoT-ransomware is still very uncommon "in the wild", the techniques demonstrated within this work highlight an urgent need to improve the security of IoT devices to avoid the risk of IoT-based ransomware causing havoc in our society. Finally, during the development of these proofs of concept, a number of potential countermeasures were identified, which can be used to limit the effectiveness of the attacking techniques discovered in this PhD research

    Corporate Social Responsibility: the institutionalization of ESG

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    Understanding the impact of Corporate Social Responsibility (CSR) on firm performance as it relates to industries reliant on technological innovation is a complex and perpetually evolving challenge. To thoroughly investigate this topic, this dissertation will adopt an economics-based structure to address three primary hypotheses. This structure allows for each hypothesis to essentially be a standalone empirical paper, unified by an overall analysis of the nature of impact that ESG has on firm performance. The first hypothesis explores the evolution of CSR to the modern quantified iteration of ESG has led to the institutionalization and standardization of the CSR concept. The second hypothesis fills gaps in existing literature testing the relationship between firm performance and ESG by finding that the relationship is significantly positive in long-term, strategic metrics (ROA and ROIC) and that there is no correlation in short-term metrics (ROE and ROS). Finally, the third hypothesis states that if a firm has a long-term strategic ESG plan, as proxied by the publication of CSR reports, then it is more resilience to damage from controversies. This is supported by the finding that pro-ESG firms consistently fared better than their counterparts in both financial and ESG performance, even in the event of a controversy. However, firms with consistent reporting are also held to a higher standard than their nonreporting peers, suggesting a higher risk and higher reward dynamic. These findings support the theory of good management, in that long-term strategic planning is both immediately economically beneficial and serves as a means of risk management and social impact mitigation. Overall, this contributes to the literature by fillings gaps in the nature of impact that ESG has on firm performance, particularly from a management perspective

    Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms

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    Das ösophageale Adenokarzinom zeigt eine global steigende Inzidenz und hat mit einer 5-Jahres-Überlebensrate von weniger als 25% eine schlechte Prognose. Personalisierte Therapieansätze sind selten und prognostische/prädiktive Biomarker des Tumormikromilieus sind unzureichend charakterisiert. Die kumulative Promotion nähert sich dieser Problematik in drei unterschiedlichen Schwerpunkten. 1. Zur Identifizierung Kompartiment-spezifischer Biomarker wurde eine Methode entwickelt, welche als kostengünstige Alternative zum sc-Seq Expressionsprofile individueller Zelltypen generiert. Dabei erfolgt die Extraktion der RNA nicht aus Einzelzellen, sondern aus flowzytometrisch-getrennten Zellkompartimenten. Die Separation der Proben in Epithelzellen, Immunzellen und Fibroblasten wurde durch verschiedene Verfahren validiert und eine suffiziente Ausbeute an RNA auch für kleine Gewebemengen gezeigt. 2. Biomarker des Immunzellkompartiments als therapeutische Angriffspunkte wurden in einem Patientenkollektiv von bis zu 551 Patienten auf ihre Bedeutung beim EAC überprüft. Es zeigte sich eine Expression der Immuncheckpoints LAG3, VISTA und IDO auf TILs durch IHC und RNA-Sonden basierte Verfahren in einem relevanten Anteil (LAG3: 11,4%, VISTA: 29%, IDO: 52,6%). Es konnte eine prognostisch günstige Bedeutung der VISTA, LAG3 und IDO Expression gezeigt werden. Durch den Vergleich von Genexpressionsprofilen aus therapienaiven und vorbehandelten Tumoren konnte zudem ein immunsuppressiver Effekt von neoadjuvanten Therapiekonzepten auf das Tumormikromilieu des EACs gezeigt werden. Dabei kam es zur verminderten Expression von Checkpoints und Anzahl TILs nach (Radio-) Chemotherapie. 3. Im Tumorzellkompartiment wurde die Rolle von Amplifikationen in ErbB-Rezeptor abhängigen Signalwegen durch FISH-Technik und Immunhistochemie evaluiert. Es fanden sich KRAS Amplifikationen in 17,1%, PIK3CA Amplifikationen in 5% sowie eine HER2/neu-Überexpression in 14,9% der untersuchten Tumore

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    A Molecular Approach to the Diagnosis, Assessment, Monitoring and Treatment of Pulmonary Non-Tuberculous Mycobacterial Disease

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    Introduction: Non-Tuberculous Mycobacteria (NTM) can cause disease of the lungs and sinuses, lymph nodes, joints and central nervous system as well as disseminated infections in immunocompromised individuals. Efforts to tackle infections in NTM are hampered by a lack of reliable biomarkers for diagnosis, assessment of disease activity, and prognostication. Aims: The broad aims of this thesis are: 1. to develop molecular assays capable of quantifying the 6 most common pathogenic mycobacteria (M. abscessus, M. avium, M. intracellulare, M. malmoense, M. kansasii, M. xenopi) and calculate comparative sensitivities and specificities for each assay. 2. to assess patients’ clinical course over 12 – 18 months by performing the developed molecular assays against DNA extracted from sputum from patients with NTM infection. 3. to assess dynamic bacterial changes of the lung microbiome in patients on treatment for NTM disease and those who are treatment na ve. Methods: DNA was extracted from a total of 410 sputum samples obtained from 38 patients who were either: • commencing treatment for either M. abscessus or Mycobacterium avium complex. • considered colonised with M. abscessus or Mycobacterium avium complex (i.e. cultured NTM but were not deemed to have infection as they did not meet ATS or BTS criteria for disease). • Diagnosed with cystic fibrosis (CF) or non-CF bronchiectasis but had never cultured NTM. For the development of quantitative molecular assays, NTM hsp65 gene sequences were aligned and interrogated for areas of variability. These variable regions enabled the creation of species specific probes. In vitro sensitivity and specificity for each probe was determined by testing each probe against a panel of plasmids containing hsp65 gene inserts from different NTM species. Quantification accuracy was determined by using each assay against a mock community containing serial dilutions of target DNA. Each sample was tested with the probes targeting: M. abscessus, M. avium and M. intracellulare producing a longitudinal assessment of NTM copy number during each patient’s clinical course. In addition, a total of 64 samples from 16 patients underwent 16S rRNA gene sequencing to characterise longitudinal changes in the microbiome of both NTM disease and controls. Results: In vitro sensitivity for the custom assays were 100% and specificity ranged from 91.6% to 100%. In terms of quantification accuracy, there was no significant difference between the measured results of each assay and the expected values when performed in singleplex. The assays were able to accurately determine NTM copy number to a theoretical limit of 10 copies/μl. When used against samples derived from human sputum and using culture results as a gold standard, the sensitivity of the assay for M. abscessus was found to be 0.87 and 0.86 for MAC. The specificity of the assay for M. abscessus was 0.95 and 0.62 for MAC. The negative predictive value of the assay for M. abscessus was 0.98 and 0.95 for MAC. This resulted in an AUC of 0.92 for M. abscessus and 0.74 for MAC. Longitudinal analysis of the lung microbiome using 16SrRNA gene sequencing showed that bacterial burden initially decreases after initiation of antibiotic therapy but begins to return to normal levels over several months of antibiotic therapy. This effect is mirrored by changes in alpha diversity. The decrease in bacterial burden and loss of alpha diversity was found to be secondary to significant changes in specific genera such as Veillonella and Streptococcus. The abundance of other Proteobacteria such as Pseudomonas remain relatively constant. Conclusion: The molecular assay has shown high in vitro sensitivity and specificity for the detection and accurate quantification of the 6 most commonly pathogenic NTM species. The assays successfully identified NTM DNA from human sputum samples. A notable association between NTM copy number and the cessation of one or more antibiotics existed (i.e. when one antibiotic was stopped because of patient intolerance, NTM copy number increased, often having been unrecordable prior to this). The qPCR assays developed in this thesis provide an affordable, real time and rapid measurement of NTM burden allowing clinicians to act on problematic results sooner than currently possible. There was no significant difference between the microbiome in bronchiectasis and cystic fibrosis nor was there a significant difference between the microbiome in patients requiring treatment for NTM and those who did not. Patients receiving treatment experienced an initial decrease in bacterial burden over the first weeks of treatment followed by a gradual increase towards baseline over the next weeks to months. This change was mirrored in measures of alpha diversity. Changes in abundance and diversity were accounted for by decreases in specific bacteria whilst the abundance of other bacteria increased, occupying the microbial niche created. These bacteria (for example Pseudomonas spp) are often associated with morbidity.Open Acces

    A suite of quantum algorithms for the shortestvector problem

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    Crytography has come to be an essential part of the cybersecurity infrastructure that provides a safe environment for communications in an increasingly connected world. The advent of quantum computing poses a threat to the foundations of the current widely-used cryptographic model, due to the breaking of most of the cryptographic algorithms used to provide confidentiality, authenticity, and more. Consequently a new set of cryptographic protocols have been designed to be secure against quantum computers, and are collectively known as post-quantum cryptography (PQC). A forerunner among PQC is lattice-based cryptography, whose security relies upon the hardness of a number of closely related mathematical problems, one of which is known as the shortest vector problem (SVP). In this thesis I describe a suite of quantum algorithms that utilize the energy minimization principle to attack the shortest vector problem. The algorithms outlined span the gate-model and continuous time quantum computing, and explore methods of parameter optimization via variational methods, which are thought to be effective on near-term quantum computers. The performance of the algorithms are analyzed numerically, analytically, and on quantum hardware where possible. I explain how the results obtained in the pursuit of solving SVP apply more broadly to quantum algorithms seeking to solve general real-world problems; minimize the effect of noise on imperfect hardware; and improve efficiency of parameter optimization.Open Acces

    The Impact of a Play Intervention on the Social-Emotional Development of Preschool Children in Riyadh, Saudi Arabia

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    Practitioners working with children have emphasized that play is vital to children’s development, Links between children’s social-emotional development and play have been widely documented. However, rigorous research evidence of these links remains limited. This study’s objectives were to measure the impact of play on children’s social-emotional development in the kingdom of Saudi Arabia; identify teachers’ viewpoints around the use of play intervention; and understand the children’s experience of play intervention. Fifty-nine children aged between five and six years, with mean age of 5.5 (SD 3.376) and eight teachers participated in the study. The study used a mixed-method strategy including questionnaires, interviews, and focus group discussions. Children’s social-emotional development was measured by using the Strengths and Difficulties Questioner (SDQ). A pre-/post-test counterbalanced design was used to measure the impact of the play intervention on children’s development. Teachers’ perspectives on play were obtained by interviewing eight teachers. Children’s views were gathered through focus group discussions. Repeated measures ANOVA was conducted to determine the differences in the SDQ score over three time points. Results showed that using unstructured loose parts play had positively impacted children’s social-emotional development. After participation in the play intervention, scores from the SDQ indicated that children demonstrated significantly less problematic emotional, conduct and peer relationship issues. They also scored significantly higher in their positive prosocial behaviour. These positive effects were sustained after six weeks of stopping the intervention. The play intervention did not however impact children’s hyperactivity level. The interviews analysis illustrates four main themes: concept and characteristics of play, play functions, developmental benefits of play, and play and practice. Regarding children’s discussion, affordance emerged as a main theme; this includes emotional, social, and functional affordances. Unstructured loose parts play intervention was demonstrated to have positive impacts on children’s social-emotional development. The study’s findings support the view that play is a way to increase children’s development

    Freelance subtitlers in a subtitle production network in the OTT industry in Thailand: a longitudinal study

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    The present study sets out to investigate a subtitle production network in the over-the-top (OTT) industry in Thailand through the perspective of freelance subtitlers. A qualitative longitudinal research design was adopted to gain insights into (1) the way the work practices of freelance subtitlers are influenced by both human and non-human actors in the network, (2) the evolution of the network, and (3) how the freelance subtitlers’ perception of quality is influenced by changes occurring in the network. Eleven subtitlers were interviewed every six months over a period of two years, contributing to over 60 hours of interview data. The data analysis was informed by selected concepts from Actor-Network Theory (ANT) (Law 1992, 2009; Latour 1996, 2005; Mol 2010), and complemented by the three-dimensional quality model proposed by Abdallah (2016, 2017). Reflexive thematic analysis (Braun and Clarke 2019a, 2020b) was used to generate themes and sub-themes which address the research questions and tell compelling stories about the actor-network. It was found that from July 2017 to September 2019, the subtitle production network, which was sustained by complex interrelationships between actors, underwent a number of changes. The changes affected the work practices of freelance subtitlers in a more negative than positive way, demonstrating their precarious position in an industry that has widely adopted the vendor model (Moorkens 2017). Moreover, as perceived by the research participants, under increasingly undesirable working conditions, it became more challenging to maintain a quality process and to produce quality subtitles. Finally, translation technology and tools, including machine translation, were found to be key non-human actors that catalyse the changes in the network under study
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