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Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.
The complementary advantages of high-rate Global Positioning System (GPS) and accelerometer observations for measuring seismic ground motion have been recognised in previous research. Here we propose an approach of tight integration of GPS and accelerometer measurements. The baseline shifts of the accelerometer are introduced as unknown parameters and estimated by a random walk process in the Precise Point Positioning (PPP) solution. To demonstrate the performance of the new strategy, we carried out several experiments using collocated GPS and accelerometer. The experimental results show that the baseline shifts of the accelerometer are automatically corrected, and high precision coseismic information of strong ground motion can be obtained in real-time. Additionally, the convergence and precision of the PPP is improved by the combined solution.
Objective:
Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF).
Methods:
The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment.
Results:
Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS.
Conclusion:
Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF.
The European potential for renewable electricity is sufficient to enable fully renewable supply on different scales, from self-sufficient, subnational regions to an interconnected continent. We not only show that a continental-scale system is the cheapest, but also that systems on the national scale and below are possible at cost penalties of 20% or less. Transmission is key to low cost, but it is not necessary to vastly expand the transmission system. When electricity is transmitted only to balance fluctuations, the transmission grid size is comparable to today's, albeit with expanded cross-border capacities. The largest differences across scales concern land use and thus social acceptance: in the continental system, generation capacity is concentrated on the European periphery, where the best resources are. Regional systems, in contrast, have more dispersed generation. The key trade-off is therefore not between geographic scale and cost, but between scale and the spatial distribution of required generation and transmission infrastructure.
Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor
(2010)
Background and purpose: 5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT1 receptor of an insect model for neurobiology, physiology and pharmacology. Experimental approach: A cDNA encoding for the Periplaneta americana 5-HT1 receptor was amplified from brain cDNA. The receptor was stably expressed in HEK 293 cells, and the functional and pharmacological properties were determined in cAMP assays. Receptor distribution was investigated by RT-PCR and by immunocytochemistry using an affinity-purified polyclonal antiserum. Key results: The P. americana 5-HT1 receptor (Pea5-HT1) shares pronounced sequence and functional similarity with mammalian 5-HT1 receptors. Activation with 5-HT reduced adenylyl cyclase activity in a dose-dependent manner. Pea5-HT1 was expressed as a constitutively active receptor with methiothepin acting as a neutral antagonist, and WAY 100635 as an inverse agonist. Receptor mRNA was present in various tissues including brain, salivary glands and midgut. Receptor-specific antibodies showed that the native protein was expressed in a glycosylated form in membrane samples of brain and salivary glands. Conclusions and implications: This study marks the first pharmacological identification of an inverse agonist and a neutral antagonist at an insect 5-HT1 receptor. The results presented here should facilitate further analyses of 5-HT1 receptors in mediating central and peripheral effects of 5-HT in insects.
Der gemeinsame Wandel der inselkeltischen Sprachen wie auch des Englischen vom vorwiegend synthetischen Typus zum vorwiegend analytischen Typus läßt sich vermutlich auf einen ca. 1500 Jahre dauernden intensiven Sprachenkontakt zwischen diesen Sprachen zurückführen. Heute ist das Englische die analytischste Sprache der Britischen Inseln und Irlands, gefolgt vom Walisischen, Bretonischen und Irischen. Letzteres ist von den genannten Sprachen noch am weitesten morphologisch komplex.
This paper argues that the texts surviving from the Old English period do not reflect the spoken language of the bulk of the population under Anglo-Saxon elite domination. While the Old English written documents suggest that the language was kept remarkably unchanged, i.e. was strongly monitored during the long OE period (some 500 years!), the spoken and "real Old English" is likely to have been very different and much more of the type of Middle English than the written texts. "Real Old Engish", i.e. of course only appeared in writing after the Norman Conquest. Middle English is therefore claimed to have begun with the 'late British' speaking shifters to Old English. The shift patterns must have differed in the various part of the island of Britain, as the shifters became exposed to further language contact with the Old Norse adstrate in the Danelaw areas and the Norman superstrate particularly in the South East, the South West having been least exposed to language contact after the original shift from 'Late British' to Old English. This explains why the North was historically the most innovative zone. This also explains the conservatism of the present day dialects in the South West. It is high time that historical linguists acknowledge the arcane character of the Old English written texts.
Fontanes Medien
(2023)
Theodor Fontane war, im durchaus modernen Sinne, ein Medienarbeiter: Als Presse-Agent in London lernte er die innovativste Presselandschaft seiner Zeit kennen; als Redakteur in Berlin leistete er journalistische Kärrnerarbeit; er schrieb Kritiken über das Theater, die bildende Kunst und die Literatur – und auch seine Romane wie seine Reisebücher sind stets Medienprodukte, als Serien in in Zeitungen und Zeitschriften platziert, bevor sie auf dem Buchmarkt erschienen.
Der vorliegende Band dokumentiert die Ergebnisse eines internationalen Kongresses, veranstaltet 2019 vom Theodor-Fontane-Archiv in Potsdam. Die ebenso rasante wie umfassende Medialisierung und Vernetzung der Gesellschaft im Laufe des 19. Jahrhunderts wird dabei als produktive Voraussetzung der schriftstellerischen Tätigkeit Fontanes begriffen. Eingebettet in ein weit verzweigtes Netz der Korrespondenz und der postalischen Textzirkulation, vertraut mit den Routinen und Publika der periodischen Massenpresse, für die er sein Leben lang schrieb, und auf vielfältige Weise geprägt von der visuellen Kultur seiner Zeit wird Theodor Fontane als gleichermaßen journalistisch versierter wie ästhetisch sensibler Grenzgänger erkennbar.
Flooding is an imminent natural hazard threatening most river deltas, e.g. the Mekong Delta. An appropriate flood management is thus required for a sustainable development of the often densely populated regions. Recently, the traditional event-based hazard control shifted towards a risk management approach in many regions, driven by intensive research leading to new legal regulation on flood management. However, a large-scale flood risk assessment does not exist for the Mekong Delta. Particularly, flood risk to paddy rice cultivation, the most important economic activity in the delta, has not been performed yet. Therefore, the present study was developed to provide the very first insight into delta-scale flood damages and risks to rice cultivation. The flood hazard was quantified by probabilistic flood hazard maps of the whole delta using a bivariate extreme value statistics, synthetic flood hydrographs, and a large-scale hydraulic model. The flood risk to paddy rice was then quantified considering cropping calendars, rice phenology, and harvest times based on a time series of enhanced vegetation index (EVI) derived from MODIS satellite data, and a published rice flood damage function. The proposed concept provided flood risk maps to paddy rice for the Mekong Delta in terms of expected annual damage. The presented concept can be used as a blueprint for regions facing similar problems due to its generic approach. Furthermore, the changes in flood risk to paddy rice caused by changes in land use currently under discussion in the Mekong Delta were estimated. Two land-use scenarios either intensifying or reducing rice cropping were considered, and the changes in risk were presented in spatially explicit flood risk maps. The basic risk maps could serve as guidance for the authorities to develop spatially explicit flood management and mitigation plans for the delta. The land-use change risk maps could further be used for adaptive risk management plans and as a basis for a cost-benefit of the discussed land-use change scenarios. Additionally, the damage and risks maps may support the recently initiated agricultural insurance programme in Vietnam.
Inertial measurement units (IMUs) enable easy to operate and low-cost data recording for gait analysis. When combined with treadmill walking, a large number of steps can be collected in a controlled environment without the need of a dedicated gait analysis laboratory. In order to evaluate existing and novel IMU-based gait analysis algorithms for treadmill walking, a reference dataset that includes IMU data as well as reliable ground truth measurements for multiple participants and walking speeds is needed. This article provides a reference dataset consisting of 15 healthy young adults who walked on a treadmill at three different speeds. Data were acquired using seven IMUs placed on the lower body, two different reference systems (Zebris FDMT-HQ and OptoGait), and two RGB cameras. Additionally, in order to validate an existing IMU-based gait analysis algorithm using the dataset, an adaptable modular data analysis pipeline was built. Our results show agreement between the pressure-sensitive Zebris and the photoelectric OptoGait system (r = 0.99), demonstrating the quality of our reference data. As a use case, the performance of an algorithm originally designed for overground walking was tested on treadmill data using the data pipeline. The accuracy of stride length and stride time estimations was comparable to that reported in other studies with overground data, indicating that the algorithm is equally applicable to treadmill data. The Python source code of the data pipeline is publicly available, and the dataset will be provided by the authors upon request, enabling future evaluations of IMU gait analysis algorithms without the need of recording new data.