600 Technik, Technologie
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The "Lomonosov" space project is lead by Lomonosov Moscow State University in collaboration with the following key partners: Joint Institute for Nuclear Research, Russia, University of California, Los Angeles (USA), University of Pueblo (Mexico), Sungkyunkwan University (Republic of Korea) and with Russian space industry organi-zations to study some of extreme phenomena in space related to astrophysics, astroparticle physics, space physics, and space biology. The primary goals of this experiment are to study:
-Ultra-high energy cosmic rays (UHECR) in the energy range of the Greizen-ZatsepinKuzmin (GZK) cutoff;
-Ultraviolet (UV) transient luminous events in the upper atmosphere;
-Multi-wavelength study of gamma-ray bursts in visible, UV, gamma, and X-rays;
-Energetic trapped and precipitated radiation (electrons and protons) at low-Earth orbit (LEO) in connection with global geomagnetic disturbances;
-Multicomponent radiation doses along the orbit of spacecraft under different geomagnetic conditions and testing of space segments of optical observations of space-debris and other space objects;
-Instrumental vestibular-sensor conflict of zero-gravity phenomena during space flight.
This paper is directed towards the general description of both scientific goals of the project and scientific equipment on board the satellite. The following papers of this issue are devoted to detailed descriptions of scientific instruments.
The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context. For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. The stably transfected myeloma cell line was used for the generation of hybridoma cells and an antigen- and isotype-specific screening method was established. The system has been validated for globular protein antigens as well as for haptens and enables a fast and early stage selection and validation of monoclonal antibodies in one step.
The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context. For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. The stably transfected myeloma cell line was used for the generation of hybridoma cells and an antigen- and isotype-specific screening method was established. The system has been validated for globular protein antigens as well as for haptens and enables a fast and early stage selection and validation of monoclonal antibodies in one step.
Cell-free protein synthesis as a novel tool for directed glycoengineering of active erythropoietin
(2018)
As one of the most complex post-translational modification, glycosylation is widely involved in cell adhesion, cell proliferation and immune response. Nevertheless glycoproteins with an identical polypeptide backbone mostly differ in their glycosylation patterns. Due to this heterogeneity, the mapping of different glycosylation patterns to their associated function is nearly impossible. In the last years, glycoengineering tools including cell line engineering, chemoenzymatic remodeling and site-specific glycosylation have attracted increasing interest. The therapeutic hormone erythropoietin (EPO) has been investigated in particular by various groups to establish a production process resulting in a defined glycosylation pattern. However commercially available recombinant human EPO shows batch-to-batch variations in its glycoforms. Therefore we present an alternative method for the synthesis of active glycosylated EPO with an engineered O-glycosylation site by combining eukaryotic cell-free protein synthesis and site-directed incorporation of non-canonical amino acids with subsequent chemoselective modifications.
The in‐depth understanding of charge carrier photogeneration and recombination mechanisms in organic solar cells is still an ongoing effort. In donor:acceptor (bulk) heterojunction organic solar cells, charge photogeneration and recombination are inter‐related via the kinetics of charge transfer states—being singlet or triplet states. Although high‐charge‐photogeneration quantum yields are achieved in many donor:acceptor systems, only very few systems show significantly reduced bimolecular recombination relative to the rate of free carrier encounters, in low‐mobility systems. This is a serious limitation for the industrialization of organic solar cells, in particular when aiming at thick active layers. Herein, a meta‐analysis of the device performance of numerous bulk heterojunction organic solar cells is presented for which field‐dependent photogeneration, charge carrier mobility, and fill factor are determined. Herein, a “spin‐related factor” that is dependent on the ratio of back electron transfer of the triplet charge transfer (CT) states to the decay rate of the singlet CT states is introduced. It is shown that this factor links the recombination reduction factor to charge‐generation efficiency. As a consequence, it is only in the systems with very efficient charge generation and very fast CT dissociation that free carrier recombination is strongly suppressed, regardless of the spin‐related factor.
Dendritic hPG-amid-C18-mPEG core-multishell nanocarriers (CMS) represent a novel class of unimolecular micelles that hold great potential as drug transporters, e. g., to facilitate topical therapy in skin diseases. Atopic dermatitis is among the most common inflammatory skin disorders with complex barrier alterations which may affect the efficacy of topical treatment.
Here, we tested the penetration behavior and identified target structures of unloaded CMS after topical administration in healthy mice and in mice with oxazolone-induced atopic dermatitis. We further examined whole body distribution and possible systemic side effects after simulating high dosage dermal penetration by subcutaneous injection.
Following topical administration, CMS accumulated in the stratum corneum without penetration into deeper viable epidermal layers. The same was observed in atopic dermatitis mice, indicating that barrier alterations in atopic dermatitis had no influence on the penetration of CMS. Following subcutaneous injection, CMS were deposited in the regional lymph nodes as well as in liver, spleen, lung, and kidney. However, in vitro toxicity tests, clinical data, and morphometry-assisted histopathological analyses yielded no evidence of any toxic or otherwise adverse local or systemic effects of CMS, nor did they affect the severity or course of atopic dermatitis.
Taken together, CMS accumulate in the stratum corneum in both healthy and inflammatory skin and appear to be highly biocompatible in the mouse even under conditions of atopic dermatitis and thus could potentially serve to create a depot for anti-inflammatory drugs in the skin.
Cells and organelles are not homogeneous but include microcompartments that alter the spatiotemporal characteristics of cellular processes. The effects of microcompartmentation on metabolic pathways are however difficult to study experimentally. The pyrenoid is a microcompartment that is essential for a carbon concentrating mechanism (CCM) that improves the photosynthetic performance of eukaryotic algae. Using Chlamydomonas reinhardtii, we obtained experimental data on photosynthesis, metabolites, and proteins in CCM-induced and CCM-suppressed cells. We then employed a computational strategy to estimate how fluxes through the Calvin-Benson cycle are compartmented between the pyrenoid and the stroma. Our model predicts that ribulose-1,5-bisphosphate (RuBP), the substrate of Rubisco, and 3-phosphoglycerate (3PGA), its product, diffuse in and out of the pyrenoid, respectively, with higher fluxes in CCM-induced cells. It also indicates that there is no major diffusional barrier to metabolic flux between the pyrenoid and stroma. Our computational approach represents a stepping stone to understanding microcompartmentalized CCM in other organisms.
The Warm-Hot Intergalactic Medium (WHIM) arises from shock-heated gas collapsing in large-scale filaments and probably harbours a substantial fraction of the baryons in the local Universe. Absorption-line measurements in the ultraviolet (UV) and in the X-ray band currently represent the best method to study the WHIM at low redshifts. We here describe the physical properties of the WHIM and the concepts behind WHIM absorption line measurements of Hi and high ions such as Ovi, Ovii, and Oviii in the far-ultraviolet and X-ray band. We review results of recent WHIM absorption line studies carried out with UV and X-ray satellites such as FUSE, HST, Chandra, and XMM-Newton and discuss their implications for our knowledge of the WHIM.
Ecological and physiological factors lead to different contamination patterns in individual marine mammals. The objective of the present study was to assess whether variations in contamination profiles are indicative of social structures of young male sperm whales as they might reflect a variation in feeding preferences and/or in utilized feeding grounds. We used a total of 61 variables associated with organic compounds and trace element concentrations measured in muscle, liver, kidney and blubber gained from 24 sperm whales that stranded in the North Sea in January and February 2016. Combining contaminant and genetic data, there is evidence for at least two cohorts with different origin among these stranded sperm whales; one from the Canary Island region and one from the northern part of the Atlantic. While genetic data unravel relatedness and kinship, contamination data integrate over areas, where animals occured during their lifetime. Especially in long-lived animals with a large migratory potential, as sperm whales, contamination data may carry highly relevant information about aggregation through time and space.