Humanization, Radiolabeling and Biodistribution Studies of an IgG(1)-Type Antibody Targeting Uncomplexed PSA for Theranostic Applications

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A"-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications

Parallelizing the Edge application for GPU-based systems using the SkePU skeleton programming library

SkePU is an auto-tunable multi-backend skeleton programming library for multi-GPU systems. SkePU is implemented as a C++ template library and has been developed at Linköping University. In this thesis the CFD flow solver Edge has been ported to SkePU. This combines the paradigm of skeleton programming with the utilization of the unstructured grid structure used by Edge. In order to do this certain extensions have been made to the SkePU library. The performance of the ported implementation has been evaluated to identify if a performance gain can be achieved by parallelizing this type of application with the help of SkePU. A moderate speedup of the application has been achieved given the size of the ported section of the Edge application. Another important outcome of the project is the provided feedback for further development of the SkePU framework

Parallelizing the Edge application for GPU-based systems using the SkePU skeleton programming library

SkePU is an auto-tunable multi-backend skeleton programming library for multi-GPU systems. SkePU is implemented as a C++ template library and has been developed at Linköping University. In this thesis the CFD flow solver Edge has been ported to SkePU. This combines the paradigm of skeleton programming with the utilization of the unstructured grid structure used by Edge. In order to do this certain extensions have been made to the SkePU library. The performance of the ported implementation has been evaluated to identify if a performance gain can be achieved by parallelizing this type of application with the help of SkePU. A moderate speedup of the application has been achieved given the size of the ported section of the Edge application. Another important outcome of the project is the provided feedback for further development of the SkePU framework

Parallelizing the Edge application for GPU-based systems using the SkePU skeleton programming library

SkePU is an auto-tunable multi-backend skeleton programming library for multi-GPU systems. SkePU is implemented as a C++ template library and has been developed at Linköping University. In this thesis the CFD flow solver Edge has been ported to SkePU. This combines the paradigm of skeleton programming with the utilization of the unstructured grid structure used by Edge. In order to do this certain extensions have been made to the SkePU library. The performance of the ported implementation has been evaluated to identify if a performance gain can be achieved by parallelizing this type of application with the help of SkePU. A moderate speedup of the application has been achieved given the size of the ported section of the Edge application. Another important outcome of the project is the provided feedback for further development of the SkePU framework

Idrottsspecialisering på schemat?

Kommande examensarbete berör ungdomar i grundskolans senare år och som valt en tidig idrottsspecialisering. Syftet med examensarbetet har varit att ta reda på huruvida konsekvenserna av en tidig idrottsspecialisering speglar av sig i skolämnet idrott och hälsa. Detta ställs i relation till tidigare forskning inom området samt kursplaner och styrdokument från skolvärlden. Frågeställningarna som ligger till grund för examensarbetet lyder: Vad är elevernas uppfattningar gällande konsekvenser av tidig idrottsspecialisering? Hur visar sig konsekvenserna mellan tidig idrottsspecialisering och skolämnet Idrott och hälsa? Varför specialiserar sig ungdomar tidigt inom idrotten? Bakgrunden beskriver grundskolans kursplan inom idrott och hälsa samt idrottens policy dokument vidare berör bakgrunden även tidigare forskning som gjorts inom närliggande område. Metoden som använts för att söka svar på frågeställningarna är kvalitativa intervjuer. Informanterna har bestått av elever från grundskolans senare år med en tidig idrottsspecialisering, eleverna har valts ut av deras befintliga lärare. Den teorietiska utgångspunkten för arbetet är hämtat från Bourdieus sociologiska teori beträffande habitus, sociala fält, praktiker och kapital

Humanization, radiolabeling and biodistribution studies of an igg1-type antibody targeting uncomplexed psa for theranostic applications

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications

Mapping of apparent susceptibility yields promising diagnostic separation of progressive supranuclear palsy from other causes of parkinsonism

There is a need for methods that distinguish Parkinson’s disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), which have similar characteristics in the early stages of the disease. In this prospective study, we evaluate mapping of apparent susceptibility based on susceptibility weighted imaging (SWI) for differential diagnosis. We included 134 patients with PD, 11 with PSP, 10 with MSA and 44 healthy controls. SWI data were processed into maps of apparent susceptibility. In PSP, apparent susceptibility was increased in the red nucleus compared to all other groups, and in globus pallidus, putamen, substantia nigra and the dentate nucleus compared to PD and controls. In MSA, putaminal susceptibility was increased compared to PD and controls. Including all studied regions and using discriminant analysis between PSP and PD, 100% sensitivity and 97% specificity was achieved, and 91% sensitivity and 90% specificity in separating PSP from MSA. Correlations between putaminal susceptibility and disease severity in PD could warrant further research into using susceptibility mapping for monitoring disease progression and in clinical trials. Our study indicates that susceptibility in deep nuclei could play a role in the diagnosis of atypical parkinsonism, especially in PSP