Traumatic brain injury (TBI) is the most common cause of mortality and disability in the younger (<50 years) Swedish population with an incidence rate of 20,000 cases per year. This thesis aims to increase the understanding of brain injury mechanisms, especially in a molecular and cellular context. Bone morphogenetic protein (BMP) signalling was examined in three genetically modified mice (two “loss-of-function”, one “gain-of-function”) exposed to TBI (controlled cortical impact, CCI) with CaMKII used as promoter for Cre-driven recombination in postnatal forebrain neurons. The mice survived, developed normally and did not show any obvious phenotypes except for an upregulation in Mtap2 mRNA in mice with impaired BMP signalling. Reactive Gfap and Timp1 mRNA expression measured using quantitative RT-PCR (qRT-PCR) was reduced in the mice overexpressing BMP signals. The BMP signalling pathway was further studied in cultured PC12 cells with BMP4 and NGF added. Egr3 expression was substantially increased by these growth factors. Blocking Egr or Junb functions reduced neurite outgrowth. TBI-induced mRNA expression changes in 100 selected genes in C57BL/6J mouse neocortex and hippocampus were measured using qRT-PCR at different time points post-injury. Several distinct gene clusters with similar expression patterns were identified. GeneChip analysis (Affymetrix) of the injured mouse neocortex at three days revealed 146 transcripts significantly upregulated, confirming and extending the qRT-PCR results. The findings demonstrate marked increases after injury among chemokine transcripts and activation of many genes involved in inflammation. In conclusion, the present study has revealed transcriptional changes in specific signalling pathways after brain injury. The results may help to identify novel targets for neuroprotective interventions after traumatic brain injury.

Cancers display heterogeneity in genetic profiles of the individual cancer cells and in the composition of different malignant and non-malignant cell populations. Such intra-tumor heterogeneity plays a role in treatment response and the emergence of resistance to cancer therapies. Approaches that address this complexity and improve stratification of patients for treatment are therefore highly warranted. Thus, the aims of this thesis were to further develop and apply in situ technologies for expression and mutation analyses of candidate cancer genes to gain a deeper understanding of cancer biology and to study intra-tumor heterogeneity. In paper I, we established and validated a procedure for scalable in situ hybridization of large gene sets in human formalin-fixed paraffin-embedded tissues for analysis of gene expression. This method was used in paper II for large-scale expression analysis of the tyrosine kinome and phosphatome, two gene families whose members are frequently mutated in many forms of cancers. Systematic, compartment-specific expression mapping at cell type resolution enabled us to identify several novel vascular markers that have gone unnoticed in bulk transcriptomic analyses. In papers III and IV, we used padlock probes for in situ mutation detection in single cells for studies of genetic intra-tumor heterogeneity. In paper III, multiplex detection and genotyping of oncogenic point mutations was demonstrated in routinely processed tissue materials, whereas in paper IV we further the application by demonstrating multiplex detection of fusion gene transcripts. Collectively, the work presented in this thesis employs in situ-based methods to obtain spatial resolution of gene expression and mutation patterns in normal and cancer tissues, thereby broadening our understanding of the cancer genome.

From the sexual preselection point of view, understanding sex determination/differentiation mechanisms in the bird is critical in both evolutionary and industrial applications. The chicken embryo provides an unique vertebrate model in the field of development biology. Morphological sex development in the chick gonad starts at 6.5 embryonic day (E6.5), however, genetic sex determination and development should occur earlier. In order to comprehend genes and their underlying mechanisms being involved in sex-determination/development during early embryogenesis, we not only made a male-subtract-female and a female-subtract-male cDNA library as early as embryonic day 3 (E3; Hamburger and Hamilton Stage 20), but also examined early transcripts related to male development in chicken embryo and their expression profiles in this study. A total of 89 and 127 candidates of male-development transcripts represented respectively for 83 known and 119 unknown non-redundant sequences, which were characterized in an E3 male- subtract-female complementary DNA library. In this study, thirty-five selected transcripts being validated by quantitative reverse transcription-polymerase chain reaction that the expression levels of 25 transcripts were higher in male E3 whole embryos than in females (P < 0.05). Notably, twelve of these transcripts mapped to the Z chromosome. At 72 weeks of age, twenty transcripts were expressed at higher levels in testes than in ovaries. Meanwhile, four transcripts were expressed at higher levels in brains of male than in brains of female chickens (P < 0.05). By using of methods of whole mount and frozen cross-section in situ hybridization, the expressions of riboflavin kinase (RFK), WD repeat domain 36 (WDR36) and EY505808 transcripts on E7 chicken male gonads were corroborated to be better than female gonads. This result was confirmed by using of western blotting analysis which also showed the expressions were specifically on gonads than other tissues. Treatment with an aromatase inhibitor formestane at E4 depicted the effect of the expression levels at E7 of the coatomer protein complex (subunit beta 1), solute carrier family 35 member F1, LOC427316 and EY505812 transcripts across both sexes (P < 0.05), which was similar to the observed gene expressions for both doublesex and mab-3 related transcription factor 1 gene. Additionally, the interaction effects of sex with formestane treatment were observed in 15 candidate male development transcripts (P < 0.05). This study demonstrated a panel of potentially candidate male development transcripts being identified during early chicken embryogenesis; some might be regulated by sex hormones.

Children with autism spectrum disorders typically experience language deficits in multiple areas, including form, content, and use. These children often receive speech therapy with individual sessions (one child and clinician), group sessions (several children), or a combination of both. Although research has deemed individual therapy successful, there is still debate regarding the success of group therapy, and there is virtually no literature examining a comparison between individual and group therapy. The current case-study investigated the relative effectiveness of individual versus group therapy for one six-year-old female with moderate autism spectrum disorder. The child underwent ten alternating therapy sessions of similar structure with consistent language targets during one academic semester. All sessions were transcribed using Systematic Analysis of Language Transcripts (SALT) conventions, and analyzed via the SALT program and Microsoft Excel t-tests. Results indicate that individual sessions yielded larger improvement with syntax and semantics, while group sessions produced greater progress with pragmatics and social skills, suggesting that a combination of both therapy types may be most beneficial. Social validation of group therapy also signified high parent satisfaction with overall growth during the semester. Implications of this study, as well as recommendations for future research and clinical practice are discussed.

Abstracts THE TAINT This is a memoir of Ray “Poss” Ide, a man who has carried the taint of a horrifying crime since he was seventeen years old─a crime he claims he did not commit. The crime was the rape of a fourteen-year-old girl. The Taint looks at the time leading up to his conviction for rape, including the years he spent in Westbrook Boys’ Reformatory and Boggo Road Gaol as a minor, and then his sentence served in NSW gaols with such inmates as Stephen Bradley, the man who kidnapped and murdered Graham Thorne, and the bizarre but rather likeable Dave Scanlan, known for his exploits as “the Kingsgrove Slasher”. In prison, Scanlan encouraged him to become an elite sportsman and released, Poss was recruited by Canterbury Eels football team; but just on the point of making a name for himself in Sydney, someone discovered that he had been gaoled for rape, and humiliated, he left the team. He moved back home to Queensland via Grafton, NSW (where he met and later married the Jacaranda Queen) and continued his sporting career, but never again in the Big League. He became the Manager of the Waterside Workers’ Club and helped prevent a turf war between the Wharfies and members of the Painters and Dockers. Poss is now working with lawyer Robert Bax to have his case re-opened. He believes his story to be a cautionary tale for young men. It is a chronicle of social change, including the sexual revolution of the sixties, the confrontations with “the demons” in the streets of Brisbane during the Joh era of Bible-bashing fundamentalism and police corruption. It’s a story about what really went on behind closed doors in institutions where vulnerable children were preyed upon, in gaols where men were expected to become beasts. It is a story of how the taint of a terrible crime affected a man’s whole life. “QUESTIONS OF OWNERSHIP” Writing someone else’s story can be an ethical minefield─especially regarding questions of ownership. Who owns the story, the subject or the author? The easy answer to this is the subject owns the story and the author the text, but on closer examination this may not necessarily be so. Then there are those other stakeholders who claim ownership of story: people who embrace a narrative because of its similarity to their own lives. Published stories about institutional abuse have resonated for adults who as children were placed into the care of churches or the state. Another kind of ownership is claimed by readers who accept a version of a story and dismiss any counter-story as being invalid. What I call the “Plath Phenomenon” is an example of this. I will examine these kinds of ownership of story with particular reference to the work of Janet Malcolm on biography and then will look at gaps and silences in “official” stories, those created in police stations and courtrooms.

Abstracts THE TAINT This is a memoir of Ray “Poss” Ide, a man who has carried the taint of a horrifying crime since he was seventeen years old─a crime he claims he did not commit. The crime was the rape of a fourteen-year-old girl. The Taint looks at the time leading up to his conviction for rape, including the years he spent in Westbrook Boys’ Reformatory and Boggo Road Gaol as a minor, and then his sentence served in NSW gaols with such inmates as Stephen Bradley, the man who kidnapped and murdered Graham Thorne, and the bizarre but rather likeable Dave Scanlan, known for his exploits as “the Kingsgrove Slasher”. In prison, Scanlan encouraged him to become an elite sportsman and released, Poss was recruited by Canterbury Eels football team; but just on the point of making a name for himself in Sydney, someone discovered that he had been gaoled for rape, and humiliated, he left the team. He moved back home to Queensland via Grafton, NSW (where he met and later married the Jacaranda Queen) and continued his sporting career, but never again in the Big League. He became the Manager of the Waterside Workers’ Club and helped prevent a turf war between the Wharfies and members of the Painters and Dockers. Poss is now working with lawyer Robert Bax to have his case re-opened. He believes his story to be a cautionary tale for young men. It is a chronicle of social change, including the sexual revolution of the sixties, the confrontations with “the demons” in the streets of Brisbane during the Joh era of Bible-bashing fundamentalism and police corruption. It’s a story about what really went on behind closed doors in institutions where vulnerable children were preyed upon, in gaols where men were expected to become beasts. It is a story of how the taint of a terrible crime affected a man’s whole life. “QUESTIONS OF OWNERSHIP” Writing someone else’s story can be an ethical minefield─especially regarding questions of ownership. Who owns the story, the subject or the author? The easy answer to this is the subject owns the story and the author the text, but on closer examination this may not necessarily be so. Then there are those other stakeholders who claim ownership of story: people who embrace a narrative because of its similarity to their own lives. Published stories about institutional abuse have resonated for adults who as children were placed into the care of churches or the state. Another kind of ownership is claimed by readers who accept a version of a story and dismiss any counter-story as being invalid. What I call the “Plath Phenomenon” is an example of this. I will examine these kinds of ownership of story with particular reference to the work of Janet Malcolm on biography and then will look at gaps and silences in “official” stories, those created in police stations and courtrooms.

Abstracts THE TAINT This is a memoir of Ray “Poss” Ide, a man who has carried the taint of a horrifying crime since he was seventeen years old─a crime he claims he did not commit. The crime was the rape of a fourteen-year-old girl. The Taint looks at the time leading up to his conviction for rape, including the years he spent in Westbrook Boys’ Reformatory and Boggo Road Gaol as a minor, and then his sentence served in NSW gaols with such inmates as Stephen Bradley, the man who kidnapped and murdered Graham Thorne, and the bizarre but rather likeable Dave Scanlan, known for his exploits as “the Kingsgrove Slasher”. In prison, Scanlan encouraged him to become an elite sportsman and released, Poss was recruited by Canterbury Eels football team; but just on the point of making a name for himself in Sydney, someone discovered that he had been gaoled for rape, and humiliated, he left the team. He moved back home to Queensland via Grafton, NSW (where he met and later married the Jacaranda Queen) and continued his sporting career, but never again in the Big League. He became the Manager of the Waterside Workers’ Club and helped prevent a turf war between the Wharfies and members of the Painters and Dockers. Poss is now working with lawyer Robert Bax to have his case re-opened. He believes his story to be a cautionary tale for young men. It is a chronicle of social change, including the sexual revolution of the sixties, the confrontations with “the demons” in the streets of Brisbane during the Joh era of Bible-bashing fundamentalism and police corruption. It’s a story about what really went on behind closed doors in institutions where vulnerable children were preyed upon, in gaols where men were expected to become beasts. It is a story of how the taint of a terrible crime affected a man’s whole life. “QUESTIONS OF OWNERSHIP” Writing someone else’s story can be an ethical minefield─especially regarding questions of ownership. Who owns the story, the subject or the author? The easy answer to this is the subject owns the story and the author the text, but on closer examination this may not necessarily be so. Then there are those other stakeholders who claim ownership of story: people who embrace a narrative because of its similarity to their own lives. Published stories about institutional abuse have resonated for adults who as children were placed into the care of churches or the state. Another kind of ownership is claimed by readers who accept a version of a story and dismiss any counter-story as being invalid. What I call the “Plath Phenomenon” is an example of this. I will examine these kinds of ownership of story with particular reference to the work of Janet Malcolm on biography and then will look at gaps and silences in “official” stories, those created in police stations and courtrooms.

No description available.

No description available.

本研究以「社會物質政治性」觀點主張Facebook的人際監控是由人／物共構而產生的政治性現象。Facebook所打造的物質展現，因無法避免地鑲嵌了「連結」意圖，以及由「人」集體構成的「分享」規範，在人與物的互動交引纏繞之下，而意外構成了人際監控。 本研究透過綜合式研究方法，包括田野觀察、半結構式深度訪談以及自我經驗書寫與分析，檢視Facebook使用者與Facebook之物質展現的互動關係如何構成監控與抵抗發現，人與物所產出的「網絡」及「個人脈絡」不但讓人們所設下的各種界線被無限擴張而構成了「無限擴張的網絡」、甚至因為「網絡」當中未曾消弭的各種權力關係，以及揭露人們所思所處所做的「個人脈絡」構成了「個人脈絡之曝露」，而成為了助長人際監控最重要的元素。 因此人們針對「網絡」的抵抗進行了「多重舞台隱藏設定」，以及針對「個人脈絡」進行了「展演式公開演出」抵抗。由於在強調互動與分享的Facebook當中，人與人之間形成的「監控」已不再扮演以往的霸權角色，而是形成了溢散的一種可被意識的力量之時，人們的「抵抗」亦脫離規避強權之目的性，並成為「抵抗者」為了保持自身的可視性以創造與維持社會關係，而策略性地透過Scott（1990）提出的「公開文本」進行「展演式公開演出」，以及透過「隱藏文本」進行「多重舞台隱藏設定」規避式抵抗。因此，人們在社群媒體的「抵抗」為一種挪用「公開／隱藏文本」不斷進行切換與游移的抵抗演出，進行部分的掩蓋、部分的揭露來達到人們預期目的，藉以尋求不那樣地被牽制的可能性。 透過「社會物質政治性」這樣的視野，本研究並非如以往具有科技決定色彩主張「物」牽制了人，也並未擁抱社會建構觀點，而是試圖提出由「人／物共構」的互動關係之下，因為意想不到的政治性例如物質的展現與特性、還有人們的互動實踐，皆可以扮演構成監控與抵抗的角色。 / Based on the perspective of “sociomaterialitics” this study argued that Facebook interpersonal surveillance was the political result of co-construction of human and material. Connectivity intention that hide beneath the material presentation of Facebook as well as the collective sharing normativity, entangled through the interactivities between human and material have resulted the unintentional construction of interpersonal surveillance. By using field observation, in-depth interview and analysis of self-experience, this study is able to explore the interactive relationship between human and material to find out how surveillance and resistance are co-constructed in Facebook. Network(ed) and personal context are found to have damage various boundaries of users which caused them to face “unlimited network expansion”, and because of the “underlying still-existence of power relations” in the network(ed), as well as “personal context” that caused “exposure of context”, are believed to have augmented surveillance in Facebook. People resist to network(ed) with “hidden setting of multi-stages”, and resist to exposure of personal context with “official performance”. However, as resistance was no longer the direct opposition to the oppression of dominant power in Facebook, hence “resistors” maintain their visibility and social relations strategically through the performance of “official transcript” and hiding themselves from surveillance through the “hidden transcript” in order to avoid unwanted results simultaneously (Scott, 1990). Therefore resistance in social media has transformed into “official/hidden transcripts” in which people switching their “official/hidden transcripts” constantly, continuously and strategically in order to partially performance and partially hiding themselves. As Facebook is a place that people voluntarily disclosed themselves, and hence interpersonal surveillance is seen as a conscious force in diffusion form, and people’s resistance is a self-reflexive strategic actions in liquidity form. People appropriated resistance to achieve intentional goals in order to explore possibilities of less containment derived from the co-construction of surveillance in social media. Through the perspective of “sociomaterialitics”, this study is able to escape from technological determinism and social constructionism, in order to embrace the idea of co-construction.