337 research outputs found
Should ACE2 be given a chance in COVID-19 therapeutics: a semi-systematic review of strategies enhancing ACE2
No full textThe severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 28 million cases of COVID-19 (Corona virus disease-2019) and more than 900000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. Loss of this protective effect could be a major component of COVID-19 pathogenesis. An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1-7) axes, that can be utilized against COVID-19 disease progression
Author response
No full textBlood progenitors within the lymph gland, a larval organ that supports hematopoiesis in Drosophila melanogaster, are maintained by integrating signals emanating from niche-like cells and those from differentiating blood cells. We term the signal from differentiating cells the ‘equilibrium signal’ in order to distinguish it from the ‘niche signal’. Earlier we showed that equilibrium signaling utilizes Pvr (the Drosophila PDGF/VEGF receptor), STAT92E, and adenosine deaminase-related growth factor A (ADGF-A) (Mondal et al., 2011). Little is known about how this signal initiates during hematopoietic development. To identify new genes involved in lymph gland blood progenitor maintenance, particularly those involved in equilibrium signaling, we performed a genetic screen that identified bip1 (bric à brac interacting protein 1) and Nucleoporin 98 (Nup98) as additional regulators of the equilibrium signal. We show that the products of these genes along with the Bip1-interacting protein RpS8 (Ribosomal protein S8) are required for the proper expression of Pvr
Pure Mafia - a novel about child labour, plus thesis and commentary
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This PhD in Creative Writing consists of three parts. The first part is a full-length novel, approximately 80K words, entitled Pure
Mafia. It is a drama about child labour and the Pakistani “carpet mafia”. This is
intertwined with the story of an unhappily married man undergoing a midlife crisis who
has an affair with a younger woman; the latter is instrumental to the main plot about
child labour. The book’s second main theme is British Pakistanis. An overarching theme
is abuse and exploitation, both personal and global, but ultimately of redemption and
renewal. The story is set in 2010/2011, mainly in London, England, with a middle
section in Lahore, Pakistan. The second part is an academic thesis, approximately 20K words, entitled Cheap Labour = Child Labour, on the main theme of the novel, child labour. It attempts to show that child labour is an inevitable consequence of cheap labour generally, and that the only way to tackle child labour is to address cheap labour. The thesis has been consciously and deliberately written as an objective, third person, standalone document and for this reason does not mention the novel. It is partly designed to fulfil the general
PhD criterion of demonstrating scholarship and research. The third part is a subjective, first person critical commentary, approximately 15K words, on the writing of the novel and the thesis, the connection between them, and the research context; it is entitled Pure Mafia: A critical commentary. It explains why
the main thesis is on child labour, rather than on the creative process or an English
Literature thesis; however, the commentary does include in some detail an insight into
the creative process, as well as a discussion of influences and tradition of writing. The final section of the commentary summarises this entire PhD’s original
contribution to knowledge
Optogenetic regulation of protein activity in live cell
No full textSignaling pathways extensively crosstalk among each other and result in different cellular phenotypes depending on the dynamic profile of protein activity. Conventional genetic and pharmacological approaches such as gene overexpression, use of growth factors or inhibitors have helped us delineate interaction maps of signaling components, however these techniques provide limited means to determine contribution of a target protein for specific cellular phenotype. Therefore, to find out the molecular mechanism for a cellular outcome, there is an urgent need for a tool that can specifically activate or inactivate a protein of interest and study it’s role towards a specific cell fate. Optogenetic techniques utilize light to control protein functions with high spatial and temporal resolution. Here, I First present a generalizable light modulated protein stabilization system (GLIMPSe) that enables target-independent optogenetic control of protein activities and minimizes the systematic variation embedded within different photoactivatable proteins. GLIMPSe was applied to control light-mediated post-translational stabilization of two distinct classes of proteins, phosphatase and kinase with rapid kinetics response. Second, I discuss role of speckle-type POZ protein (SPOP) in cell differentiation inhibition in PC12 and primary rat hippocampus neuron cell. Next, I combined the GLIMPSe system with the Sufu protein, a SPOP phenocopy and sonic hedgehog (Shh) signaling pathway inhibitor and generated the GLIMPSe-Sufu system for optogenetic inhibition of Shh signaling pathway. Finally, I review the molecular machinery of cargo trafficking with emphasis on new optogenetic and optochemical experimental strategies that enable direct modulation of cargo trafficking in live cells.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-05-01The student, Payel Mondal, accepted the attached license on 2020-05-01 at 14:55.The student, Payel Mondal, submitted this Dissertation for approval on 2020-05-01 at 15:01.This Dissertation was approved for publication on 2020-05-07 at 14:44.DSpace SAF Submission Ingestion Package generated from Vireo submission #15084 on 2020-08-25 at 17:41:15Made available in DSpace on 2020-08-27T00:50:04Z (GMT). No. of bitstreams: 4
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Reinforcement Learning-Based Design of Side-Channel Countermeasures
No full textDeep learning-based side-channel attacks are capable of breaking targets protected with countermeasures. The constant progress in the last few years makes the attacks more powerful, requiring fewer traces to break a target. Unfortunately, to protect against such attacks, we still rely solely on methods developed to protect against generic attacks. The works considering the protection perspective are few and usually based on the adversarial examples concepts, which are not always easy to translate to real-world hardware implementations. In this work, we ask whether we can develop combinations of countermeasures that protect against side-channel attacks. We consider several widely adopted hiding countermeasures and use the reinforcement learning paradigm to design specific countermeasures that show resilience against deep learning-based side-channel attacks. Our results show that it is possible to significantly enhance the target resilience to a point where deep learning-based attacks cannot obtain secret information. At the same time, we consider the cost of implementing such countermeasures to balance security and implementation costs. The optimal countermeasure combinations can serve as development guidelines for real-world hardware/software-based protection schemes.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit
Subacute Sclerosing Panencephalitis in a 63-Year-Old Woman Presenting as Generalized Choreoathetosis
No full text20.500.12530/87912The persistence of measles virus infection in childhood and early adolescence can rarely lead to a fatal progressive neurodegenerative disorder known as subacute sclerosing panencephalitis (SSPE), characterized by behavioral disturbances and intellectual disability followed by myoclonic jerks and occasional negative myoclonus. Movement disorders are rarely presenting manifestations in SSPE. We herein report a 63-year-old woman with generalized choreoathetosis as the presenting manifestation of stage-I SSPE. Our case was atypical for the patient's age and clinical presentation with generalized choreoathetosis and bilateral putaminal and caudate nucleus signal hyperintensity. Though highly uncommon, neurologists should keep SSPE as a differential diagnosis among patients with movement disorders. Measles-endemic countries should be more vigilant to the atypical and rare presentations of SSPE, such as generalized choreoathetosis
Norovirus-associated neurological manifestations: summarizing the evidence
No full textNorovirus, a positive-stranded RNA virus, is one of the leading causes of acute gastroenteritis among all age groups worldwide. The neurological manifestations of norovirus are underrecognized, but several wide-spectrum neurological manifestations have been reported among infected individuals in the last few years. Our objective was to summarize the features of norovirus-associated neurological disorders based on the available literature. We used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to Jan 30, 2023, using pre‐specified searching strategies. Twenty-one articles were selected for the qualitative synthesis. Among these, seven hundred and seventy-four patients with norovirus-associated neurological manifestations were reported. Most cases were seizure episodes, infection-induced encephalopathy, and immune-driven disorders. However, only a few studies have addressed the pathogenesis of norovirus-related neurological complications. The pathogenesis of these manifestations may be mediated by either neurotropism or aberrant immune-mediated injury, or both, depending on the affected system. Our review could help clinicians to recognize these neurological manifestations better and earlier while deepening the understanding of the pathogenesis of this viral infection.Depto. de MedicinaFac. de MedicinaTRUEpubAPC financiada por la UC
What Do You See? Transforming Fault Injection Target Characterizations
No full textIn fault injection attacks, the first step is to evaluate the target behavior for various fault injection parameters. Showing the results of such a characterization (commonly known as target cartography) is informative and allows researchers to assess the target’s behavior better. Additionally, it helps understand the performance of new search methods or attacks. Thus, publishing obtained results is essential to provide relevant information for reproducibility and benchmarking, improving state-of-the-art results and general security. Unfortunately, publishing the results also allows malicious parties to reverse engineer the information and potentially mount an attack easier. This work discusses how various transformations can be used to occlude sensitive information but, at the same time, still be useful for interested researchers. Our results show that even simple 2D transformations, such as rotation, scaling, and shifting, significantly increase the effort required to reverse engineer the transformed data but maintain the interesting data distribution. Consequently, this work provides a method to allow publishers to share more data in a confidential setting.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit
Language and Cognitive Structures of Emotion [electronic resource] /
No full textThis book examines linguistic expressions of emotion in intensional contexts and offers a formally elegant account of the relationship between language and emotion. The author presents a compelling case for the view that there exist, contrary to popular belief, logical universals at the intersection of language and emotive content. This book shows that emotive structures in the mind that are widely assumed to be not only subjectively or socio-culturally variable but also irrelevant to a general theory of cognition offer an unusually suitable ground for a formal theory of emotive representations, allowing for surprising logical and cognitive consequences for a theory of cognition. Challenging mainstream assumptions in cognitive science and in linguistics, this book will appeal to linguists, philosophers of the mind, linguistic anthropologists, psychologists and cognitive scientists of all persuasions. Prakash Mondal is Assistant Professor of Linguistics and Cognitive Science at the Indian Institute of Technology Hyderabad. He is the author of Language, Mind and Computation (2014), Natural Language and Possible Minds (2016) and Language, Biology and Cognition (completed).Chapter I: Introduction: Intensionality and Emotive Expressions -- Chapter II: How the Intentional Content of Emotion can be Traced to the Intensionality of Emotive Expressions -- Chapter III: Emotive Intensionality, Meaning and Grammar -- Chapter IV: Toward an Architecture of the Language-Emotion Interface -- Chapter V: Conclusion.This book examines linguistic expressions of emotion in intensional contexts and offers a formally elegant account of the relationship between language and emotion. The author presents a compelling case for the view that there exist, contrary to popular belief, logical universals at the intersection of language and emotive content. This book shows that emotive structures in the mind that are widely assumed to be not only subjectively or socio-culturally variable but also irrelevant to a general theory of cognition offer an unusually suitable ground for a formal theory of emotive representations, allowing for surprising logical and cognitive consequences for a theory of cognition. Challenging mainstream assumptions in cognitive science and in linguistics, this book will appeal to linguists, philosophers of the mind, linguistic anthropologists, psychologists and cognitive scientists of all persuasions. Prakash Mondal is Assistant Professor of Linguistics and Cognitive Science at the Indian Institute of Technology Hyderabad. He is the author of Language, Mind and Computation (2014), Natural Language and Possible Minds (2016) and Language, Biology and Cognition (completed)
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