Thesis (Ph. D.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

<p>Varumärkesdegeneration innebär att ett varumärke förlorar sin särskiljningsförmåga och övergår till att bli en produktbeteckning, en generisk term. När särskiljningsförmågan försvinner mister varumärket sin huvudsakliga funktion - att särskilja innehavarens varor från andra näringsidkares varor av samma slag. En ensamrätt till en produktbeteckning medför vidare att övriga näringsidkare får problem att beskriva sina produkter i marknadsföring eller vid försäljning. Ett varumärke som degenererat är således odugligt som varumärke och kan därför inte längre vara föremål för någon varumärkesrättslig ensamrätt. En näringsidkare som lider förfång av ett varumärke som förvandlats till en generisk beteckning kan därför kräva att allmän domstol häver varumärkesregistreringen, varpå ensamrätten till varumärket upphör att gälla. Varumärket blir då fritt tillgängligt för alla näringsidkare att använda.</p><p>Att förlora ett värdefullt varumärke kan få förödande konsekvenser för en varumärkesinnehavare. Det är därför viktigt att skydda sitt varumärke från att degenerera. Har en varumärkesinnehavare kunskap om varumärkesdegenerationens orsaker och konsekvenser är möjligheterna att skydda varumärket från degeneration mycket goda. Varumärkesdegeneration kan uppstå av många orsaker. Ett varumärke med låg särskiljningsförmåga, avsaknad av en generisk beteckning, samt inkorrekt användning av dessa är exempel på riskfaktorer. Det är därför viktigt att varumärket har ett namn med hög särskiljningsförmåga, att det introduceras med en funktionell generisk beteckning och att båda dessa används korrekt. För att förstå vad detta innebär i praktiken krävs en semantisk undersökning av varumärkets funktion, dess särskiljningsförmåga och vad som egentligen sker när ett varumärke degenererar. Ju bättre en varumärkesinnehavare förstår ett varumärkes funktion, desto bättre kan han eller hon skydda det.</p><p>Varumärkesdegeneration är juridiskt sett ett relativt ovanligt fenomen. Även om det i Sverige finns flera exempel på varumärken som idag används generiskt är det få varumärkesregistreringar som, enligt nuvarande varumärkesrätt, de facto hävts. Detta kan bero på att den bevisning som krävs för att ett varumärke ska bedömas ha degenererat i allmän domstol är mycket sträng. Varumärkesdegenerationen måste vara fullbordad. Således måste en överväldigande majoritet av omsättningskretsen uppfatta varumärket som generiskt. Vilka som skall ingå i den relevanta omsättningskretsen är en omdebatterad fråga. Enligt förarbetena till VmL ska tidigare distributionsled, det vill säga grosshandeln, varuhusens och detaljhandels inköpsavdelningar etc., väga tyngre än senare. Hur varumärket uppfattas av butikspersonal eller av konsumenterna är av mindre betydelse för bedömningen. Varumärken har dock inte samma funktion idag som det hade när dessa förarbeten författades. Globalisering och Internethandel har gjort att konsumenter idag har betydligt större makt än de hade i slutet av 50-talet. Vi anser att avgörande omständigheter skall återspegla faktiska förhållanden. Det sätt på vilket ett varumärke används idag, för att varumärkesrätten i framtiden ska komma att bli så rättvis som möjligt, bör därför undersökas ytterligare.</p> / <p>The principal purpose of a trade mark is to individualize products from a certain business. This quality is called distinctiveness. When the distinctiveness disappears the trade mark is said to have degenerated. The trade mark has then developed into a common noun, a generic term, and can no longer function as an individualizing designation. A degenerated trade mark might confuse the consumers and cause unfair competition. A trade mark proprietor, who suffers from a trade mark turning into a common noun, can therefore claim that a public court has the trade mark title cancelled. The degenerated trade mark then becomes available to all.</p><p>For a trade mark proprietor, losing a trade mark can be devastating. It is therefore important to avoid degeneration. However, if the trade mark proprietor understands the causes and consequences of degeneration, avoiding it is relatively easy. Case studies show that degeneration is caused mainly by misuse of the trade mark and the generic term. Thus, coining and using both a trade mark and a practicable generic term are two of the most important anti-degenerative measures. The trade mark proprietor must understand the effects of use on the distinctiveness of the trade mark and what happens linguistically when a trade mark degenerates. The better the trade mark proprietor understands the function of the trade mark, the better he can protect it.</p><p>Degeneration is an unusual phenomenon. Even if there are several trade marks that are used generically in our language today, there are few cases in Swedish law where a trade mark title has been actually cancelled. This can be due to the fact that the evidence which must be adduced in cases of degeneration must be very strong. The degeneration has to be completed, thus, an overwhelming majority in the relevant circles must use the trade mark generically. And which people that shall be included in the relevant circles is somewhat unclear. According to the preparations of the Swedish trade mark law the previous links in the distribution chain, e.g. suppliers, purchasers etc., shall be of higher relevance than the later. How the trade mark is used by store personal or consumers are not as important in the judgment. However, the trade marks of today have not the same function as when the preparations where written. Globalization and the Internet commerce have given the consumers of today considerably more power than in the late 1950’s. And we believe that conclusive circumstances shall reflect actual conditions. For the trade mark law to become as fair as possible, the way that a trade mark is used today ought to be examined further.</p>

Retinal degeneration is characterized by the irreversible loss of photoreceptors. A key research question is the identification and characterization of photoreceptor protective factors that prevent or delay vision loss. The Wnt pathway is a critical cellular communication pathway involved in development and diseases of the central nervous system (CNS). Recently, we discovered that multiple components of the Wnt pathway were differentially expressed in the rd1 mouse model of retinal degeneration. One of the most highly upregulated genes was Dickkopf3 (Dkk3), a secreted Wnt pathway protein of unknown function. Additionally, we demonstrated that Wnt signaling is neuroprotective in primary retinal culture (Yi et al., 2007). These data led to the hypothesis that Dkk3 is a regulator of Wnt-mediated neuroprotection during retinal degeneration. The role of Dkk3 in the retina and its activity in the Wnt pathway was identified in this dissertation project using a series of biochemical, molecular and cell biology methodologies. First, Dkk3 was shown to be expressed and secreted from Muller glia in mouse retinal tissue and primary Muller glia culture. I then demonstrated that Muller glia are a Wnt-responsive cell type and that Dkk3 potentiates Wnt3a-mediated signaling. Interestingly, the latter effect was not observed in other cell types in the retina such as retinal ganglion cells and retinal pigmented epithelial cells. Thus, Dkk3 may act on Muller glia to positively modulate Wnt signaling during retinal degeneration, which could potentially amplify the neuroprotective activity of the Wnt pathway. Next, the role of Dkk3 in cellular viability was explored. HEK293 cells stably expressing Dkk3 were shown to be significantly protected from staurosporine-induced apoptosis compared with vector control. This result suggests that Dkk3 may mediate a direct pro-survival effect onto photoreceptors during retinal degeneration. Protein interaction experiments demonstrated that Dkk3 formed a complex with the single pass transmembrane proteins Krm1 and Krm2 in the membrane, potentially in the endoplasmic reticulum (ER). Furthermore, Wnt signaling luciferase reporter assays demonstrated that Krm2, but not Krm1, abolished Dkk3-mediated Wnt3a potentiation. These data suggest that Dkk3 modulates Wnt signaling by antagonizing Dkk1-Krm dependent Wnt inhibition. Further studies will determine whether this activity is sufficient for the potentiation of Wnt signaling by Dkk3. Lastly, co-immunoprecipitation followed by mass spectrometry analysis was used to identify a novel interacting protein of Dkk3. Dkk3 was shown to interact with glucose response protein 78 (GRP78), an ER-resident chaperone. This suggested that Dkk3 protein is part of the unfolded protein response through GRP78 in the ER. In conclusion, these studies identified two novel functions of Dkk3 in regulating Wnt signaling pathway and cellular viability and suggest a physiological role for Dkk3 and Wnt signaling during retinal degeneration. Future studies will explore the significance of Dkk3-Krm and Dkk3-GRP78 interactions in the retina. Further, elucidation of the regulation of Dkk3 and other Wnt ligands in the ER and the consequence of ER stress on the biological activity of Wnt signaling will provide a better understanding of the role of the Wnt pathway during retinal degeneration.

Varumärkesdegeneration innebär att ett varumärke förlorar sin särskiljningsförmåga och övergår till att bli en produktbeteckning, en generisk term. När särskiljningsförmågan försvinner mister varumärket sin huvudsakliga funktion - att särskilja innehavarens varor från andra näringsidkares varor av samma slag. En ensamrätt till en produktbeteckning medför vidare att övriga näringsidkare får problem att beskriva sina produkter i marknadsföring eller vid försäljning. Ett varumärke som degenererat är således odugligt som varumärke och kan därför inte längre vara föremål för någon varumärkesrättslig ensamrätt. En näringsidkare som lider förfång av ett varumärke som förvandlats till en generisk beteckning kan därför kräva att allmän domstol häver varumärkesregistreringen, varpå ensamrätten till varumärket upphör att gälla. Varumärket blir då fritt tillgängligt för alla näringsidkare att använda. Att förlora ett värdefullt varumärke kan få förödande konsekvenser för en varumärkesinnehavare. Det är därför viktigt att skydda sitt varumärke från att degenerera. Har en varumärkesinnehavare kunskap om varumärkesdegenerationens orsaker och konsekvenser är möjligheterna att skydda varumärket från degeneration mycket goda. Varumärkesdegeneration kan uppstå av många orsaker. Ett varumärke med låg särskiljningsförmåga, avsaknad av en generisk beteckning, samt inkorrekt användning av dessa är exempel på riskfaktorer. Det är därför viktigt att varumärket har ett namn med hög särskiljningsförmåga, att det introduceras med en funktionell generisk beteckning och att båda dessa används korrekt. För att förstå vad detta innebär i praktiken krävs en semantisk undersökning av varumärkets funktion, dess särskiljningsförmåga och vad som egentligen sker när ett varumärke degenererar. Ju bättre en varumärkesinnehavare förstår ett varumärkes funktion, desto bättre kan han eller hon skydda det. Varumärkesdegeneration är juridiskt sett ett relativt ovanligt fenomen. Även om det i Sverige finns flera exempel på varumärken som idag används generiskt är det få varumärkesregistreringar som, enligt nuvarande varumärkesrätt, de facto hävts. Detta kan bero på att den bevisning som krävs för att ett varumärke ska bedömas ha degenererat i allmän domstol är mycket sträng. Varumärkesdegenerationen måste vara fullbordad. Således måste en överväldigande majoritet av omsättningskretsen uppfatta varumärket som generiskt. Vilka som skall ingå i den relevanta omsättningskretsen är en omdebatterad fråga. Enligt förarbetena till VmL ska tidigare distributionsled, det vill säga grosshandeln, varuhusens och detaljhandels inköpsavdelningar etc., väga tyngre än senare. Hur varumärket uppfattas av butikspersonal eller av konsumenterna är av mindre betydelse för bedömningen. Varumärken har dock inte samma funktion idag som det hade när dessa förarbeten författades. Globalisering och Internethandel har gjort att konsumenter idag har betydligt större makt än de hade i slutet av 50-talet. Vi anser att avgörande omständigheter skall återspegla faktiska förhållanden. Det sätt på vilket ett varumärke används idag, för att varumärkesrätten i framtiden ska komma att bli så rättvis som möjligt, bör därför undersökas ytterligare. / The principal purpose of a trade mark is to individualize products from a certain business. This quality is called distinctiveness. When the distinctiveness disappears the trade mark is said to have degenerated. The trade mark has then developed into a common noun, a generic term, and can no longer function as an individualizing designation. A degenerated trade mark might confuse the consumers and cause unfair competition. A trade mark proprietor, who suffers from a trade mark turning into a common noun, can therefore claim that a public court has the trade mark title cancelled. The degenerated trade mark then becomes available to all. For a trade mark proprietor, losing a trade mark can be devastating. It is therefore important to avoid degeneration. However, if the trade mark proprietor understands the causes and consequences of degeneration, avoiding it is relatively easy. Case studies show that degeneration is caused mainly by misuse of the trade mark and the generic term. Thus, coining and using both a trade mark and a practicable generic term are two of the most important anti-degenerative measures. The trade mark proprietor must understand the effects of use on the distinctiveness of the trade mark and what happens linguistically when a trade mark degenerates. The better the trade mark proprietor understands the function of the trade mark, the better he can protect it. Degeneration is an unusual phenomenon. Even if there are several trade marks that are used generically in our language today, there are few cases in Swedish law where a trade mark title has been actually cancelled. This can be due to the fact that the evidence which must be adduced in cases of degeneration must be very strong. The degeneration has to be completed, thus, an overwhelming majority in the relevant circles must use the trade mark generically. And which people that shall be included in the relevant circles is somewhat unclear. According to the preparations of the Swedish trade mark law the previous links in the distribution chain, e.g. suppliers, purchasers etc., shall be of higher relevance than the later. How the trade mark is used by store personal or consumers are not as important in the judgment. However, the trade marks of today have not the same function as when the preparations where written. Globalization and the Internet commerce have given the consumers of today considerably more power than in the late 1950’s. And we believe that conclusive circumstances shall reflect actual conditions. For the trade mark law to become as fair as possible, the way that a trade mark is used today ought to be examined further.

Retinitis Pigmentosa (RP) refers to a group of inherited retinal dystrophies resulting from progressive photoreceptor degeneration and accumulation of intra-retinal pigment-like deposits. X-linked forms of RP are frequently caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The RPGR transcript undergoes complex alternative splicing to express both constitutive (RPGR^ex1-19) and RPGR^ORF15 variants. Although RPGR is thought to play a role in ciliary function, little is known about the physiological significance of expressing two distinct groups of variants. This study compares Rpgr^ex1-19 and Rpgr^ORF15 expression in developing photoreceptors using immunoblot analysis and immunohistochemistry, assesses ciliary affinity in adult photoreceptors by protein fractionation, examines Rpgr function in transgenic mouse models and identifies a novel Rpgr^ORF15 binding partner using a yeast two-hybrid screen. Our data reveal that Rpgr expression undergoes dynamic temporal regulation during retinal development and indicates variability in ciliary localization of Rpgr variants in adult photoreceptors. Utilization of distinct Rpgr variants during stages of photoreceptor development suggests independent roles. Further examination of Rpgr function using transgenic mouse models over-expressing either the Rpgr^ex1-19 or Rpgr^ORF15 variant reveals that despite normal ciliary localization, an excess of RPGR^ex1-19 results in atypical accumulation of Rpgr in photoreceptor outer segments, abnormal photoreceptor morphology and severe retinal degeneration. The data indicate that the constitutive variant cannot substitute for Rpgr function in photoreceptors and suggest that proper maintenance of the Rpgr isoform ratio is critical to photoreceptor viability. Using mouse retinal cDNA in a yeast two-hybrid screen with the C-terminus of the Rpgr^ORF15 variant, we identified a novel variant of whirlin as an interacting partner. Mutations in whirlin result in Usher syndrome, a disorder characterized by hearing loss and RP. RT-PCR and immunoblot analysis were used to confirm the presence of selected candidate partners in the retina and interaction was confirmed by pull-down assays and co-immunoprecipitation from retinal homogenate. Immunohistochemistry showed co-localization of RPGR and whirlin within photoreceptors and identified isoform specific localization of whirlin. These findings indicate that whirlin binds Rpgr^ORF15 and that this novel isoform may be required for photoreceptor function, thus providing a potential mechanism for the RP phenotype observed in Usher syndrome.

Age related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. At present, there are an estimated one million people in Canada with some form of AMD and this number is expected to double to two million by 2031. These estimates are sobering, and it is predicted that costs for treatment and care of individuals who suffer vision loss from AMD will have significant impact on the social and public health systems in Canada in the next two decades. There are treatments to slow the progression of vision loss, but unfortunately, there are currently no cures available for AMD. In order to develop effective second generation therapies and cures, further insights into how and why AMD develops are greatly needed. Recent studies have provided novel insights into the role of inflammation in the pathogenesis of AMD. Inflammation, or swelling of the retinal tissues, causes harmful processes that promote macular degeneration. The proposed studies will focus on the triggers of inflammation in the retina. It is hypothesized that macular degeneration may be slowed or stopped by eliminating the molecules that cause inflammation in the retina. This study will focus on amyloid beta (Aβ), a toxic molecule that has been implicated in retinal inflammation, and the role that it may play in gene expression of the retinal pigment epithelial cell. Amyloid beta is a well studied peptide in another age related disorder, Alzheimer’s disease. It is the major extracellular deposit in Alzheimer’s disease plaques, and has recently been discovered as a component of drusen, the hallmark extracellular deposits in the retina of patients with the ‘dry’ form of AMD. These studies will allow the development of new treatment regimens that target retinal inflammation and thus minimize the processes that ‘trigger’ the onset of macular degeneration.

Ongoing efforts to quantify changes in quality of life attributable to low vision rehabilitation have focused on the utility of a single test instrument to measure this multidimensional concept. It is hypothesized that quality of life is best assessed using multiple instruments to capture some of its component facets, including functional status and psychosocial impact. Low vision devices have a predictably spontaneous impact on functional vision status, but associated psychosocial impact occurs with different magnitudes and over more protracted time intervals. The National Eye Institute Visual Function Questionnaire (NEI VFQ-25) measures the functional status of individuals in key vision areas that are associated with quality of life. The Psychosocial Impact of Assistive Devices Scale (PIADS) is an instrument that measures the psychosocial impact of assistive device intervention in three quality of life domains: competence, adaptability, and self-esteem. 68 participants were obtained from an ongoing parent study. These participants were recruited through the Low Vision Clinic at the University of Waterloo. They had a primary diagnosis of age-related macular degeneration (ARMD) and were obtaining a CCTV system for the first time. Assessments from the parent study used in this thesis included follow-up from 2 weeks, 1 month, 3 months, and 6 months post-adoption of the CCTV. The two tests administered were to measure functional vision status (NEI VFQ-25) and perceived psychosocial impact (PIADS), according the framework outlined by the Consortium for Assistive Technology Outcomes Research (CATOR). Multivariate repeated-measures ANVOA results confirmed that CCTV systems have an immediate and robust effect on the daily visual functioning of their users, and that this effect is stable over long periods of device use. The psychosocial impact of CCTV device use peaks in the shorter term and then seems to wane in the longer term for reasons that are not yet understood. The NEI VFQ-25 and the PIADS appear to have differential sensitivity to important influences on low vision rehabilitation outcomes. This project has demonstrated the value of longitudinal outcomes research in low vision rehabilitation. After obtaining a CCTV, visual function status remains static while psychosocial impact is dynamic during 6-months of follow-up.

Ongoing efforts to quantify changes in quality of life attributable to low vision rehabilitation have focused on the utility of a single test instrument to measure this multidimensional concept. It is hypothesized that quality of life is best assessed using multiple instruments to capture some of its component facets, including functional status and psychosocial impact. Low vision devices have a predictably spontaneous impact on functional vision status, but associated psychosocial impact occurs with different magnitudes and over more protracted time intervals. The National Eye Institute Visual Function Questionnaire (NEI VFQ-25) measures the functional status of individuals in key vision areas that are associated with quality of life. The Psychosocial Impact of Assistive Devices Scale (PIADS) is an instrument that measures the psychosocial impact of assistive device intervention in three quality of life domains: competence, adaptability, and self-esteem. 68 participants were obtained from an ongoing parent study. These participants were recruited through the Low Vision Clinic at the University of Waterloo. They had a primary diagnosis of age-related macular degeneration (ARMD) and were obtaining a CCTV system for the first time. Assessments from the parent study used in this thesis included follow-up from 2 weeks, 1 month, 3 months, and 6 months post-adoption of the CCTV. The two tests administered were to measure functional vision status (NEI VFQ-25) and perceived psychosocial impact (PIADS), according the framework outlined by the Consortium for Assistive Technology Outcomes Research (CATOR). Multivariate repeated-measures ANVOA results confirmed that CCTV systems have an immediate and robust effect on the daily visual functioning of their users, and that this effect is stable over long periods of device use. The psychosocial impact of CCTV device use peaks in the shorter term and then seems to wane in the longer term for reasons that are not yet understood. The NEI VFQ-25 and the PIADS appear to have differential sensitivity to important influences on low vision rehabilitation outcomes. This project has demonstrated the value of longitudinal outcomes research in low vision rehabilitation. After obtaining a CCTV, visual function status remains static while psychosocial impact is dynamic during 6-months of follow-up.

This study evaluated whether cortical reorganization occurs in response to macular degeneration (MD), a progressive disorder of the retina that results in central vision loss. Past research has observed the ability of V1 to adapt to retinal damage, demonstrating that deafferented cortex is activated by the stimulation of intact retinal areas. It is still unclear, however, if and to what degree cortical reorganization is associated with specific forms of macular degeneration. This study evaluated the retinal health of MD participants (both age-related and juvenile) as well age-matched controls with computerized microperimetry. Contrast-reversing stimuli were then presented to different parts of the visual field while participants were scanned with functional magnetic resonance imaging (fMRI). For MD participants, stimulation of peripheral retinal areas elicited activation in deafferented cortex. This activation occurred for retinal areas adapted for eccentric viewing (preferred retinal locations), but not in preserved retina at the same eccentricity. These findings add to the scientific knowledge of plasticity in sensory systems by supporting an experience driven understanding of cortical reorganization. They could also have a meaningful impact on how macular degeneration is treated by informing the design of therapeutic training regimes.

The main contents of this thesis are improving a UWB LNA, and analyze the input-matching, the noise, and the gain. First we increase the width of the input transistor, and remove source-degeneration inductor. Those ways can increase the gain and reduce the noise of the circuit. In the input matching, we use a shunt capacitor, a series inductor, and the impedance of the transistor itself to achieve high frequency matching. The lower frequency matching is achieved by negative feedback resistor. The UWB LNA dissipates 10.14 mW power and achieves input return loss (S11) below -11.5 dB, output return loss (S22) below -11.9 dB, forward gain (S21) of 14.4¡Ó0.4 dB, reverse isolation (S12) below -26.7 dB, and noise figure (NF) of 2.6~3.5 dB over the 3.1~10.6 GHz band of interest. 1-dB compression point (P1dB) of -16.8 dBm and input third-order inter-modulation point (IIP3) of -8.1 dBm are achieved at 6.85 GHz.