Bestimmung elastischer und viskoelastischer Kenngrößen von Knochenproben unter Langzeitkultur-Bedingungen mit einem neuartigen softwaregesteuerten elektro-mechanischen Belastungs- und Messsystem

Die Arbeit beschreibt zunächst die Entwicklung eines Messsystems (sog. ZETOS-System) zur Bestimmung der Steifigkeit (dargestellt als Elastizitätsmodul) von Knochenproben in Langzeit-Bioreaktoren. Dieses System ermöglicht auch dynamische Stimulationen der Knochen mit Standard-Signalen (Sinus, Rechteck) sowie die Verwendung von beliebigen oder typischen physiologischen Signalen, wie z.B. „Gehen“, „Springen“ und „Laufen“, aufgenommen als sog. Gound-Reaction Forces, zur mechanischen Knochenstimulation. Optional können Softwarefilter (Hochpass, Tiefpass) eingeschaltet werden. Aufgrund der eindimensionalen Messung und Belastung kann der elastische Tensor nicht vollständig bestimmt werden. In einer Langzeitmessreihe wurden Trabekel-Knochenproben aus einem humanen Hüftkopf mit dem physiologischen Signal „Springen“ 5 Minuten pro Tag stimuliert. Es zeigte sich eine deutliche Zunahme der Steifigkeit von fast 2%/Tag, während die Knochen einer Kontrollgruppe unverändert blieben. Eine dritte Gruppe von Knochenproben wurde ebenfalls mit „Springen“, jedoch Hochpass gefiltert stimuliert. Durch die fast gleiche Zunahme der Steifigkeit dieser Knochen wurde anhand des Signals „Springen“ gezeigt, dass allein höherfrequente Spektralanteile für bone-remodeling ausreichend sind. Mit den Daten dieser Messreihe wurde erstmals die Frage der Entstehung und Bedeutung des nichtlinearen Verkaufs der Messkurven (Kompression gegen Kraft) des ZETOS-Systems durch die Existenz der von mir genannten „Kontaktflächenfunktion“ beantwortet. Dieser Effekt entsteht durch Rauhigkeiten der Schnittfläche – dem Oberflächenkontakt. Modellrechnungen erklären folgendes: - eine grobe Abschätzung der Standardabweichung der Rauhigkeit der Schnittflächen - den Unterschied zwischen der außen gemessen Dehnung und der Dehnung im Knochenkern - die Unmöglichkeit der Bestimmung des wahren Elastizitätsmoduls des kalzifierten Anteils der Knochenkörper (der als linear im üblichen Sinne betrachtet werden darf) aus der Tatsache, dass die Dehnung mit Rücksicht auf die Vermeidung physiologischer Überlast auf kleine Werte beschränkt sein muss. Die Messdaten wurden zusätzlich numerisch wie folgt verarbeitet: - erste Ableitung Kompression gegen Kraft (kraftabhängige Nachgiebigkeit): Daraus wurde eine Methode zur Bestimmung der Kontaktflächenfunktion aus Messdaten abgeleitet. Es zeigte sich, dass diese Funktion keine strenge Invariante über den gesamten Messzeitraum und an der Veränderung des Messwertes des Elastizitätsmoduls wahrscheinlich beteiligt ist. Dieser Effekt ist aber nur schwach. - Integration (potentielle Energie): Daraus entstand eine alternative Methode zur Bestimmung des Elastizitätsmoduls, die mit Einschränkungen eine simultane Anwendung der Messung des scheinbaren Elastizitätsmoduls während dynamischer Stimulation erlaubt. Während der Langzeitmessreihe wurden auch Relaxationsmessungen vorgenommen. Dabei wurden zwei Zeitkonstanten festgestellt: im Mittel bei 0,4 und bei 20 Sekunden. Die kleinere der beiden Zeitkonstanten muss in ihrer Umgebung in ein kontinuierliches Relaxationszeitenspektrum entwickelt werden, um den gemessenen zeitlichen Kraftverlauf bei Relaxation richtig approximieren zu können. Die Datenverarbeitung erlaubt u.a. die Darstellung der Frequenzabhängigkeit des Speicher- und des Verlustmoduls sowie den Verlustfaktor und die Phasendifferenz zwischen Kompression und Kraft im Falle harmonischer Anregung. Für die Messung des statischen (relaxationsfreien) Elastizitätsmoduls entsteht die Forderung einer Messzeit von ca. 3 Minuten. Beim Vergleich der Modulspektren aus Relaxationsmessung mit den Spektren der physiologischen Stimulationssignale zeigte sich eine Selektivität der Knochen: Energiedissipation tritt bei „Gehen“ und „Springen“ auf, im Falle von „Laufen“ jedoch deutlich schwächer, was vermutlich der Ausdauer beim Laufen (Flucht-, Jagd-, Angriffsverhalten) dienen soll

Hyperthermic Isolated Limb Perfusion with TNF α and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management of osteosarcoma was studied in the canine model

Imaging Predictors of Left Ventricular Functional Recovery after Reperfusion Therapy of ST-Elevation Myocardial Infarction Assessed by Cardiac Magnetic Resonance

Background: Left ventricular global longitudinal strain (LV GLS) is a superior predictor of adverse cardiac events in patients with myocardial infarction and heart failure. We investigated the ability of morphological features of infarcted myocardium to detect acute left ventricular (LV) dysfunction and predict LV functional recovery after three months in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: Sixty-six STEMI patients were included in the C-reactive protein (CRP) apheresis in Acute Myocardial Infarction Study (CAMI-1). LV ejection fraction (LVEF), LV GLS, LV global circumferential strain (LV GCS), infarct size (IS), area-at-risk (AAR), and myocardial salvage index (MSI) were assessed by CMR 5 ± 3 days (baseline) and 12 ± 2 weeks after (follow-up) the diagnosis of first acute STEMI. Results: Significant changes in myocardial injury parameters were identified after 12 weeks of STEMI diagnosis. IS decreased from 23.59 ± 11.69% at baseline to 18.29 ± 8.32% at follow-up (p < 0.001). AAR and MVO also significantly reduced after 12 weeks. At baseline, there were reasonably moderate correlations between IS and LVEF (r = −0.479, p < 0.001), LV GLS (r = 0.441, p < 0.001) and LV GCS (r = 0.396, p = 0.001) as well as between AAR and LVEF (r = −0.430, p = 0.003), LV GLS (r = 0.501, p < 0.001) and weak with LV GCS (r = 0.342, p = 0.020). At follow-up, only MSI and change in LV GCS over time showed a weak but significant correlation (r = −0.347, p = 0.021). Patients with larger AAR at baseline improved more in LVEF (p = 0.019) and LV GLS (p = 0.020) but not in LV GCS. Conclusion: The CMR tissue characteristics of myocardial injury correlate with the magnitude of LV dysfunction during the acute stage of STEMI. AAR predicts improvement in LVEF and LV GLS, while MSI is a sensitive marker of LV GCS recovery at three months follow-up after STEMI

Decreasing trends of particle number and black carbon mass concentrations at 16 observational sites in Germany from 2009 to 2018

Anthropogenic emissions are dominant contributors to air pollution. Consequently, mitigation policies have been attempted since the 1990s in Europe to reduce pollution by anthropogenic emissions. To evaluate the effectiveness of these mitigation policies, the German Ultrafine Aerosol Network (GUAN) was established in 2008, focusing on black carbon (BC) and sub-micrometre aerosol particles. In this study, long-term trends of atmospheric particle number concentrations (PNCs) and equivalent BC (eBC) mass concentration over a 10-year period (2009-2018) were determined for 16 GUAN sites ranging from roadside to high Alpine environments. Overall, statistically significant decreasing trends are found for most of these parameters and environments in Germany. The annual relative slope of eBC mass concentration varies between-13.1% and-1.7% per year. The slopes of the PNCs vary from-17.2% to-1.7 %,-7.8% to-1.1 %, and-11.1% to-1.2% per year for 10-30, 30-200, and 200-800 nm size ranges, respectively. The reductions in various anthropogenic emissions are found to be the dominant factors responsible for the decreasing trends of eBC mass concentration and PNCs. The diurnal and seasonal variations in the trends clearly show the effects of the mitigation policies for road transport and residential emissions. The influences of other factors such as air masses, precipitation, and temperature were also examined and found to be less important or negligible. This study proves that a combination of emission mitigation policies can effectively improve the air quality on large spatial scales. It also suggests that a long-term aerosol measurement network at multi-type sites is an efficient and necessary tool for evaluating emission mitigation policies. © 2020 Author(s)

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.</p

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype.</p

Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity

Utilizing trio whole-exome sequencing and a gene matching approach, we identified a cohort of 18 male individuals from 17 families with hemizygous variants in KCND1, including two de novo missense variants, three maternally inherited protein-truncating variants, and 12 maternally inherited missense variants. Affected subjects present with a neurodevelopmental disorder characterized by diverse neurological abnormalities, mostly delays in different developmental domains, but also distinct neuropsychiatric signs and epilepsy. Heterozygous carrier mothers are clinically unaffected. KCND1 encodes the α-subunit of Kv4.1 voltage-gated potassium channels. All variant-associated amino acid substitutions affect either the cytoplasmic N- or C-terminus of the channel protein except for two occurring in transmembrane segments 1 and 4. Kv4.1 channels were functionally characterized in the absence and presence of auxiliary β subunits. Variant-specific alterations of biophysical channel properties were diverse and varied in magnitude. Genetic data analysis in combination with our functional assessment shows that Kv4.1 channel dysfunction is involved in the pathogenesis of an X-linked neurodevelopmental disorder frequently associated with a variable neuropsychiatric clinical phenotype

Increasing the Brightness of Light Sources

In modern illumination systems, compact size and high brightness are important features. Light recycling allows an increase of the spectral radiance (brightness) emitted by a light source for the price of reducing the total radiant power. Light recycling means returning part of the emitted light to the source where part of it will escape absorption. As a result, the output brightness can be increased in a restricted phase space, compared with the intrinsic brightness of the source. In this work the principle of light recycling is applied to artificial light sources in order to achieve brightness enhancement. Firstly, the feasibilities of increasing the brightness of light sources via light recycling are examined theoretically, based on the fundamental laws of thermodynamics including Kirchhoff's law on radiation, Planck's law, Lambert-Beer's law, the étendue conservation and the brightness theorem. The theory of light recycling can be derived from first principles. From an experimental viewpoint, the radiation properties of three different kinds of light sources including short-arc lamps, incandescent lamps and LEDs characterized by their light-generating mechanisms are investigated. These three types of sources are used in light recycling experiments, for the purpose of 1. validating the intrinsic light recycling effect in light sources, e. g. the intrinsic light recycling effect in incandescent lamps stemming from the coiled filament structure. 2. acquiring the required parameters for establishing physical models, e.g. the emissivity/absorptivity of the short-arc lamps, the intrinsic reflectivity and the external quantum efficiency of LEDs. 3. laying the foundations for designing optics aimed at brightness enhancement according to the characteristics of the sources and applications. Based on the fundamental laws and experiments, two physical models for simulating the radiance distribution of light sources are established, one for thermal filament lamps, the other for luminescent sources, LEDs. Both are validated with high resolution measurements. The physical models are capable of analytically modelling the radiance distribution with few required parameters (geometry, material properties and operating conditions). They are widely applicable to any kind of sources with similar light-emitting mechanisms. Combining the advantages of conciseness, high accuracy and wide applicability, the physical models can be integrated into ray-tracing software. As validation of the theoretical and experimental investigation of the light recycling effect, an optical device, the Carambola, is designed for achieving deterministic (as opposed to stochastic) and multiple light recycling. The Carambola has the function of a concentrator. In order to achieve the maximum possible brightness enhancement with the Carambola, several combinations of sources and Carambolas are modelled in ray-tracing simulations. Sources with different light-emitting mechanisms and different radiation properties (optical thickness), and Carambolas with different geometries and optical properties are used. It is concluded that a high-pressure xenon lamp is suitable for light recycling with the Carambola due to its moderate optical thickness, its continuous spectrum and its geometrical features. In the ray-tracing simulation, the suitability of the XBO lamp and the Carambola optics for light recycling is confirmed. A prototype five-point reflective Carambola was manufactured from aluminium, for the purpose of experimentally demonstrating a brightness increase. The Carambola is tested with different sources. The experimental results are below the theoretical expectation, i.e. the measured brightness enhancement factor is lower than the designed factor and the modelled factor. The discrepancies are explained. A real Carambola must have a high reflectivity and an accurate shape, if a significant effect of light recycling is to be shown. The brightness enhancement by light recycling with the Carambola is expected to be improved greatly by enhancing the surface quality of the reflectors, using suitable sources with small optical thickness, compact size, (and in the case of LEDs) high intrinsic reflectivity and external quantum efficiency. The Carambola is expected to be utilized in applications such as high brightness displays. In conclusion, both theoretical investigation and experimental measurements on light recycling demonstrated a significant increase of the brightness of optically thin sources