La maladie de Huntington (MH) est une maladie autosomale dominante causée par une expansion de la répétition CAG codant pour une expansion de la polyglutamine dans le premier exon du gène Huntingtine (HTT). Ce gène code pour une protéine ubiquitaire dont la mutation entraine de graves symptômes moteurs, psychiatriques et cognitifs, dus à la dégénérescence spécifique des neurones GABAergique épineux moyens du striatum. Nous proposons d'utiliser le trans-épissage pour développer un vecteur de thérapie génique qui réduira significativement voir éliminera l'expression de la protéine mutée tout en restaurant un niveau physiologique de HTT normale dans les cellules affectées par la mutation du gène Huntingtine. Cette technologie est basée sur le remplacement de l'exon muté par un exon sans mutation pendant l'étape de maturation de l'ARNm. Du fait du caractère dominant de la mutation,l'efficacité thérapeutique nécessitera une réaction de trans-épissage très efficace capable de convertir une portion significative de pre-ARNm HTT mutés en en ARNm HTT normaux. Nous avons donc développé un système rapporteur fluorescent permettant la détection des évènements de trans-épissage afin d’identifier les séquences les plus performantes parmi une centaine de molécules candidates. Nous avons validé notre stratégie de criblage basée sur la fluorescence et réalisé le criblage sur plusieurs introns HTT (3, 9 et 20) qui ont démontré des zones favorables au trans-épissage. Une méthode de quantification directe et absolue du taux de trans-épissage a également été validée pour déterminer très précisément le taux de correction. L’ensemble de ce travail a permis de contribuer à la mise en évidence de la faisabilité du trans-épissage dans le contexte de la MH. / Huntington’s disease (HD) is an autosomal dominant genetic disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract in the first exon of the Huntingtin gene (HTT). This gene encode a ubiquitous protein in which mutation lead to severe motor, psychiatric and cognitive deficits and causes degeneration of specific neuronal populations, in particular the GABAergic medium spiny neurons of the striatum. We propose to use trans-splicing to develop a gene therapy vector that will significantly reduce or eliminate the expression of the mutant protein while restoring a physiological level of normal HTT in cells affected by the HD mutation. This technology is based on replacement of the mutated exon by a normal version during the mRNA maturation process. HTT mutation being dominant, therapeutic benefits necessitates a highly efficient trans-splicing reaction that would convert a significant proportion of mutant-HTT pre-mRNA into normal HTT mRNA. For this purpose, we developed a fluorescent reporter system enabling the detection of trans-splicing events in high content screening in order to identify the most potent trans-splicing sequences among hundreds of molecules. We validated our fluorescent screening strategy and implement trans-splicing screening on 3 HTT introns (3, 9 and 20), in which we demonstrated the presence of hotspot promoting trans-splicing reactions. A direct and absolute quantification method was also validated to accurately assess the correction rate. Overall, this work generated additional evidences of trans-splicing feasibility in HD.

The aim of this paper is to understand how trans people who write and read fanfiction about gender euphoria create meaningful writing processes, contextualize community, and orientate themselves in the world by telling stories about gender euphoria and related emotional experiences. I have conducted interactive chat interviews with four study participants and have, as a way of using an autoethnographic research method, included my own narratives as part of the material. Thus, the material used in this study consists of transcripts of collective sensemaking and discussions about differences and similarities in the experiences that the study participants and I tell each other about. I have analyzed the material using queer phenomenology and affect theory. I have found that the study participants have both varied and similar experiences of finding representation, of translating their emotions into actions, and of (re)shaping what it is that they, as trans people, can do and what narratives they can tell and experience.

This theoretical thesis is focused on mapping and comparing the leading psychological transpersonal approaches to the conception of development of consciousness of an individual. This research is exploring the theory of Ken Wilber, Michael Washburn and Stanislav Grof also paying attention to the main disagreement among them regarding the confusion of prepersonal and transpersonal spheres of consciousness. This disagreement is further elaborated in an effort to find a conclusion and to seek for an integrative theory. The theories are compared with regard to the findings about psychedelic experience. The psychedelic experience is psychologically elaborated with emphasis on the current scientific knowledge in the field and their embedding in the context of the developmental theories of consciousness taking the effort of unravelling the pre/trans fallacy and the clinical implications into account. KEYWORDS Developmental theory, consciousness, transpersonal, psychedelics, pre/trans fallacy

Yes / If a prosthetic foot creates resistance to forwards shank rotation as it deforms during loading, it will exert a braking effect on centre of mass progression. The present study determines whether the centre of mass braking effect exerted by an amputee's habitual rigid ‘ankle’ foot was reduced when they switched to using an ‘Echelon’ hydraulic ankle–foot device. Nineteen lower limb amputees (eight trans-femoral, eleven trans-tibial) walked overground using their habitual dynamic-response foot with rigid ‘ankle’ or ‘Echelon’ hydraulic ankle–foot device. Analysis determined changes in how the centre of mass was transferred onto and above the prosthetic-foot, freely chosen walking speed, and spatio-temporal parameters of gait. When using the hydraulic device both groups had a smoother/more rapid progression of the centre of pressure beneath the prosthetic hindfoot (p ≤ 0.001), and a smaller reduction in centre of mass velocity during prosthetic-stance (p < 0.001). As a result freely chosen walking speed was higher in both groups when using the device (p ≤ 0.005). In both groups stance and swing times and cadence were unaffected by foot condition whereas step length tended (p < 0.07) to increase bilaterally when using the hydraulic device. Effect size differences between foot types were comparable across groups. Use of a hydraulic ankle–foot device reduced the foot's braking effect for both amputee groups. Findings suggest that attenuation of the braking effect from the foot in early stance may be more important to prosthetic-foot function than its ability to return energy in late stance.

Thesis advisor: Shih-Yuan Liu / Thesis advisor: Amir H. Hoveyda / Chapter 1. Senphos–Palladium-Catalyzed cis-Carboboration of Internal 1,3-Enynes with Carbon–Bound Boron Enolates: Reaction Development and Mechanistic Analysis. A new family of carbon-bound boron enolates (C–boron enolates) that are created through a kinetically controlled halogen exchange process between B–chlorocatecholborane and silylketene acetals is presented. These C–boron enolates are demonstrated to activate 1,3-enynes substrates in the presence of a Senphos-Pd complex to achieve carboboration reaction of an alkyne unit. This carboboration reaction produced highly substituted dienyl boron building blocks in high site-, regio-, and diastereoselectivity. A combined experimental and computational study of this carboboration reaction by Density-Functional Theory (DFT) calculations, 31P NMR study, kinetic study, Hammett analysis and Arrhenius/Eyring analysis will also be described. Mechanistic study supports a syn outer-sphere oxidative addition mechanism featuring a Pd-π-allyl intermediate followed by coordination-assisted rearrangement instead of the conventional inner-sphere β-migratory insertion mechanism. Chapter 2. trans-Hydroalkynylation of Internal 1,3-Enynes Enabled by Cooperative Catalysis. A trans-hydroalkynylation reaction of internal 1,3-enynes enabled by a cooperative catalysis system that comprises of Senphos–Pd complex, tris(pentafluorophenyl)borane, copper(I) bromide, and 2,2,6,6-tetramethylpiperidine, is described. The tris(pentafluorophenyl)borane as Lewis acid catalyst is shown to promote the reaction involving the emerging outer-sphere oxidative reaction step. This hydroalkynylation reaction affords the cross-conjugated dieneynes that serve as versatile synthons for organic synthesis. The photophysical properties of these cross-conjugated dieneynes depend on the position of electron donor/acceptor substituents along the conjugation path, as characterized by UV–vis absorption and emissions spectroscopy. Chapter 3. Senphos–Palladium/B(C6F5)3-Catalyzed trans-Hydrothiolation of 1,3-Enynes: Reaction Development and Mechanistic Analysis. A trans-hydrothiolation reaction of 1,3-enynes enabled by a cooperative catalysis system that comprises of Senphos–Pd complex and tris(pentafluorophenyl)borane is detailed. The tris(pentafluorophenyl)borane is shown to alter the reaction pathway, leading to a trans-addition product over cis-addition one. Experimental mechanistic study that includes 31P NMR, kinetic study, kinetic isotope effect (KIE) study, Hammett analysis, is consistent with a cooperative activation mechanism that features an outer-sphere protonation step. / Thesis (PhD) — Boston College, 2023. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Under de senaste 10 åren har gruppen som sökt hjälp för könsdysfori ökat. Personer med könsdysfori är särskilt utsatta för att utveckla psykisk ohälsa jämfört med befolkningen i övrigt. Det saknas dock kunskap om deras närståendes upplevelser. Den här studien är del av svenska könsdysforistudien, SKDS. Syftet med studien var att i en svensk kontext undersöka närståendes upplevelse av att leva nära en person som genomgår utredning och behandling för könsdysfori. Utifrån semistrukturerade intervjuer med elva närstående tolkades materialet genom induktiv tematisk analys. Analysen visade att de närstående upplevt att relationen fördjupats genom processen. Oavsett varierande reaktioner initialt har samtliga närstående landat i en vilja att genom fördjupad kunskap stå upp för den vårdsökande. För många har processen känts tung och ensam. Samsjuklighet och minoritetsstress har bidragit till ökad komplexitet och tyngd. Man har också hittat kraft i den gemensamma kampen. En slutsats är att den icke-dömande hållningen och oreserverade acceptansen hos de närstående, inte i samma grad återspeglats i internationella studier. En ytterligare slutsats är att de närstående utgör en viktig resurs i den vårdsökandes möjlighet till ett gynnsamt behandlingsutfall och att de närstående behöver uppmärksammas och erbjudas stöd för att själva kunna vara ett stöd. / Delstudie till Svenska könsdysforistudien (SKDS)

The objective of the study was to examine the effects of trans-9-octadecenoic acid (elaidic) and trans-II-octadecenoic acid (trans-vaccenic) on uptake and alteration of exogenous fatty acids by mouse mammary epithelial cells. Cells from a subclone of the COMMA-D cell line were plated on uncoated plastic petri dishes and grown to confluence. Supplemental fatty acids bound to bovine serum albumin were added to the medium applied to the confluent cell cultures. Treatments included 200 JlM octadecanoic acid (CI8:0) as a control and 100 JlM CI8:0 with one of the following JlM ratios of cis-octadecenoic acid (cis-CI8:I) to elaidic or trans-vaccenic: 100:0, 75:25, 50:50, 0:100. In addition, all treatments were conducted with or without lactogenic hormone supplementation. The cellular protein to DNA ratio and total amount of fatty acids per mg protein were decreased (P < .05) by addition of lactogenic hormones. In treatments without hormone supplementation, however, the total amount of cellular fatty acids per mg protein was decreased (P < .05) by addition of either trans-CI8:I isomer. Results indicated a significant (P < .05) relationship between the concentration oftrans-C18:1 in the media and uptake of trans-C 18: 1 isomers, and retroconversion of trans-C 18: 1 to trans-C 16: 1. The slopes of the lines for cellular C16:0, cis-C16:1, and cis-CI8:1 were less (P < .05) than zero as concentration oftrans-CI8:1 in the media increased. However, trans-CI8:1 isomers did not influence the proportion of polar and nonpolar lipids synthesized by the cells. It appears that trans fatty acids may depress milk fat output by decreasing de novo fatty acid synthesis and cis-C 18: I content. / Master of Science

An essay and short story collection about rebirth and being trans and neurodivergent. The essays and stories cover the entire length of my MA, but are mostly written before I came out as trans and edited after. The arc follows this discovery as well as the discovery of my writing following more experimental means including the twisting and playing with the braided essay, the introduction of essaying moves to fiction forms, and moving from what I thought was about death to what I realized I was writing all along about rebirth.

The purpose of this transcendental phenomenological study was to explore Black transgender men's experiences navigating systems of racism and transphobia. To this end, I utilized a critical race theory and intersectionality theory framework to answer the following question: What are Black transgender men's experiences with power, privilege, and oppression? The ten Black transgender men and transmasculine people who participated in this study provided detailed and moving accounts of their experiences with systems of oppression. Six major themes were prominent throughout participant narratives: (1) developing an empowered view of self, (2) navigating double consciousness, (3) having a target on your back, (4) strategies of resilience, (5) culture of silence, and (6) finding quality care. Overall, participants offered insight and keen awareness of their intersecting racial and gender identities, as well as speaking intimately about how the shift from societal perceptions and identification as a Black woman to a Black man impacted their sense of self and views of the world. Additionally, implications and conclusions drawn from the stories of participants offer recommendations for counselors, mental health professionals, practitioners, and programs to consider implementing to provide culturally responsive and competent care to Black transgender men.

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