Charge Regulation during Amyloid Formation of α-Synuclein

[Image: see text] Electrostatic interactions play crucial roles in protein function. Measuring pK(a) value perturbations upon complex formation or self-assembly of e.g. amyloid fibrils gives valuable information about the effect of electrostatic interactions in those processes. Site-specific pK(a) value determination by solution NMR spectroscopy is challenged by the high molecular weight of amyloid fibrils. Here we report a pH increase during fibril formation of α-synuclein, observed using three complementary experimental methods: pH electrode measurements in water; colorimetric changes of a fluorescent indicator; and chemical shift changes for histidine residues using solution state NMR spectroscopy. A significant pH increase was detected during fibril formation in water, on average by 0.9 pH units from 5.6 to 6.5, showing that protons are taken up during fibril formation. The pH upshift was used to calculate the average change in the apparent pK(a)(ave) value of the acidic residues, which was found to increase by at least 1.1 unit due to fibril formation. Metropolis Monte Carlo simulations were performed on a comparable system that also showed a proton uptake due to fibril formation. Fibril formation moreover leads to a significant change in proton binding capacitance. Parallel studies of a mutant with five charge deletions in the C-terminal tail revealed a smaller pH increase due to fibril formation, and a smaller change (0.5 units on average) in the apparent pK(a)(ave) values of the acidic residues. We conclude that the proton uptake during the fibril formation is connected to the high density of acidic residues in the C-terminal tail of α-synuclein

WEFTA-Laborvergleichsuntersuchungen zur pH-Bestimmung in Fischerei-Erzeugnissen - Eine gemeinsame Aktion der Western European Fish Technologists' Association

12 samples (6 original samples and 6 diluted samples) were analysed by 14 WEFTA laboratories for their pH values in an inter-laboratory comparison exercise. As a result it can be stated that the majority of participating laboratories could determine the pH values very exactly. The pH values obtained are ranging only little around the calculated mean (less than 0.1 pH unit). It could also be demonstrated that the participating institutes could analyse both, pH values in fishery products and aqueous salt solutions. However, also in this exercise a number of outliers and deviating values have been detected. Therefore it is of utmost importance to calibrate the pH electrodes in regular intervals and to maintain them carefully. Intra-laboratory comparison measurements are recommended to detect weak points

Speech and language therapists’ perspectives of therapeutic alliance construction and maintenance in aphasia rehabilitation post stroke

Background: Therapeutic alliance refers to the interactional and relational processes operating during therapeutic interventions. It been shown to be a strong determinant of treatment efficacy in psychotherapy and evidence is emerging from a range of healthcare and medical disciplines to suggest that the construct of therapeutic alliance may in fact be a variable component of treatment outcome, engagement and satisfaction. Although this construct appears to be highly relevant to aphasia rehabilitation, no research to date has attempted to explore this phenomenon and thus consider its potential utility as a mechanism for change. Aims: This novel study aims to explore speech and language therapists’ perceptions and experiences of developing and maintaining therapeutic alliances in aphasia rehabilitation post stroke. Methods & Procedures: Twenty two, in-depth, semi-structured interviews were conducted with speech and language therapists working with people with aphasia post stroke. Qualitative data were analysed using inductive thematic analysis. Outcomes & Results: Analysis resulted in the emergence of three overarching themes: 1) laying the groundwork; 2) augmenting cohesion; and, 3) contextual shapers. Recognising personhood, developing shared expectations of therapy and establishing therapeutic ownership were central to laying the groundwork for therapeutic delivery. Augmenting cohesion was perceived to be dependent on the therapists’ responsiveness and ability to resolve both conflict and resistance, as part of an ongoing active process. These processes were further moulded by contextual shapers such as the patient’s family, relational continuity and organisational drivers. Conclusions & Implications: The findings suggest that therapists used multiple, complex relational strategies to establish and manage alliances with people with aphasia, which were reliant on a fluid interplay of verbal and non-verbal skills. The data highlight the need for further training to support therapists to forge purposive alliances. Training should develop: therapeutic reflexivity; inclusivity in goal setting, relational strategies and motivational enhancement techniques. The conceptualisation of therapeutic alliance, however, is only provisional. Further research is essential to elucidate the experiences and perceptions of alliance development for people with aphasia undergoing rehabilitation

Problemen med det personliga och det politiska : från kvinnors frigörelse till kvinnors mänskliga rättigheter

In this dissertation, I analyze understandings and employment of the idea that ‘the personal is political’ and how it appears in feminist politico-theoretical thought and activism in the period from the late 1960s until the middle of 1990s. My focus is primarily on the uses of personal stories in activism at the intersections of politics and legal discourse. The period in question is characterized by an evolving global feminist movement that gradually turned towards the framework of human rights. I explore two events that took place on either side of the human rights turn. These events are two international People’s Tribunals and their respective theoretical and historical contexts. The two tribunals were outspoken feminist initiatives, one held in Brussels in 1976 and the other in Vienna in 1993. They were organized by different actors at different historical moments who nevertheless identified themselves as being participants in a common international or global women’s movement. Their common denominator was both the choice of the form of a people’s tribunal and their aim of transcending national borders. Yet, their frameworks and language differ significantly. The first tribunal, Crimes against Women, held in Brussels in 1976, was planned as a radical feminist grassroots event, an upfront and critical response in opposition to the United Nations Conference on Women held in Mexico in 1975. In Brussels, feminist consciousness raising was fused with the method of a people’s tribunal to contribute to the creation of a transnational feminist political subject. Testimonies included personal stories of oppression and sexual violence, and they were meant to educate and motivate the women themselves in their struggle. There were no judges involved in the ‘trial’ procedures because the organizers and participants claimed that women had had enough of being judged by a patriarchal society. The event was for women only and no media were allowed to attend. Inspired by the tribunal in Brussels, the Vienna Tribunal on Women’s Human Rights, however, was planned in relation to the UN’s Conference on Human Rights in 1993, with the conceptual framework “Women’s Rights are Human Rights.” Testimonies were now directed outwardly, and strategically-selected judges commented and promised to offer support for the campaign to include gender-based violence in the human rights framework. My analytical focus is on three interrelated and overarching threads. Firstly, I identify ideas about politics found in the tribunal texts and the theoretical contexts that I place them in. Secondly, I trace the genealogy of violence against women as an international political issue. This converges with the history of transnational feminist activism, the rise of the human rights discourse and the search for common denominators. Thirdly, I look at the affective dimensions of the personal story as a political mobilizer. I argue that they change significantly according to historical, institutional and theoretical (ideological) context. Although the strategy of using personal testimonies might at first sight seem to be the greatest similarity that links the two events, the ‘method’ underwent some significant changes. I argue that the focus in Brussels was on creating a ‘counter-public’, to cultivate the participant’s own political emotions, notably righteous anger and to forge transnational feminist consciousness and solidarity, whereas, in Vienna, the framework had a more strategic character, as the individual stories were aimed at personalizing the political and motivating the empathy or compassion of an audience

Problemen med det personliga och det politiska : från kvinnors frigörelse till kvinnors mänskliga rättigheter

In this dissertation, I analyze understandings and employment of the idea that ‘the personal is political’ and how it appears in feminist politico-theoretical thought and activism in the period from the late 1960s until the middle of 1990s. My focus is primarily on the uses of personal stories in activism at the intersections of politics and legal discourse. The period in question is characterized by an evolving global feminist movement that gradually turned towards the framework of human rights. I explore two events that took place on either side of the human rights turn. These events are two international People’s Tribunals and their respective theoretical and historical contexts. The two tribunals were outspoken feminist initiatives, one held in Brussels in 1976 and the other in Vienna in 1993. They were organized by different actors at different historical moments who nevertheless identified themselves as being participants in a common international or global women’s movement. Their common denominator was both the choice of the form of a people’s tribunal and their aim of transcending national borders. Yet, their frameworks and language differ significantly. The first tribunal, Crimes against Women, held in Brussels in 1976, was planned as a radical feminist grassroots event, an upfront and critical response in opposition to the United Nations Conference on Women held in Mexico in 1975. In Brussels, feminist consciousness raising was fused with the method of a people’s tribunal to contribute to the creation of a transnational feminist political subject. Testimonies included personal stories of oppression and sexual violence, and they were meant to educate and motivate the women themselves in their struggle. There were no judges involved in the ‘trial’ procedures because the organizers and participants claimed that women had had enough of being judged by a patriarchal society. The event was for women only and no media were allowed to attend. Inspired by the tribunal in Brussels, the Vienna Tribunal on Women’s Human Rights, however, was planned in relation to the UN’s Conference on Human Rights in 1993, with the conceptual framework “Women’s Rights are Human Rights.” Testimonies were now directed outwardly, and strategically-selected judges commented and promised to offer support for the campaign to include gender-based violence in the human rights framework. My analytical focus is on three interrelated and overarching threads. Firstly, I identify ideas about politics found in the tribunal texts and the theoretical contexts that I place them in. Secondly, I trace the genealogy of violence against women as an international political issue. This converges with the history of transnational feminist activism, the rise of the human rights discourse and the search for common denominators. Thirdly, I look at the affective dimensions of the personal story as a political mobilizer. I argue that they change significantly according to historical, institutional and theoretical (ideological) context. Although the strategy of using personal testimonies might at first sight seem to be the greatest similarity that links the two events, the ‘method’ underwent some significant changes. I argue that the focus in Brussels was on creating a ‘counter-public’, to cultivate the participant’s own political emotions, notably righteous anger and to forge transnational feminist consciousness and solidarity, whereas, in Vienna, the framework had a more strategic character, as the individual stories were aimed at personalizing the political and motivating the empathy or compassion of an audience. 

Problemen med det personliga och det politiska : från kvinnors frigörelse till kvinnors mänskliga rättigheter

In this dissertation, I analyze understandings and employment of the idea that ‘the personal is political’ and how it appears in feminist politico-theoretical thought and activism in the period from the late 1960s until the middle of 1990s. My focus is primarily on the uses of personal stories in activism at the intersections of politics and legal discourse. The period in question is characterized by an evolving global feminist movement that gradually turned towards the framework of human rights. I explore two events that took place on either side of the human rights turn. These events are two international People’s Tribunals and their respective theoretical and historical contexts. The two tribunals were outspoken feminist initiatives, one held in Brussels in 1976 and the other in Vienna in 1993. They were organized by different actors at different historical moments who nevertheless identified themselves as being participants in a common international or global women’s movement. Their common denominator was both the choice of the form of a people’s tribunal and their aim of transcending national borders. Yet, their frameworks and language differ significantly. The first tribunal, Crimes against Women, held in Brussels in 1976, was planned as a radical feminist grassroots event, an upfront and critical response in opposition to the United Nations Conference on Women held in Mexico in 1975. In Brussels, feminist consciousness raising was fused with the method of a people’s tribunal to contribute to the creation of a transnational feminist political subject. Testimonies included personal stories of oppression and sexual violence, and they were meant to educate and motivate the women themselves in their struggle. There were no judges involved in the ‘trial’ procedures because the organizers and participants claimed that women had had enough of being judged by a patriarchal society. The event was for women only and no media were allowed to attend. Inspired by the tribunal in Brussels, the Vienna Tribunal on Women’s Human Rights, however, was planned in relation to the UN’s Conference on Human Rights in 1993, with the conceptual framework “Women’s Rights are Human Rights.” Testimonies were now directed outwardly, and strategically-selected judges commented and promised to offer support for the campaign to include gender-based violence in the human rights framework. My analytical focus is on three interrelated and overarching threads. Firstly, I identify ideas about politics found in the tribunal texts and the theoretical contexts that I place them in. Secondly, I trace the genealogy of violence against women as an international political issue. This converges with the history of transnational feminist activism, the rise of the human rights discourse and the search for common denominators. Thirdly, I look at the affective dimensions of the personal story as a political mobilizer. I argue that they change significantly according to historical, institutional and theoretical (ideological) context. Although the strategy of using personal testimonies might at first sight seem to be the greatest similarity that links the two events, the ‘method’ underwent some significant changes. I argue that the focus in Brussels was on creating a ‘counter-public’, to cultivate the participant’s own political emotions, notably righteous anger and to forge transnational feminist consciousness and solidarity, whereas, in Vienna, the framework had a more strategic character, as the individual stories were aimed at personalizing the political and motivating the empathy or compassion of an audience. 

Extracting ECA rules from UML

Active technology in database management systems (DBMS) enables the movement of behaviour dependent on the system’s state, from the application software to a rule base in the DBMS. With active technology in database systems, the problem of how to design active behaviour has become an important issue. Modelling processes do not foresee support for design of active rules which can lead to conflicts between the event-condition-action (ECA) rules representing the active behaviour and the application systems, using the active DBMS. The unified modelling language (UML) is a widely used notation language and is the main subject in this project. Its features will be investigated to acknowledge to what extend UML modelling diagrams provide information that can be used to formulate ECA rules. To achieve this, two methods where developed. One of the methods was applied on use-case UML modelling diagrams. The use-case models were developed by means of reflecting a real-life organisation. The results from applying the method on the use-case models were that there are features in UML that can be expressed with ECA rules. Active technology in database management systems (DBMS) enables the movement of behaviour dependent on the system’s state, from the application software to a rule base in the DBMS. With active technology in database systems, the problem of how to design active behaviour has become an important issue. Modelling processes do not foresee support for design of active rules which can lead to conflicts between the event-condition-action (ECA) rules representing the active behaviour and the application systems, using the active DBMS. The unified modelling language (UML) is a widely used notation language and is the main subject in this project. Its features will be investigated to acknowledge to what extend UML modelling diagrams provide information that can be used to formulate ECA rules. To achieve this, two methods where developed. One of the methods was applied on use-case UML modelling diagrams. The use-case models were developed by means of reflecting a real-life organisation. The results from applying the method on the use-case models were that there are features in UML that can be expressed with ECA rules

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Pallidal stimulation-induced psychosis and suicidality in Parkinson’s disease

Neuropsychiatric adverse events have been previously reported following deep brain stimulation (DBS) for Parkinson’s disease (PD). Most cases described have involved DBS of the subthalamic nucleus (STN). We report a unique case of acute-onset and reversible psychosis, suicidality, and depressive symptoms following DBS of the globus pallidus internus (GPi) and review the relevant literature