19,254 research outputs found

    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

    Quantum resonances and analysis of the survival amplitude in the nonlinear Winter's model

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    In this paper we show that the typical effects of quantum resonances, namely, the exponential-type decay of the survival amplitude, continue to exist even when a nonlinear perturbative term is added to the time-dependent Schroedinger equation. The difficulty in giving a rigorous and appropriate definition of quantum resonances by means of the notions already used for linear equations is also highlighted.Comment: 31 pages, 8 figure

    Animating potential for intensities and becoming in writing: challenging discursively constructed structures and writing conventions in academia through the use of storying and other post qualitative inquiries

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    Written for everyone ever denied the opportunity of fulfilling their academic potential, this is ‘Chloe’s story’. Using composite selves, a phrase chosen to indicate multiplicities and movement, to story both the initial event leading to ‘Chloe’s’ immediate withdrawal from a Further Education college and an imaginary second chance to support her whilst at university, this Deleuzo-Guattarian (2015a) ‘assemblage’ of post qualitative inquiries offers challenge to discursively constructed structures and writing conventions in academia. Adopting a posthuman approach to theorising to shift attention towards affects and intensities always relationally in action in multiple ‘assemblages’, these inquiries aim to decentre individual ‘lecturer’ and ‘student’ identities. Illuminating movements and moments quivering with potential for change, then, hoping thereby to generate second chances for all, different approaches to writing are exemplified which trouble those academic constraints by fostering inquiry and speculation: moving away from ‘what is’ towards ‘what if’. With the formatting of this thesis itself also always troubling the rigid Deleuzo-Guattarian (2015a) ‘segmentary lines’ structuring orthodox academic practice, imbricated in these inquiries are attempts to exemplify Manning’s (2015; 2016) ‘artfulness’ through shifts in thinking within and around an emerging PhD thesis. As writing resists organising, the verb thesisising comes into play to describe the processes involved in creating this always-moving thesis. Using ‘landing sites’ (Arakawa and Gins, 2009) as a landscaping device, freely creating emerging ‘lines of flight’ (Deleuze and Guattari, 2015a) so often denied to students forced to adhere to strict academic conventions, this ‘movement-moving’ (Manning, 2014) opens up opportunities for change as in Manning’s (2016) ‘research-creation’. Arguing for a moving away from writing-representing towards writing-inquiring, towards a writing ‘that does’ (Wyatt and Gale, 2018: 127), and toward writing as immanent doing, it is hoped to animate potential for intensities and becoming in writing, offering opportunities and glimmerings of the not-yet-known

    In vitro investigation of the effect of disulfiram on hypoxia induced NFÎșB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines

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    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM. This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFÎșB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFÎșB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFÎșB in maintaining GSC phenotypes. The study also highlighted the significance of NFÎșB in driving chemoresistance, invasiveness, and the potential role of NFÎșB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration. In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFÎșB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations. DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients

    Unresolved taxonomy confounds invasive species identification: the Lysmata vittata Stimpson, 1860 (Decapoda: Caridea: Lysmatidae) species complex and recent introduction of Lysmata vittata sensu stricto in the western Atlantic

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    Peppermint shrimp resembling Lysmata vittata Stimpson, 1860, a species native to the Indo- West Pacific, were found in the lower Chesapeake Bay and adjacent coastal embayments in 2013, representing the first recorded introduction of this species in the northwestern Atlantic. Conflicting morphological descriptions, inconsistent morphological terminology, and limited molecular data (i.e., unresolved taxonomy), as well as the destruction of the type material of L. vittata, created uncertainty regarding proper identification. We provide the first phylogeny incorporating individuals from across the presumed native and introduced range of L. vittata. Morphological and phylogenetic analyses clearly indicate L. vittata represents a species complex of two widely divergent groups: 1) “Bruce Type” with a uniramous dorsal antennule that agrees with A.J. Bruce’s 1990 redescription of L. vittata, and 2) “Rauli Type” with a one-article accessory branch on the dorsal antennule that agrees most closely with the junior synonym L. rauli Laubenheimer & Rhyne, 2010. Given the taxonomic ambiguity surrounding L. vittata, we designate the individual used by A.J. Bruce to redescribe L. vittata and incorporated in our analyses as a neotype to fix the identity of this species. We therefore identify introduced North American and New Zealand populations as L. vittata sensu stricto and postulate that the native range spans temperate/subtropical East Asia. These data suggest that L. rauli is a valid species, which includes a possible undescribed sister species. We confirm the presence of L. californica Stimpson, 1866 in New Zealand, the first non-native record for this species. We also provide data suggesting L. dispar Hayashi, 2007 may be more widespread in the Indo-West Pacific than currently known and consider L. lipkei Okuno & Fiedler, 2010 to be a likely junior synonym

    Proof of Concept of Therapeutic Gene Modulation of MBNL1/2 in Myotonic Dystrophy

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    La distrofia miotĂłnica tipo 1 es una enfermedad genĂ©tica rara multisistĂ©mica que afecta a 1 de cada 3000-8000 personas. La causa molecular de la enfermedad proviene de repeticiones tĂłxicas “CTG” en el gen DMPK (DM Protein Kinase). Tras la transcripciĂłn, estas repeticiones forman una estructura de horquilla que se une con alta afinidad a la familia de proteĂ­nas MBNL (Muscleblind-like) que agota su funciĂłn de regulaciĂłn de la poliadenilaciĂłn y el splicing alternativo postranscripcional en numerosos transcritos. La pĂ©rdida de funciĂłn de MBNL provoca una cascada de efectos posteriores, que eventualmente conducen a sĂ­ntomas clĂ­nicos que incluyen miotonĂ­a, debilidad y atrofia muscular, cataratas, disfunciĂłn cardĂ­aca y trastorno cognitivo. La restauraciĂłn de la funciĂłn de la proteĂ­na MBNL es clave para aliviar los sĂ­ntomas debilitantes de esta enfermedad. Se han utilizado oligonucleĂłtidos antisentido (AON) para apuntar a las repeticiones de DMPK y liberar MBNL del secuestro, lo que da como resultado resultados terapĂ©uticos prometedores en modelos celulares y animales de la enfermedad. Otro factor que interviene en la pĂ©rdida de funciĂłn de las proteĂ­nas MBNL son los miRNAs que regulan su traducciĂłn. AquĂ­ se muestra el uso de AON dirigidos a la actividad de miR-23b y miR-218, que se ha demostrado previamente que regulan directamente MBNL1 y MBNL2. Estos antimiRs recibieron modificaciones FANA para aumentar su entrega en las cĂ©lulas y reducir la toxicidad. TambiĂ©n se probaron los AON, denominados blockmiRs, que se unen de manera complementaria a los sitios de uniĂłn confirmados de miR-23b y miR-218 en los 3'-UTR de las transcripciones de MBNL1 y MBNL2. De esta manera, los miRNAs no pueden unirse y regular la traducciĂłn de MBNL, lo que aumenta la cantidad de proteĂ­na MBNL producida en una cĂ©lula deficiente. AquĂ­ se propone el uso de AON de nuevo diseño dirigidos a la actividad de miR-23b y miR-218 para regular MBNL1 y MBNL2 a travĂ©s de (1) exploraciĂłn del bloqueo de miRNA a travĂ©s de FANA-antimiR AON in vitro, (2) exploraciĂłn del bloqueo del sitio de uniĂłn de miRNA a travĂ©s de la estrategia blockmiR in vitro e in vivo con el uso de modificaciones quĂ­micas de LNA, y (3) mejora de la quĂ­mica de la estrategia blockmiR mediante el uso de tecnologĂ­a de pĂ©ptidos de penetraciĂłn celular in vitro e in vivo.Myotonic Dystrophy Type 1 is a multi-systemic rare genetic disease affecting 1 in 3000-8000 people. The molecular cause of the disease stems from toxic “CTG” repetitions in the DMPK (DM Protein Kinase) gene. Upon transcription, these repetitions form a hairpin structure that binds with high affinity to the MBNL (Muscleblind-like) family of proteins depleting their function of post-transcriptional alternative splicing and polyadenylation regulation on numerous transcripts. MBNL loss-of-function causes a cascade of downstream effects, which eventually lead to clinical symptoms including myotonia, muscle weakness and atrophy, cataracts, cardiac dysfunction, and cognitive disorder. The restoration of MBNL protein function is key to relieving the debilitating symptoms of this disease. Antisense oligonucleotides (AONs) have been used to target the DMPK repeats and release MBNL from sequestration resulting in promising therapeutic results in cellular and animal models of the disease. Another factor playing a role in the loss-of-function of MBNL proteins are the miRNAs that regulate their translation. Here is shown the use of AONs targeting miR-23b and miR-218 activity, which have been previously shown to directly regulate MBNL1 and MBNL2. These antimiRs were given FANA modifications to increase their delivery in cells and lower toxicity. Also tested are AONs, termed blockmiRs, that complementary bind to the confirmed binding sites of miR-23b and miR-218 in the 3’-UTRs of MBNL1 and MBNL2 transcripts. In this way, the miRNAs are unable to bind and regulate the translation of MBNL thereby augmenting the amount of MBNL protein made in an otherwise deficient cell. Proposed here is the use of newly designed AONs targeting miR-23b and miR-218 activity in order to regulate MBNL1 and MBNL2 through (1) exploration of miRNA blocking through FANA-antimiR AONs in vitro, (2) exploration of miRNA binding site blocking through blockmiR strategy in vitro and in vivo with the use of LNA chemical modifications, and (3) improvement of the chemistry of the blockmiR strategy through the use of cell penetrating peptide technology in vitro and in vivo

    Programmes d'intervention familiale intensive : ajustement des interventions et évolution des familles présentant des profils cliniques distincts

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    La prĂ©sente thĂšse par articles porte sur les programmes d’intervention familiale intensive et s’inscrit dans le cadre du programme de doctorat en psychoĂ©ducation de l’UniversitĂ© de Sherbrooke ayant pour thĂšme Les difficultĂ©s de comportement des enfants et des adolescents et les interventions psychoĂ©ducatives. Les donnĂ©es utilisĂ©es pour rĂ©aliser cette thĂšse proviennent de l’étude de PauzĂ© et ses collĂšgues (2014) visant Ă  examiner l’impact de l’application fidĂšle du programme Crise-Ado-Famille-Enfance (CAFE). Les programmes d’intervention familiale intensive, Ă©laborĂ©s afin de prĂ©venir le placement d’urgence des jeunes en milieu substitut et s’adressant particuliĂšrement aux adolescent(e)s prĂ©sentant des problĂšmes de comportement et Ă  leur famille, sont largement implantĂ©s au QuĂ©bec et en AmĂ©rique du Nord. Ces programmes offrent une intervention ajustĂ©e aux profils cliniques des familles et ciblent Ă  la fois l’urgence de la situation de crise et les facteurs psychosociaux en cause dans l’émergence et le maintien de la crise familiale et des problĂšmes de comportement des adolescent(e)s. Plusieurs mĂ©ta-analyses ont dĂ©montrĂ© l’efficacitĂ© de ces programmes, notamment pour rĂ©duire les taux de placement en milieu substitut, diminuer les problĂšmes de comportement des adolescent(e)s et amĂ©liorer le fonctionnement familial. Toutefois, les rĂ©sultats de ces mĂ©ta-analyses sont mitigĂ©s et la comprĂ©hension de l’efficacitĂ© des programmes demeure toujours lacunaire, notamment en raison de l’hĂ©tĂ©rogĂ©nĂ©itĂ© des difficultĂ©s prĂ©sentĂ©es par les familles et de l’utilisation d’indicateurs de changement majoritairement centrĂ©s sur le fonctionnement de l’adolescent(e). La prĂ©sente thĂšse vise Ă  pallier ces limites en s’intĂ©ressant aux processus cliniques au cƓur de ces programmes, c’est-Ă -dire Ă  ce qui prend place avant et pendant l’intervention et Ă  la relation entre ces processus et les rĂ©sultats de l’intervention. Le premier article de la thĂšse, intitulĂ© Intensive family intervention programs: tailoring intervention to family clinical profiles et publiĂ© en 2020 dans la revue Children and Youth Services Review, vise Ă  identifier des profils cliniques de familles bĂ©nĂ©ficiant d’un programme d’intervention familiale intensive et Ă  les comparer en fonction de l’intervention reçue. RĂ©alisĂ©e Ă  partir de caractĂ©ristiques individuelles de l’adolescent(e) et de caractĂ©ristiques familiales de 237 familles ayant bĂ©nĂ©ficiĂ© du programme CAFE, les analyses de profils latents ont menĂ© Ă  l’identification de quatre profils cliniques distincts. Les analyses de comparaison ont permis de mettre en lumiĂšre des diffĂ©rences concernant l’intervention reçue par ces familles et signalent un certain manque d’ajustement de l’intervention aux profils cliniques des familles. Le second article de la thĂšse, intitulĂ© Intensive family intervention programs: Evolution of families with different clinical profiles et soumis en 2021 Ă  la revue Family Process visait quant Ă  lui Ă  examiner l’évolution des jeunes et des familles prĂ©sentant des profils cliniques distincts Ă  la fin de l’intervention ainsi qu’une annĂ©e suivant l’entrĂ©e dans le programme. Les rĂ©sultats montrent que l’ensemble des familles Ă©voluent positivement, tant sur le plan des comportements extĂ©riorisĂ©s de l’adolescent(e) que sur le plan du fonctionnement familial. Les rĂ©sultats montrent Ă©galement que les changements se maintiennent aprĂšs la fin de l’intervention. Les familles prĂ©sentant un profil clinique sĂ©vĂšre semblent toutefois prĂ©senter une Ă©volution plus tardive sur le plan des comportements extĂ©riorisĂ©s de l’adolescent(e), soulignant l’importance d’ajuster les paramĂštres de l’intervention offerte aux profils cliniques des familles. Les rĂ©sultats de la prĂ©sente thĂšse contribuent Ă  l’avancement des connaissances en mettant en lumiĂšre la complexitĂ© des profils cliniques prĂ©sentĂ©s par les familles bĂ©nĂ©ficiant d’une intervention familiale intensive et en s’intĂ©ressant Ă  l’ajustement de l’intervention aux caractĂ©ristiques des jeunes et des familles, principe clĂ© de ce type de programmes. La prĂ©sente thĂšse contribue Ă©galement Ă  l’avancement des connaissances en allant au-delĂ  de l’efficacitĂ© gĂ©nĂ©rale des programmes et en portant un regard sur les processus cliniques et leur impact sur l’évolution des familles prĂ©sentant des profils cliniques distincts. Ces rĂ©sultats permettront d’amĂ©liorer les services offerts aux jeunes et aux familles bĂ©nĂ©ficiant des programmes d’intervention familiale intensive
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