29 research outputs found
RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Infectious Diseases following peer review. The version of record Yiyao Huang, Ahmed Abdelgawad, Andrey Turchinovich, Suzanne Queen, Celina Monteiro Abreu, Xianming Zhu, Mona Batish, Lei Zheng, Kenneth W Witwer, RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology, The Journal of Infectious Diseases, 2023;, jiad563, https://doi.org/10.1093/infdis/jiad563 is available online at: https://doi.org/10.1093/infdis/jiad563. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected]. This article will be embargoed until 12/11/2024.Background
Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in human immunodeficiency virus (HIV) CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation.
Methods
Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs).
Results
Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection.
Conclusions
RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.This work was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (grant numbers DA040385 and DA047807 to K. W. W.); by 2 pilot grants awarded to Y. H. through the Johns Hopkins National Institute of Mental Health (NIMH) Center (supported by National Institute of Mental Health MH075673) and the Johns Hopkins University Center for AIDS Research (supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases P30AI094189-01A1); and the National Science Foundation (grant number 2244127 to M. B.). The Witwer laboratory is also supported in part by National Cancer Institute/Common Fund (grant number CA241694); National Institute of Allergy and Infectious Diseases (grant number AI144997); National Institute of Mental Health (NIMH) (grant number MH118164); and the Johns Hopkins University Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease. Samples used in this study were derived in part from research supported by National Institutes of Health (NIH) (grant number U42OD013117 to Johns Hopkins pigtailed macaque breeding colony); National Institute of Neurological Disorders and Stroke (grant number NS089482 to Joseph L. Mankowski); and National Institute of Mental Health (NIMH) (grant number MH070306 to Janice E. Clements)
Derrida and postmodernity: At the end(s) of history
No full textThis thesis erects and defends the proposition that Jacques Derrida's readings of 'metaphysics in deconstruction' and his raising to theoretical consciousness of the 'differential matrix', have the capacity to inaugurate a 'brave new world' in this postmodern 'age of the aporia'. Beginning with an examination of Derrida's readings of Husserl and Saussure, it is argued that the radical historicity uncovered here qua an originary synthesis of language, time and the other, opens the possibility for greatly more democratising and emancipating self-creations and human solidarities to be thought. In terms of 'self-creations', and borrowing from the work of Elizabeth Deeds Errnarth, Chapter Two follows Derrida as modernity's sovereign subject and its 'History' are dis-placed by an absolutely affirmative postmodern subjectivity whose axiom might be 'I inherit, therefore, I am ... yes, yes ... ' Construed through his deconstructive reading of Kant, Derrida shows the way in which this postmodern subjectivity without alibi, makes of us all (like it or not, know it or not) resistance fighters, so many singularities existing in constant tension with all normalising/totalising tendencies (social, economic, techno-scientific, political, legal etc ... ) which profess to know the secret. Turning to co-extensive 'human solidarities', Chapter Three subsequently demonstrates the way in which Derrida's call for a 'New International', orientated through a 'new figure of Europe', enables us to imagine new polysemic communities (local, national, international) founded on the 'aporia of the demos', a 'foundation' that construes its hyper-relativity as a positive (ethico-political) condition of decision in terms of a radical responsibility (on an individual and communal level) for the moral/aesthetic decisions we make. It is thus that I will argue that Derrida's vision for a 'new world order' is born out of an aporetic condition which is both a risk and a chance of both the best - and the worst - happening; as someone who shares Derrida's desire for a fairer, freer, more peaceful world, one respectful of difference and otherness, I believe this to be a 'poker like gamble' well worth taking. Chapter Four offers a comparative analysis between the work of Jacques Derrida and Jean Baudrillard, two theorists counter-signing differently many of the 'same' discourses/ traditions/cultures/languages, etc ... to which they are both heirs. The chapter examines their respective 'quasi-philosophies of the limit', together with their differing conceptions of the issues surrounding globalisation and universalisation, as well as Baudrillard' s elevation of America (as opposed to Europe) as the exemplary site of resistance against the dangers of totalisation in 'postmodem' societies. The central argument here, in line with my previous remarks, is that Derrida's thought arguably remains 'the best' way to navigate the postmodem condition and the challenges it produces. The originality of this thesis lies in two main areas, the first having to do with my presentation and conception of Derrida's oeuvre and the second having to do with the comparisons made in this study between Derrida and Ermarth and Derrida and Baudrillard. In terms of the former, I offer what I consider to be a unique, sustained, in-depth analysis of the 'development' (on a theoretical and practical level) of the thematics of 'radical historicity' and of 'post-historical man' - effectively the development of Derrida's quasi-philosophy of history- from his earliest works so that they can be seen to inform his later intervention(s) in what are conventionally understood as ethical and political matters; transforming this understanding in the process and, after the end of history's ends (upper case, lower case and the totalising 'history of meaning' per se), quite literally and radically changing the way we see what we call 'the world'. For while in the conventional literature Derrida's politics come late, I argue here that his indeed later political work is but an emphasis of constant political thematics acting as a leitmotif from beginning to end. Turning to the latter, in terms of the comparisons I make - first between Derrida and Ermarth in Chapter Two and more especially between Derrida and Baudrillard in Chapter Four - the claim to originality lies in the fact that there is no comparison of any note or depth in the literature between these thinkers; nothing that compares Derrida's 'affirmative postmodem subjectivity' and its 'inheritance' with Ermarth's 'rhythmic time' and 'muIti-level consciousness', and nothing comparing Derrida's corpus - specifically his optimistic emancipating and democratizing hopes for the future - with Baudrillard's more pessimistic conceptualization of 'simulation society' and the loss of our European universal values under the hegemonic, globalising movement of the 'American model'. The aim of these two comparisons is to support my claim that Derrida's historico-political position is the 'best' way of essaying the quasi-ground of an in(different) politics in such a way that it keeps the future open to what he calls a 'better world' to come, a world without ends
WM2008 Paper WM-8293
No full textAbstract #8293 Glass performance exceeded all disposal performance criteria. A previous issue with MIS containment was successfully resolved in FS-38D, and the ICV™ melter was integrated with a full-scale, 10,000-liter dryer. This paper describes the rationale for performing the test, the purpose and outcome of scale-up tests preceding it, and the performance and outcome of FS-38D
iWaandr: Life's Best Experiences. Shared.
No full textabstract: iWaandr is a travel platform that allows users to find and share unique experiences. It will be a website that users can find on the internet. Every user will be able to post their own experiences on the platform along with a description, important information, and a rating.
The problem we are trying to solve is that it still takes hours to search for and find unique non-touristy experiences around the world. At a time when people can use their smartphones to have a car show up to their doorstep in minutes, it is unacceptable that it still takes hours to find an non-touristy experience on the internet.
Our value proposition is that users will be able to be anywhere in the world and be able to find an authentic, non-touristy experience that interests them. iWaandr is the most complete experience discovery tool, providing the largest collection of unique and personal experiences around the world.
Our competition is the large incumbent travel and review companies like TripAdvisor and Airbnb. There are also less established competitors that see a similar gap in the market like Mapify and Cool Cousin. We also have niche competitors that are only focused on outdoor activities like AllTrails and Outbound Collective. Google and blogs would also be competitors because people search on Google for unique experiences.
Our innovation is that we are focusing on creating unique content while our competitors are focusing on new ways to display the same content. Our advantage isn’t in a feature we created because a company with more resources could easily copy it. In order to create unique and useful content, we had to figure out a way for users to intuitively and easily post an experience with as much relevant information as possible. This involved a lot of thought into our posting process. We believe our posting process allows users to consistently post unique and informative content.
The technology we are implementing is very similar to the FERN technology stack of Firebase as a database, ExpressJS and NodeJS as backend frameworks, and ReactJS as the front-end programming language. We chose this technology stack because it allows our platform to stay lean, and be efficient with data. This allows the platform to have increased performance and lower costs
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
No full textFull author list omitted for brevity. For the full list of authors, see article.The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points
Durability evaluation of glasses to immobilize Fukushima (1F) secondary waste using ASTM C1220 (MCC-1) testing
No full textFollowing the 2011 accident at the Fukushima Daiichi Nuclear Power Plant (1F), contaminated water was treated to remove radionuclides. The water treatment processes generated ∼4500 m3 of secondary wastes including sludges and spent media. Vitrification using GeoMelt® In-Container Vitrification (ICV)™ is a technology being considered for treatment of these wastes. ICV is well suited due to its ability to process a broad range of wastes at high temperatures without the need to pour glass which results in high waste loading and high chemical durability. The objective of this study was to formulate glasses suitable for ICV processing of 1F secondary wastes with high chemical durability. Thirty-six glasses were formulated for different 1F secondary waste blends with loadings ranging from 60 to 92 wt%. Materials Characterization Center durability test number 1 (MCC-1 – ASTM C1220) responses were measured for the glasses in deionized water at 90 °C for 7 to 365 days. Their MCC-1 responses were equal or below those for well-characterized reference waste glasses from US, Japan, and France demonstrating their high durability. The 1F glass MCC-1 data were combined with literature data from US, French, and Japanese high-level waste glasses and a model was fitted to MCC-1 durability response as a function of glass composition. Component effects on MCC-1 responses were discussed in context of glass alteration theory
A comprehensive review of relationships, social isolationism and adolescents
No full textPlan BAs one looks at life styles and attitudes we are able to look no further then our adolescents and their displaying of behaviors. Society is developed and maintain by individual behaviors. As history has indicated in the past changes can either assist in a cultures present or causing stagnation and slow death. This is true of today’s life styles for our adolescents, are taking greater risk and with higher potential for violence towards themselves as well as to others. As a society we the adults have become numb or indifferent to the events that are becoming almost everyday events, such as school shooting, and road rage. This increase in negative and destructive behavior by its citizens in the past has lead to a breakdown and rejection of a society. Looking at the increase in the aggressive behavior our adolescents are displaying the intent is for society to look at what can be done now to make changes for the future. What is it that adults, communities, education, and adolescence themselves can do in reducing hostility and developing an open and trusting relationship with one another. What steps can be taken now in hopes of insuring a better society for further youth
