Diplomats or Defendants? Defining the Future of Head-of-State Immunity

Fluorescence nanoscopy provides means to discernthe finer details of protein localization and interaction in cells by offeringan order of magnitude higher resolution than conventional optical imagingtechniques. However, these super resolution techniques put higher demands onthe optical system as well as on the fluorescent probes, making multicolorfluorescence nanoscopy a challenging task. Here we present a new and simpleprocedure which exploits the photostability and excitation spectra of dyes toincrease the number of simultaneous recordable targets in STED nanoscopy. Weuse this procedure to demonstrate four color STED imaging of platelets with ≤40 nm resolution and low crosstalk. Platelets can selectively store, sequesterand release a multitude of different proteins, and in a manner specific fordifferent physiological and disease states. By applying multicolor nanoscopy tostudy platelets, we can achieve spatial mapping of the protein organizationwith a high resolution, for multiple proteins at the same time and in the samecell. This provides a means to identify specific platelet activation states fordiagnostic purposes and to understand the underlying protein storage andrelease mechanisms. We studied the organization of the pro- and anti-angiogenicproteins VEGF and PF-4 together with fibrinogen and filamentous actin, andfound distinct features in their respective protein localization. Further,colocalization analysis revealed only minor overlap between the proteins VEGFand PF-4 indicating that they have separate storage and release mechanisms,corresponding well with their opposite rules as pro- and anti-angiogenicproteins, respectively.Updated from "Submitted" to "Published". QC 20140630</p

Niveles de presión arterial y cambios longitudinales en relación con factores de la red social: ¿Mejor juntos o por separado?

The aim of this study was to examine the relationship between social network variables andlevels of and longitudinal changes in blood pressure in a middle-aged/older sample. Theparticipants (50-75 years at baseline; n=1097) responded to questions concerning socialrelationships at baseline and their blood pressure (diastolic, systolic) was measured. Bloodpressure levels were reassessed 5, 10, and 15 years later. Latent growth models with responses toquestions concerning social relationships as predictors and basic demographic factors (age, sex) ascovariates, unexpectedly indicated that a more limited social network (no close friend, few visits,little contact with friends in other ways, not living with someone, and a composite index based onall questions) was associated with significantly lower diastolic blood pressure levels. For systolicblood pressure a similar result was observed for one of the variables (lack of a close friend). Ingeneral, these effects diminished over time, as indexed by the positive relationship between severalof the social variables and slope. The results were little affected by inclusion of additionalcovariates (e.g. measures of psychological distress, smoking/alcohol habits, and BMI) suggestingthat the origins of this unexpected pattern of findings must probably be sought for in other subjectrelatedfactors, such as, for example, increased help seeking. Future studies should considerqualitative aspects (e.g. feelings of loneliness, quality of social relationships) in addition tostructural aspects to provide a better understanding of these associations.El objetivo de este estudio fue examinar la relación entre las variables de la red social y losniveles de cambios longitudinales en la presión arterial en la muestra que consta de la gente demediana y tercera edad. Los participantes (50-75 años; n=1097) respondieron a las preguntas quetrataban el tema de relaciones sociales y se midió su presión arterial (diastólica, sistólica). Sevolvió a valorar los niveles de presión arterial 5, 10 y 15 años después. Modelos de crecimientolatente con respuestas a las preguntas que trataban el tema de relaciones sociales (o un índice)como predictores y factores demográficos básicos (edad, sexo) como covariables,inesperadamente, indicaron que la red social más limitada (sin amigos íntimos, con pocas visitas eíndice compuesto) se relacionaba con el nivel de presión arterial diastólica significativamente másbaja. Para la presión arterial sistólica se confirmó el resultado similar para una de las variables(falta de amigos cercanos). En general, estos efectos disminuyeron con el tiempo, según estáindexado por la relación positiva entre distintas variables sociales y la pendiente. La inclusión decovariables adicionales (p. ej. medición de trastornos psicológicos, hábitos de fumar y beberalcohol e IMC) afectaron un poco a los resultados, sugiriendo que los orígenes de este patrón deresultados inesperado probablemente los hay que buscar en los factores relacionados con el sujetoy no aquellos relacionados con el estilo de vida, como p. ej. aumento de la búsqueda de ayuda. Losfuturos estudios deberían considerar aspectos cualitativos (p. ej. sentimiento de soledad, calidad derelaciones sociales), además de los aspectos estructurales, para proporcionar un entendimientomejor de estas asociaciones

Super resolution optical imaging – image analysis, multicolor development and biological applications

This thesis focuses on super resolution STED optical imaging. STED provides a wealth of new informational content to the acquired images by using stimulated emission to surpass the diffraction limit in optical fluorescence microscopy. To further increase the informational content, a new method to perform multicolor STED imaging by exploiting differences in the photostability and excitation spectra of dyes is presented. In order to extract information from the images, computational algorithms which handle the new type of high resolution informational content are developed. We propose that multicolor super resolution imaging in combination with image analysis can reduce the amount of clinical samples required to perform accurate cancer diagnosis. To date, such diagnosis is based mainly on significant amounts of tissue samples extracted from the suspected tumor site. The sample extraction often requires anesthetics and can lead to complications such as hematoma, infections and even cancer cell ceding along the needle track. We show that by applying multicolor STED and image analysis, the information gained from single cells is greatly increased. We therefore propose that accurate diagnosis can be based on significantly less extracted tissue material, allowing for a more patient friendly sampling. This approach can also be applied when studying blood platelets, where we show how the high informational content can be used to identify platelet specific activational states. Since platelets are involved in many different types of diseases, such analysis could provide means of performing truly minimally invasive diagnostics based on a simple blood test. In addition, our data makes it possible to understand in finer detail the underlying mechanisms rendering cells metastasis competent. We combine the high resolution spatial information provided by STED with information regarding the adhesive forces of cells measured by TFM (Traction Force Microscopy) and the cell stiffness measured by AFM (Atomic Force Microscopy). Such comparisons provide a link between the specific highly resolved protein distributions and different cellular mechanics and functions. This thesis also includes STED imaging and analysis on the spatial organization of neuronal synaptic regulating proteins, implicating the speed with which neuronal signaling can be regulated.QC 20140207</p

Blood Pressure Levels and Longitudinal Changes in Relation to Social Network Factors

The aim of this study was to examine the relationship between social network variables and levels of and longitudinal changes in blood pressure in a middle-aged/older sample. The participants (50-75 years at baseline; n=1097) responded to questions concerning social relationships at baseline and their blood pressure (diastolic, systolic) was measured. Blood pressure levels were reassessed 5, 10, and 15 years later. Latent growth models with responses to questions concerning social relationships as predictors and basic demographic factors (age, sex) as covariates, unexpectedly indicated that a more limited social network (no close friend, few visits, little contact with friends in other ways, not living with someone, and a composite index based on all questions) was associated with significantly lower diastolic blood pressure levels. For systolic blood pressure a similar result was observed for one of the variables (lack of a close friend). In general, these effects diminished over time, as indexed by the positive relationship between several of the social variables and slope. The results were little affected by inclusion of additional covariates (e.g. measures of psychological distress, smoking/alcohol habits, and BMI) suggesting that the origins of this unexpected pattern of findings must probably be sought for in other subjectrelated factors, such as, for example, increased help seeking. Future studies should consider qualitative aspects (e.g. feelings of loneliness, quality of social relationships) in addition to structural aspects to provide a better understanding of these associations

Blood Pressure Levels and Longitudinal Changes in Relation to Social Network Factors

The aim of this study was to examine the relationship between social network variables and levels of and longitudinal changes in blood pressure in a middle-aged/older sample. The participants (50-75 years at baseline; n=1097) responded to questions concerning social relationships at baseline and their blood pressure (diastolic, systolic) was measured. Blood pressure levels were reassessed 5, 10, and 15 years later. Latent growth models with responses to questions concerning social relationships as predictors and basic demographic factors (age, sex) as covariates, unexpectedly indicated that a more limited social network (no close friend, few visits, little contact with friends in other ways, not living with someone, and a composite index based on all questions) was associated with significantly lower diastolic blood pressure levels. For systolic blood pressure a similar result was observed for one of the variables (lack of a close friend). In general, these effects diminished over time, as indexed by the positive relationship between several of the social variables and slope. The results were little affected by inclusion of additional covariates (e.g. measures of psychological distress, smoking/alcohol habits, and BMI) suggesting that the origins of this unexpected pattern of findings must probably be sought for in other subjectrelated factors, such as, for example, increased help seeking. Future studies should consider qualitative aspects (e.g. feelings of loneliness, quality of social relationships) in addition to structural aspects to provide a better understanding of these associations

Reading Habits Among Older Adults in Relation to Level and 15-Year Changes in Verbal Fluency and Episodic Recall

The main objective of this study was to investigate reading habits in older adults in relation to level and 15-year changes in verbal fluency and episodic recall. We examined a sample of 1157 participants (55 years at baseline) up to 15 years after the baseline assessment using latent growth curve modeling of cognitive measures with baseline reading frequency (books, weekly magazines) as a predictor of cognitive level (intercept) and rate of change (slope). Subgroup analyses were performed to investigate the role of an early adult g factor in the association between reading habits and cognitive ability in midlife. Frequent reading of books, but not of magazines, was associated with higher levels of verbal fluency and recall but unrelated to rate of longitudinal decline. Subgroup analyses indicated that the g factor in early adulthood predicted reading and cognitive level in midlife and this factor removed the current association between reading habits and level of cognitive ability (both cognitive factors). The results indicate an enduring relationship between book reading and level of cognitive ability across the adult life span and provide little support of the hypothesis that frequent reading protects against latelife cognitive decline. The extent to which book reading promotes cognitive functioning in childhood/youth remains to be demonstrated. Intervention studies may be useful in this regard

Scanning inverse fluorescence correlation spectroscopy

Scanning Inverse Fluorescence Correlation Spectroscopy (siFCS) is introduced to determine the absolute size of nanodomains on surfaces. We describe here equations for obtaining the domain size from cross-and auto-correlation functions, measurement simulations which enabled testing of these equations, and measurements on model surfaces mimicking membranes containing nanodomains. Using a confocal microscope of 270 nm resolution the size of 250 nm domains were estimated by siFCS to 257 +/- 12 nm diameter, and 40 nm domains were estimated to 65 +/- 26 nm diameter. Applications of siFCS for sizing of nanodomains and protein clusters in cell membranes are discussed.QC 20140808</p

Двухосевая система управления гидроаппаратом

Scanning Inverse Fluorescence Correlation Spectroscopy (siFCS) is introduced to determine the absolute size of nanodomains on surfaces. We describe here equations for obtaining the domain size from cross-and auto-correlation functions, measurement simulations which enabled testing of these equations, and measurements on model surfaces mimicking membranes containing nanodomains. Using a confocal microscope of 270 nm resolution the size of 250 nm domains were estimated by siFCS to 257 +/- 12 nm diameter, and 40 nm domains were estimated to 65 +/- 26 nm diameter. Applications of siFCS for sizing of nanodomains and protein clusters in cell membranes are discussed.QC 20140808</p