Biochemistry of the Phagosome: The Challenge to Study a Transient Organelle

Phagocytes are specialized cells of the immune system, designed to engulf and destroy harmful microorganisms inside the newly formed phagosome. The latter is an intracellular organelle that is transformed into a toxic environment within minutes and disappears once the pathogen is destroyed. Reactive oxygen species and reactive nitrogen species are produced inside the phagosome. Intracellular granules or lysosomes of the phagocyte fuse with the phagosome and liberate their destructive enzymes. This process of phagocytosis efficiently protects against most infections; however, some microorganisms avoid their destruction and cause severe damage. To understand such failure of phagosomal killing, we need to learn more about the actual destruction process in the phagosome. This paper summarizes methods to investigate the biochemistry of the phagosome and discusses some of their limitations. In accordance with the nature of the phagosome, the issue of localization and temporal dynamics is emphasized, and recent developments are highlighted

Application of machine learning for the extrapolation of seismic data

Low frequencies in seismic data are often challenging to acquire. Without low frequencies, though, a method like full-waveform inversion might fail due to cycle-skipping. This thesis aims to investigate the potential of neural networks for the task of low-frequency extrapolation to overcome aforementioned problem. Several steps are needed to achieve this goal: First, suitable data for training and testing the network must be found. Second, the data must be pre-processed to condition them for machine learning and efficient application. Third, a specific workflow for the task of low-frequency extrapolation must be designed. Finally, the trained network can be applied to data it has not seen before and compared to reference data. In this work, synthetic data are used for training and evaluation because in such a controlled experiment the target for the network is known. For this purpose, 30 random but geologically plausible subsurface models were generated based on a simplified geology around the Asse II salt mine, and used for finite-difference simulations of seismograms. The corresponding shot gathers were pre-processed by, among others, normalizing them and splitting them up into patches, and fed into a convolutional neural network (U-Net) to assess the network’s performance and its ability to reconstruct the data. Two different approaches were investigated for the task of low-frequency extrapolation. The first approach is based on using only low frequencies as the network’s target, while the second approach has the full bandwidth as target. The latter yielded superior results and was therefore chosen for subsequent applications. Further tests of the network design led to the introduction of ResNet blocks instead of simple convolutions in the U-Net layers, and the use of the mean-absolute-error instead of the mean-squared-error loss function. The final network designed in this way was then applied to the synthetic data originally reserved for testing. It turned out that the chosen method is able to successfully extrapolate low frequencies by more than half an octave (from about 8 to 5 Hz) given the experimental setup at hand. Although the results start to deteriorate in the low-frequency band for larger offsets, full-waveform inversion will overall benefit from the application of the presented machine learning approach

Kinetics of radiation- and cytochrome c-induced modifications in liposomes analysed by FT–Raman spectroscopy

AbstractFourier transform Raman spectroscopy on artificial lipid membranes was used to study radiation-induced peroxidation processes as a function of time after radiation exposure. The time dependent intensity changes of the Raman lines of various CC bondings were compared to results obtained by measuring conjugated dienes and by the thiobarbituric acid test for malondialdehydes. The results show that mainly the cis CC bonds of the lipid chains are involved and, therefore, indicate that γ-radiation induces conformational changes in the lipid chain while the mobility of the lipid chains is reduced. New Raman bands can be assigned to aldehyde products induced at the end of the peroxidation process. The immediate decrease of the CH vibration lines was directly correlated with the formation of conjugated CC double bonds suggesting that these vibration lines are in contrast to the CC lines solely Raman active, when isolated CC bonds are present. Cytochrome c (ox.) incorporated into the bilayer of the artificial membranes induced autooxidation processes not influenced by γ-radiation. It was observed that cytochrome c (ox.)-induced changes of the relative intensity of the CC bonds differ from those induced by γ-radiation. These results of cytochrome c together with the inhibitory effects of the antioxidant α-tocopherol suggest that the radical species involved in the cytochrome c induced process might be different from the free radicals involved in the γ-radiation-induced process

Enhancement of the Zero Phonon Line emission from a Single NV-Center in a Nanodiamond via Coupling to a Photonic Crystal Cavity

Using a nanomanipulation technique a nanodiamond with a single nitrogen vacancy center is placed directly on the surface of a gallium phosphide photonic crystal cavity. A Purcell-enhancement of the fluorescence emission at the zero phonon line (ZPL) by a factor of 12.1 is observed. The ZPL coupling is a first crucial step towards future diamond-based integrated quantum optical devices

A Novel H+ Conductance in Eosinophils: Unique Characteristics and Absence in Chronic Granulomatous Disease

Efficient mechanisms of H+ ion extrusion are crucial for normal NADPH oxidase function. However, whether the NADPH oxidase—in analogy with mitochondrial cytochromes—has an inherent H+ channel activity remains uncertain: electrophysiological studies did not find altered H+ currents in cells from patients with chronic granulomatous disease (CGD), challenging earlier reports in intact cells. In this study, we describe the presence of two different types of H+ currents in human eosinophils. The “classical” H+ current had properties similar to previously described H+ conductances and was present in CGD cells. In contrast, the “novel” type of H+ current had not been described previously and displayed unique properties: (a) it was absent in cells from gp91- or p47-deficient CGD patients; (b) it was only observed under experimental conditions that allowed NADPH oxidase activation; (c) because of its low threshold of voltage activation, it allowed proton influx and cytosolic acidification; (d) it activated faster and deactivated with slower and distinct kinetics than the classical H+ currents; and (e) it was ∼20-fold more sensitive to Zn2+ and was blocked by the histidine-reactive agent, diethylpyrocarbonate (DEPC). In summary, our results demonstrate that the NADPH oxidase or a closely associated protein provides a novel type of H+ conductance during phagocyte activation. The unique properties of this conductance suggest that its physiological function is not restricted to H+ extrusion and repolarization, but might include depolarization, pH-dependent signal termination, and determination of the phagosomal pH set point

Расчет ГИН по схеме Аркадьева-Маркса

Объектом исследования является генератор импульсного напряжения по схеме Аркадьева-Маркса. Цель работы: спроектировать и рассчитать генератор импульсных напряжений. В процессе работы рассчитаны количественные значения элементов ГИНа: значения коэффициентов использования разрядной схемы и волны; емкость и индуктивность конденсатора; количество ступеней; фронтовое и разрядное сопротивления. Был выполнен расчет ресурсов, ставки налогов, отчислений. Так же было описаны рабочее место и законодательные и нормативные документы.The object of study is the generator of pulse voltage according to the scheme Arkadiev-Marx. Objective: to design and calculate the voltage impulse generator. In the process, the calculated quantitative values of the elements of a Hin: the coefficients of use of the discharge circuit and wave; the capacitance and inductance of the capacitor; number of steps; the front and discharge resistors. Calculated resources, tax rates, deductions. As described workplace and legislative and regulatory documents

Mesodermal fate decisions of a stem cell: the Wnt switch

Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis