EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 molar ratio of 5.4 and 0.37, respectively, with no difference in CB1 receptor expression. To test the hypothesis that CRIP1a modulates CB1 receptor signaling, G-protein and effector activity were examined with and without full, partial and inverse agonists. [35S]GTPgS binding, which measures G-protein-coupled receptor (GPCR)-mediated G-protein activation, showed that CRIP1a inhibited constitutive CB1 receptor activity, as indicated by the decreased effect of the inverse agonist SR141716A. CRIP1a also decreased CB1 receptor-mediated G-protein activation by high efficacy agonists, whereas moderate and low efficacy agonists were unaffected. In experiments varying Na+ concentration, CRIP1a decreased spontaneous G-protein activation at low Na+ concentrations, where spontaneous GPCR activity is highest. This effect was eliminated by pertussis toxin pre-treatment, indicating that CRIP1a only inhibits GPCR-mediated activity. To determine whether CRIP1a modulates receptor adaptation, hCB1-HEK (±CRIP1a) cells were pretreated with WIN or THC. Both ligands desensitized CB1 receptor-mediated G-protein activation, but desensitization was unaffected by CRIP1a. In contrast, CRIP1a attenuated downregulation of CB1 receptor binding sites by WIN, but not THC. Downstream, CRIP1a attenuated constitutive CB1 receptor-mediated inhibition of cAMP, as indicated by elimination of SR141716A-stimulated cAMP, without affecting agonist-induced cAMP inhibition. Constitutive inhibition was not due to endocannabinoids because LC-ESI-MS-MS did not detect endocannabinoids in hCB1-HEK (±CRIP1a) cells. To determine whether effects of CRIP1a were conserved among cell types, Chinese Hamster Ovary cells expressing CB1 receptors were stably co-transfected with CRIP1a, and had a CRIP1a/CB1 receptor molar ratio of 15 and 1900 with and without CRIP1a over-expression, respectively. In this model, CRIP1a inhibited constitutive CB1 receptor-mediated G-protein activity, but activation by agonists was enhanced, suggesting CRIP1a effects were dependent on stoichiometry of CRIP1a/CB1 receptor or cell type. Overall, these results indicate that CRIP1a decreases constitutive CB1 receptor activity, modulates agonist efficacy, and inhibits CB1 receptor downregulation, in a ligand- and cellular environment-dependent manner.

Denna studie baseras på kvalitativa semistrukturerade djupintervjuer med personer med olika fysiska funktionsnedsättningar om deras upplevelser och erfarenheter om funktionsnedsättningar, sexualitet och genusgörande. Kategorin funktionsförmåga är i många diskurser omarkerade. I det icke uttalade om kroppars olika förmågor förväntas och blir en funktionsfungerande kropp norm. Min studie grundar sig på ett teoretiskt samarbete där Robert McRuer’s cripteori utgör referenspunkten. Studiens syfte är att synliggöra idéer om hur en normal kropp bör se ut, bete sig, göra sexualitet och genus. Jag visar på hur detta påverkar kroppar och göranden som bryter mot dessa normativa idéer. Genom att lyfta fram informanternas berättelser avslöjas och synliggörs förhindrande, förminskande normer och diskurser vars konsekvenser många gånger bidrar till tal om könslöshet och asexualitet. Jag visar med informanternas berättelser på ett möjligt motstånd mot dessa normer och diskurser. I deras berättelser synliggörs den normata kroppen och vad som anses vara respektabel sexualitet. Vilka har möjlighet att göra anspråk på den? Informanterna visar på motaktioner som manifisteras genom att göra sig attraktiv, feminin/maskulin, sexuell och begärlig. Till syvende och sist handlar det om vilka kroppar som har rätt att synas och vara sexuella. / This thesis is based on qualitative semi-structured interviews with persons who have physical impairments and their knowledge and experience regarding disability, sexuality and gender. In many contexts physical ability remains unmarked. In the context of body abilities, a function able body is the norm. The study is grounded in Robert McRuers crip theory. The aim of the thesis is to investigate the ideas of how a normal body should look like, behave and express its sexuality and gender. How these ideas may influence the bodies and actions that try to challenge the norm. By focusing on the informants stories, I reveal and highlight, belittling norms and discourses that render various subjects as asexual and genderless. I show with these stories a possibility for resistance against the norm and these discourses. In their stories they make references to what they think is respectable sexuality and the normate body. Who has the right to claim that body? The informants take action against the norm by making themselves attractive, feminine/masculine, sexual and acquisitive. In the end it all comes down to which bodies that have the right to express themselves as sexual.

The aim for this study is to examine the educational material ​Sex- och samlevnadsundervsining i särskola (2014), directed to teachers in schools for children with disabilities. The material is produced by Skolverket (the Swedish National Agency for Education) and aim to support teachers in their sexuality education classes. This study examines how the material manages discourses regarding sexuality, heteronormativity and gender for students with disabilities. The material is also being compared with another educational material by Skolverket aimed for teachers in primary school. It is a qualitative study that is conducted with the method of a critical discourse analysis, through the perspective of crip theory and queer temporality, both developed within queer theory. The result of the studies shows, among other things, that Skolverket applies a norm-critical perspective in the material through a normats point of view, and by that means maintains the dichotomy between normat and disabled. Skolverket is also contributing to discourses regarding social norms, such as what is “right” and “wrong”, which can limit the students from exploring their sexuality.

The aim of this master’s thesis is to study how a group of people diagnosed with autism spectrum disorder experience a visit to the library. By interviewing them I hoped to hear their thoughts on noise, lighting and the over all library environment. Did the informants get a fair treament by the library staff or did they feel stigmatized? The thesis is also aiming to expose how accessible the libraries’ websites are. Two librarians shared their insights about accessibility from the library in which they work. The interview showed there are still many aspects that need to improve until the library is autism friendly. The study shows that the informants prefer a silent library compared to a noisy one. They did not experience any stigmatization in the library. The informants use the digital services offered by the library in order to renew their books and to request new ones. However, the websites are not customized for people with Austism spectrum disorder. The informants main concern when visiting the library are loud noise and insufficient signs. This study is a two years master’s thesis in Library and Information Science.

This sandwich thesis initiates a dialogue to examine connections and departures between new media studies, platform studies, critical digital race studies, critical disability studies, and feminist data studies. The manuscript presents four research papers that traverse issues regarding ableist platform governance, algorithmic visibility, and crip/neuroqueer digital cultural production. My theorizing of crip data seeks to interrupt hegemonic Western and Eurocentric conceptualizations of what is (not) valued and who (does not) holds power within platform spaces. Moreover, an intersectional focus on disability and race interrogates the ways technoableism (Shew, 2020) and algorithmic oppression (Noble, 2018) collectively animate the creation, development, and use of platforms and other new media technologies. I introduce crip data studies as an interdisciplinary academic and activist theoretical framework that counters the dominance of Western and Eurocentric ideologies that inform a digital platform’s algorithmic infrastructure, governance, and cultural production. I utilize the sandwich thesis model to examine the ways crip data can support critical/cultural investigations about platforms, power, disability, race, and culture through various case studies. In Chapter 1, I assess the relationship between race, disability, and bias in platform content moderation. Chapter 2 proposes neuroqueer practices for new media production and disability engagement that do not reproduce techno-solutionist measures in mediating neuroqueer self-expression and digital relationality. Chapters 3 and 4 communicate the generative departures of crip and neuroqueer platform use as a mode of hosting cultural production. In sum, this thesis engages with enmeshed inquiries regarding disability, race, and ideological value to respond to the following provocation: Is another platform– one beyond ableist, racist, and colonial bias– possible? / Dissertation / Doctor of Philosophy (PhD) / This thesis introduces crip data studies as a theoretical practice that challenges how dominant Western, Eurocentric conceptualizations of disability and race inform governance and cultural production on digital social platforms. I invoke crip, a subversive reclamation that reframes disability as a political and cultural identity, to disrupt the erasure and devaluation of disability within digital platforms. Through theorizing crip data, I reconfigure the disabled user and creator to investigate the significance of technological bias in shaping platform economies, politics, and creative engagement. The thesis project has two goals. First, crip data reveals how offline biases animate a platform’s algorithmic infrastructure and user interactions. Crip data also amplifies the creative, strategic practices shaping digital disability cultural production on social sharing and content creation platforms. In doing so, the manuscript demonstrates how crip data offers potentialities for intersectional readings beyond platformed mediations of ableism, racism, and coloniality.

<p>The aim of this study was to examine the possibilities to enter the regular labour market for pupils and young adults with intellectual disabilities. The method used is tape-recorded qualitative interviews with; Two pupils with intellectual disabilities, studying the last year at a special school. Two young adults with intellectual disabilities, former pupils at a special school and at the moment in search of work at a Public Employment Service office for young adults with disabilities. Furthermore were interviews made with two professionals, one student counsellor at a special school and one representative at a Public Employment Service office for young adults with disabilities. For analysing the empirical data, Iris Marion Young's theory about Five Faces of Oppression, Crip theory and Dalrymple and Burkes theory about empowerment was used. The results showed difficulties in enter the labour market for these young adults and wishes to be able to support themselves financially by a regular work. The aim of the welfare system is to help people with intellectual disabilities through for example special schools, vocational training and wages benefits. These efforts are not really helping but are rather increasing the disabilities and the following discrimination on the labour market.</p>

The aim of this study was to examine the possibilities to enter the regular labour market for pupils and young adults with intellectual disabilities. The method used is tape-recorded qualitative interviews with; Two pupils with intellectual disabilities, studying the last year at a special school. Two young adults with intellectual disabilities, former pupils at a special school and at the moment in search of work at a Public Employment Service office for young adults with disabilities. Furthermore were interviews made with two professionals, one student counsellor at a special school and one representative at a Public Employment Service office for young adults with disabilities. For analysing the empirical data, Iris Marion Young's theory about Five Faces of Oppression, Crip theory and Dalrymple and Burkes theory about empowerment was used. The results showed difficulties in enter the labour market for these young adults and wishes to be able to support themselves financially by a regular work. The aim of the welfare system is to help people with intellectual disabilities through for example special schools, vocational training and wages benefits. These efforts are not really helping but are rather increasing the disabilities and the following discrimination on the labour market.

Den genusvetenskapliga forskningen uppmärksammar idag flera olika maktordningar och intra-aktionen dem emellan. Aspekten ålder är emellertid relativt förbisedd, och vuxna och vuxenhet en omarkerad norm. I denna uppsats undersöker jag med utgångspunkt i queerteori, cripteori, intersektionalitet och kritisk åldersforskning föreställningar och antaganden i relation till kategorierna barn och vuxna i fem svenska tidningar/tidskrifter. Min uppsats visar att aspekten ålder intra-agerar med andra maktordningar i konstruktionen av både barn och vuxna. Vuxenperspektivet är i de undersökta tidningarna i princip ensidigt och synen på ålder är övervägande essentialistisk. Vuxna förstås som naturligt överordnade barn, vilka avhumaniseras och konstrueras som vuxnas rättighet eller egendom, eller som en förlängning av vuxenkroppen. Vuxenhet kopplas till reproduktion och yrkesarbete (på heltid) och vuxnas solidaritet bör enligt den hegemoniska diskursen ligga hos arbetsgivare och andra vuxna, inte hos barn. / Even though several researchers in gender studies of today are concerned with other central organizing aspects than gender, the social category age is disregarded. When it comes to age the naturalized norm in gender studies is the category the adult. In this thesis I investigate assumptions concerning the two age categories children and adults in five different newspapers and magazines, using an intersectional perspective and a queer theoretical framework. My investigation shows that the category age intra-act with other power structures in the construction of both children and adults. The adult perspective is more or less one-sided, and the view on age is primarily essentialistic. Adults are considered naturally superior, while children are dehumanized and constructed as the right and property of adults. Adultness is primarily linked to reproduction and (full-time) professional work, and adults should according to the hegemonic discourse be loyal to employers and other adults, not to children.

In this paper, I begin the first steps towards developing more ethical methods for designing for users with ADHD by investigating what needs stakeholders have when interacting with technology. Current interaction design projects concerned with ADHD are largely focused on children—ignoring adults with ADHD. Their aims and methods are problematic, potentially harmful, and erase experiences of those with ADHD by excluding them from the design process. These projects treat the ADHD community as a list of symptoms to be fixed by training behaviors—a practice that has been demonstrated to cause harm. Influenced by the Crip Technoscience, Neurodiversity, and Self-Advocacy movements and utilizing participatory/co-design methods I investigate the needs of users with ADHD by engaging with them throughout the process, ultimately leading to the development of preliminary guidelines for designing for ADHD accessibility which are presented in this paper alongside design examples and discussion of possible future work.

Stadsplanering och arkitektur har traditionellt sett prioriterat visuella värden i staden över andra sinnliga upplevelser. Synen dominans tillsammans med normen able-bodiedness ”den friska kroppen” inom yrkesgruppen gör att personer med blindhets erfarenheter och upplevelser blir exkluderade från samtalet om stadens utformning. Det bidrar också till en exkludering i staden genom att den bebyggda miljön i många fall inte är utformad efter deras behov. Personer med blindhets behov hanteras istället som tillgänglighetsåtgärder i ett senare skede och på så sätt framställs som något som skiljer från ”normalt” yrkesutövande. Denna studie studerar problematiken från en annan synvinkel. Här undersöks hur kunskap från personer med grav synnedsättning som inte huvudsakligen använder synen för orientering eller upplevelser av staden kan komma till nytta för stadsutvecklingen i stort. Syftet är att undersöka möjligheten att ta fram metoder som kan hjälpa till att synliggöra sinnliga upplevelser i staden. Människor har olika kroppsliga förmågor som påverkar hur vi använder våra sinnen och därför kan städer med olika sinnliga upplevelser bli mer anpassade för fler. Metoderna kan bidra till en mer inkluderande stad men även en mer variationsrik upplevelse, för alla oavsett funktionsförmåga, detta med större valfrihet och fler alternativ. Studien är både utforskande och ifrågasättande av subjektiviteterna ability och disability. Slutsatsen ger inte något konkret svar/lösning utan undersökning syftar till att synliggöra problem inom stadsplanering för att sedan vända dessa till möjligheter. Studien bidrar med metoder som kan hjälpa stadsplaneringen att reflektera över sinnliga upplevelser i staden och på så vis arbeta mot en mer inkluderande stad. Bidrar även med ett öppnare samtal om staden och utmanar normen om vilka som får vara med i utformningen av staden. Det finns ett behov av vidare forskning för att kunna använda kunskapen på en mer strategisk nivå, och en stadsplaneringen som vågar ta sig an de nya kunskaperna.