Monitoring radiotherapy with functional OCT: Microvascular responses and correlations with MRI

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Galaktosylierung und Sialinisierung von Immunglobulin G in Liquor und Serum von Patienten mit Multipler Sklerose

Multiple Sklerose ist eine entzündliche Erkrankung des zentralen Nervensystems (ZNS). Bei verschiedenen chronisch-entzündlichen Erkrankungen, wie beispielsweise der rheumatoiden Arthritis, wurden Veränderungen der Glykosylierung von Antikörpern festgestellt. Die Glykosylierung hat direkte Auswirkungen auf die Funktion der Antikörper. So nimmt beispielsweise die zellvermittelte Zytotoxität oder auch die Komplementsystem-Aktivierung ab. Ziel dieser Arbeit ist, zu untersuchen, ob die Multiple Sklerose, als chronisch-entzündliche Erkrankung, welche sich auf das zentrale Nervensystem beschränkt, auch mit Veränderungen der Glykosylierung einhergeht. Ebenfalls sollte untersucht werden, ob solche Veränderungen bei chronischen Entzündungen im Zentralnervensystem auftreten, welche mit einer viralen Meningitis einhergehen. Untersucht wurden Serum- und Liquorproben von Patienten mit Multipler Sklerose, viraler Meningitis sowie einer Kontrollgruppe ohne entzündliche Erkrankung oder Autoimmunerkrankung. Immunglobulin G wurde aus diesen Proben isoliert und anschließend auf Veränderungen bei der Glykosylierung mittels Lektin-Assay untersucht. Die Ergebnisse zeigten bei der Galaktosylierung von Immunglobulin G im Liquor von gesunden Probanden eine Abhängigkeit von Alter und Geschlecht. Desweiteren zeigte sich eine signifikante Abnahme der Galaktosylierung von Immunglobulin G im Liquor von Patienten mit Multipler Sklerose. Diese Veränderungen zeigten sich allerdings nicht im Serum der Patienten. Außerdem konnte eine Korrelation von Galaktosylierung und Progress der Krankheit gezeigt werden. Es konnte auch gezeigt werden, dass die abnehmende Galaktosylierung nicht einfach nur auf eine Entzündungsreaktion zurückzuführen ist, da keine solchen Veränderungen bei Patienten mit viraler Meningitis festgestellt werden konnten. Außerdem konnte gezeigt werden, dass die Sialinisierung von Immunglobulin G im Serum von Patienten mit Multipler Sklerose signifikant erhöht ist. Möglicherweise kann weitere zukünftige Forschung darauf aufbauen, dass es messbare Veränderungen bei der Glykosylierung von Immunglobulin G bei Patienten mit Multipler Sklerose gibt, um beispielsweise Marker für Krankheitsaktivität zu entwickeln oder neue Therapieoptionen zu schaffen.Abstract Title: Investigation of galactosylation and sialylation of immunoglobulin G in cerebrospinal fluid and serum of Multiple Sclerosis patients Multiple Sclerosis is an inflammatory disease of the central nervous system (CNS). Alterations in glycosylation of antibodys were discovered in various chronic inflammatory diseases, like rheumatoid arthritis. Glycosylation has a direct effect on antibody functions. For example, it can reduce antibodydependent cell-mediated cytotoxicity or activation of the complement system. Objective of this thesis is to examinate, if Multiple Sclerosis - a chronic inflammatory disease which constrains it’s inflammatory activity on the central nervous system - is also a disease effected by glycosylation changes in antibodys. Another goal is to find out, if such changes in glycosylation also occur in other states of chronic inflammation in the CNS, like Viral Meninigitis. Serum and cerebrospinal fluid (CSF) samples from patients with Multiple Sclerosis and Viral Meningitis were analyzed and compared to a control group of healthy probands without any inflammatory or autoimmune disease. Immunoglobulin G (IgG) was isolated from the samples and a lectin-based assay was used to investigate potential alterations of glycosylation. Results showed that galactosylation of Immunoglobulin G in CSF is dependent on age and gender. Furthermore a significant decrease in galactosylation of IgG in CSF of Multiple Sclerosis patients could be shown, which could not be found in serum samples of patients. Additionally a correlation between galactosylation and disease progression could be indicated. Loss of galactose residues is not simply result of inflammation, since no significat differences could be shown in Viral Meningitis patients. Furthermore a significant increase of sialysation of IgG could be shown in serum of Multiple Sclerosis patients. The task of future research will be to find out if this measurable glycosylation changes can be utilized as markers for disease activity or for development of new therapy options

Model-based Development for Event-driven Applications using MATLAB: Audio Playback Case Study

Audio playbacks are mechanisms which read data from a storage medium and produce commands and signals which an audio system turns into music. Playbacks are constantly changed to meet market demands, requiring that the control software be updated quickly and efficiently

Executable Specs: What Makes One, and How are They Used?

Model-based systems development relies upon the concept of an executable specification. A survey of published literature shows a wide range of definitions for executable specifications [1-10]. In this paper, we attempt to codify the essential starting elements for a complete executable specification-based design flow. A complete executable specification that includes a functional model as well as test cases, in addition to a traditional prose document, is needed to transfer requirements from a customer to a supplier, or from a systems engineer to electrical hardware and software engineers. In the complete form demonstrated here, sub-components of a functionally-decomposed system manifest as modular reuse blocks suitable for publication in functional libraries. The overarching definition provided by product architecture and by software architecture must also be harmoniously integrated with design and implementation. Using seven specific automotive examples, we illustrate effective ways in which executable specifications have been used in production-ready applications. Benefits of model-based development are captured, including earlier and more thorough testing, automatic document generation, and autocode generation

Non-invasive voiding assessment in conscious mice

OBJECTIVE: To review available options of assessing murine bladder function and to evaluate a non-invasive technique suitable for long-term recording. METHODS: We reviewed previously described methods to record rodent bladder function. We used modified metabolic cages to capture novel recording tracings of mouse micturition. We evaluated our method in a pilot study with female mice undergoing partial bladder outlet obstruction or sham operation, respectively; half of the partial obstruction and sham group received treatment with an S6K-inhibitor, targeting the mTOR pathway, which is known to be implicated in bladder response to obstruction. RESULTS: Our non-invasive method using continuous urine weight recording reliably detected changes in murine bladder function resulting from partial bladder outlet obstruction or treatment with S6K-inhibitor. We found obstruction as well as treatment with S6K-inhibitor to correlate with a hyperactive voiding pattern. CONCLUSIONS: While invasive methods to assess murine bladder function largely disturb bladder histology and intrinsically render post-cystometry gene expression analysis of questionable value, continuous urine weight recording is a reliable, inexpensive, and critically non-invasive method to assess murine bladder function, suitable for a long-term application

Quantitative photoluminescence of broad band absorbing melanins: A procedure to correct for inner filter and re-absorption effects

We report methods for correcting the photoluminescence emission and excitation spectra of highly absorbing samples for re-absorption and inner filter effects. We derive the general form of the correction, and investigate various methods for determining the parameters. Additionally, the correction methods are tested with highly absorbing fluorescein and melanin (broadband absorption) solutions; the expected linear relationships between absorption and emission are recovered upon application of the correction, indicating that the methods are valid. These procedures allow accurate quantitative analysis of the emission of low quantum yield samples (such as melanin) at concentrations where absorption is significant.Comment: 20 pages, 13 figure

Polarized light microscopy for quantitative assessment of colorectal cancer: Can we predict local recurrence?

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Preclinical quantitative in-vivo assessment of skin tissue vascularity in radiation-induced fibrosis with optical coherence tomography.

Radiation therapy (RT) is widely and effectively used for cancer treatment but can also cause deleterious side effects, such as a late-toxicity complication called radiation-induced fibrosis (RIF). Accurate diagnosis of RIF requires analysis of histological sections to assess extracellular matrix infiltration. This is invasive, prone to sampling limitations, and thus rarely used; instead, current practice relies on subjective clinical surrogates, including visual observation, palpation, and patient symptomatology questionnaires. This preclinical study demonstrates that functional optical coherence tomography (OCT) is a useful tool for objective noninvasive in-vivo assessment and quantification of fibrosis-associated microvascular changes in tissue. Data were collected from murine hind limbs 6 months after 40-Gy single-dose irradiation and compared with nonirradiated contralateral tissues of the same animals. OCT-derived vascular density and average vessel diameter metrics were compared to quantitative vascular analysis of stained histological slides. Results indicate that RIF manifests significant microvascular changes at this time point posttreatment. Abnormal microvascular changes visualized by OCT in this preclinical setting suggest the potential of this label-free high-resolution noninvasive functional imaging methodology for RIF diagnosis and assessment in the context of clinical RT