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Typically, plastic packaging materials are produced using additives, like e.g. stabilisers, to introduce specific desired properties into the material or, in case of stabilisers, to prolong the shelf life of such packaging materials. However, those stabilisers are typically fossil-based and can pose risks to both environmental and human health. Therefore, the present study presents more sustainable alternatives based on regional renewable resources which show the relevant antioxidant, antimicrobial and UV absorbing properties to successfully serve as a plastic stabiliser. In the study, all plants are extracted and characterised with regard to not only antioxidant, antimicrobial and UV absorbing effects, but also with regard to additional relevant information like chemical constituents, molar mass distribution, absorbance in the visible range et cetera. The extraction process is furthermore optimised and, where applicable, reasonable opportunities for waste valorisation are explored and analysed. Furthermore, interactions between analysed plant extracts are described and model films based on Poly-Lactic Acid are prepared, incorporating analysed plant extracts. Based on those model films, formulation tests and migration analysis according to EU legislation is conducted.
The well-known aromatic and medicinal plant thyme (Thymus vulgaris L.) includes phenolic terpenoids like thymol and carvacrol which have strong antioxidant, antimicrobial and UV absorbing effects. Analyses show that those effects can be used in both lipophilic and hydrophilic surroundings, that the variant Varico 3 is a more potent cultivar than other analysed thyme variants, and that a passive extraction setup can be used for extract preparation while distillation of the Essential Oils can be a more efficient approach.
Macromolecular antioxidant polyphenols, particularly proanthocyanidins, have been found in the seed coats of the European horse chestnut (Aesculus hippocastanum L.) which are regularly discarded in phytopharmaceutical industry. In this study, such effects and compounds have been reported for the first time while a valorisation of waste materials has been analysed successfully. Furthermore, a passive extraction setup for waste materials and whole seeds has been developed. In extracts of snowdrops, precisely Galanthus elwesii HOOK.F., high concentrations of tocopherol have been found which promote a particularly high antioxidant capacity in lipophilic surroundings. Different coniferous woods (Abies div., Picea div.) which are in use as Christmas trees are extracted after separating the biomass in leafs and wood parts before being analysed regarding extraction optimisation and drought resistance of active substances. Antioxidant and UV absorbing proanthocyanidins are found even in dried biomasses, allowing the circular use of already used Christmas trees as bio-based stabilisers and the production of sustainable paper as a byproduct.
Sensoren können verschiedene Aufgaben erfüllen, wie beispielsweise die Optimierung von Prozessen, die Interaktion zwischen Geräten oder die Verbesserung der zivilen Sicherheit. [1–3] Ihr Bedarf für die Industrie oder den Alltag wächst seit Jahren stetig. Besonders mobile Gassensoren sind von großem Interesse. Jedoch ist ihre Anwendung meist durch ihre integrierte Batterie begrenzt. Gassensoren ohne oder mit einem nur sehr geringen Energieverbrauch stehen daher im Interesse bei neuen Anwendungsgebieten, beispielsweise im Brandschutz oder in der Textilindustrie. [4,5] Die Sensoren könnten zum Beispiel in die Textilien einer persönlichen Schutzausrüstung eingearbeitet werden und durch einen Farbumschlag die Anwesenheit eines Gases oder die Überschreitung des Grenzwertes toxischer Substanzen anzeigen.
Bonding wires made of aluminum are the most used materials for the transmission of electrical signals in power electronic devices. During operation, different cyclic mechanical and thermal stresses can lead to fatigue loads and a failure of the bonding wires. A prediction or prevention of the wire failure is not yet possible by design for all cases. The following work presents meaningful fatigue tests in small wire dimensions and investigates the influence of the R-ratio on the lifetime of two different aluminum wires with a diameter of 300 μm each. The experiments show very reproducible fatigue results with ductile failure behavior. The endurable stress amplitude decreases linearly with an increasing stress ratio, which can be displayed by a Smith diagram, even though the applied maximum stresses exceed the initial yield stresses determined by tensile tests. A scaling of the fatigue results by the tensile strength indicates that the fatigue level is significantly influenced by the strength of the material. Due to the very consistent findings, the development of a generalized fatigue model for predicting the lifetime of bonding wires with an arbitrary loading situation seems to be possible and will be further investigated.
When the Artemis missions launch, NASA's Orion spacecraft (and crew as of the Artemis II mission) will be exposed to the deep space radiation environment beyond the protection of Earth's magnetosphere. Hence, it is essential to characterize the effects of space radiation, microgravity, and the combination thereof on cells and organisms, i.e., to quantify any correlations between the deep space radiation environment, genetic variation, and induced genetic changes in cells. To address this, the Artemis I mission will include the Peristaltic Laboratory for Automated Science with Multigenerations (PLASM) hardware containing the Deep Space Radiation Genomics (DSRG) experiment. The scientific aims of DSRG are (i) to identify the metabolic and genomic pathways in yeast affected by microgravity, space radiation, and their combination, and (ii) to differentiate between gravity and radiation exposure on single-gene deletion/overexpressing strains' ability to thrive in the spaceflight environment. Yeast is used as a model system because 70% of its essential genes have a human homolog, and over half of these homologs can functionally replace their human counterpart. As part of the experiment preparation towards spaceflight, an Experiment Verification Test (EVT) was performed at the Kennedy Space Center to verify that the experiment design, hardware, and approach to automated operations will enable achieving the scientific aims. For the EVT, fluidic systems were assembled, sterilized, loaded, and acceptance-tested, and subsequently integrated with the engineering parts to produce a flight-like PLASM unit. Each fluidic system consisted of (i) a Media Bag, (ii) four Culture Bags loaded with Saccharomyces cerevisiae (two with deletion series and the remaining two with overexpression series), and (iii) tubing and check valves. The EVT PLASM unit was put under a temperature profile replicating the anticipated different phases of flight, including handover to launch, spaceflight, and splashdown to handover back to the science team, for a 58-day period. At EVT completion, the rate of activation, cellular growth, RNA integrity, and sample contamination were interrogated. All of the experiment's success criteria were satisfied, encouraging our efforts to perform this investigation on Artemis I. This manuscript thus describes the process of spaceflight experiment design maturation with a focus on the EVT, its results, DSRG's preparation for its planned launch on Artemis I in 2022, and how the PLASM hardware can enable other scientific goals on future Artemis missions and/or the Lunar Orbital Platform – Gateway.
Hydrophilic surface-enhanced Raman spectroscopy (SERS) substrates were prepared by a combination of TiO2-coatings of aluminium plates through a direct titanium tetraisopropoxide (TTIP) coating and drop coated by synthesised gold nanoparticles (AuNPs). Differences between the wettability of the untreated substrates, the slowly dried Ti(OH)4 substrates and calcinated as well as plasma treated TiO2 substrates were analysed by water contact angle (WCA) measurements. The hydrophilic behaviour of the developed substrates helped to improve the distribution of the AuNPs, which reflects in overall higher lateral SERS enhancement. Surface enhancement of the substrates was tested with target molecule rhodamine 6G (R6G) and a fibre-coupled 638 nm Raman spectrometer. Additionally, the morphology of the substrates was characterised using scanning electron microscopy (SEM) and Raman microscopy. The studies showed a reduced influence of the coffee ring effect on the particle distribution, resulting in a more broadly distributed edge region, which increased the spatial reproducibility of the measured SERS signal in the surface-enhanced Raman mapping measurements on mm scale.
A main factor hampering life in space is represented by high atomic number nuclei and energy (HZE) ions that constitute about 1% of the galactic cosmic rays. In the frame of the “STARLIFE” project, we accessed the Heavy Ion Medical Accelerator (HIMAC) facility of the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. By means of this facility, the extremophilic species Haloterrigena hispanica and Parageobacillus thermantarcticus were irradiated with high LET ions (i.e., Fe, Ar, and He ions) at doses corresponding to long permanence in the space environment. The survivability of HZE-treated cells depended upon either the storage time and the hydration state during irradiation; indeed, dry samples were shown to be more resistant than hydrated ones. With particular regard to spores of the species P. thermantarcticus, they were the most resistant to irradiation in a water medium: an analysis of the changes in their biochemical fingerprinting during irradiation showed that, below the survivability threshold, the spores undergo to a germination-like process, while for higher doses, inactivation takes place as a consequence of the concomitant release of the core’s content and a loss of integrity of the main cellular components. Overall, the results reported here suggest that the selected extremophilic microorganisms could serve as biological model for space simulation and/or real space condition exposure, since they showed good resistance to ionizing radiation exposure and were able to resume cellular growth after long-term storage.
(1) Background: Autologous bone is supposed to contain vital cells that might improve the osseointegration of dental implants. The aim of this study was to investigate particulate and filtered bone chips collected during oral surgery intervention with respect to their osteogenic potential and the extent of microbial contamination to evaluate its usefulness for jawbone reconstruction prior to implant placement. (2) Methods: Cortical and cortical-cancellous bone chip samples of 84 patients were collected. The stem cell character of outgrowing cells was characterized by expression of CD73, CD90 and CD105, followed by osteogenic differentiation. The degree of bacterial contamination was determined by Gram staining, catalase and oxidase tests and tests to evaluate the genera of the found bacteria (3) Results: Pre-surgical antibiotic treatment of the patients significantly increased viability of the collected bone chip cells. No significant difference in plasticity was observed between cells isolated from the cortical and cortical-cancellous bone chip samples. Thus, both types of bone tissue can be used for jawbone reconstruction. The osteogenic differentiation was independent of the quantity and quality of the detected microorganisms, which comprise the most common bacteria in the oral cavity. (4) Discussion: This study shows that the quality of bone chip-derived stem cells is independent of the donor site and the extent of present common microorganisms, highlighting autologous bone tissue, assessable without additional surgical intervention for the patient, as a useful material for dental implantology.
Hydrogen‐Bonded Cholesteric Liquid Crystals—A Modular Approach Toward Responsive Photonic Materials
(2022)
A supramolecular approach for photonic materials based on hydrogen-bonded cholesteric liquid crystals is presented. The modular toolbox of low-molecular-weight hydrogen-bond donors and acceptors provides a simple route toward liquid crystalline materials with tailor-made thermal and photonic properties. Initial studies reveal broad application potential of the liquid crystalline thin films for chemo- and thermosensing. The chemosensing performance is based on the interruption of the intermolecular forces between the donor and acceptor moieties by interference with halogen-bond donors. Future studies will expand the scope of analytes and sensing in aqueous media. In addition, the implementation of the reported materials in additive manufacturing and printed photonic devices is planned.
A precise characterization of substances is essential for the safe handling of explosives. One parameter regularly characterized is the impact sensitivity. This is typically determined using a drop hammer. However, the results can vary depending on the test method and even the operator, and it is not possible to distinguish the type of decomposition such as detonation and deflagration. This study monitors the reaction progress by constructing a drop hammer to measure the decomposition reaction of four different primary explosives (tetrazene, silver azide, lead azide, lead styphnate) in order to determine the reproducibility of this method. Additionally, further possible evaluation methods are explored to improve on the current binary statistical analysis. To determine whether classification was possible based on extracted features, the responses of equipped sensor arrays, which measure and monitor the reactions, were studied and evaluated. Features were extracted from this data and were evaluated using multivariate methods such as principal component analysis (PCA) and linear discriminant analysis (LDA). The results indicate that although the measurements show substance specific trends, they also show a large scatter for each substance. By reducing the dimensions of the extracted features, different sample clusters can be represented and the calculated loadings allow significant parameters to be determined for classification. The results also suggest that differentiation of different reaction mechanisms is feasible. Testing of the regressor function shows reliable results considering the comparatively small amount of data.
The following work presents algorithms for semi-automatic validation, feature extraction and ranking of time series measurements acquired from MOX gas sensors. Semi-automatic measurement validation is accomplished by extending established curve similarity algorithms with a slope-based signature calculation. Furthermore, a feature-based ranking metric is introduced. It allows for individual prioritization of each feature and can be used to find the best performing sensors regarding multiple research questions. Finally, the functionality of the algorithms, as well as the developed software suite, are demonstrated with an exemplary scenario, illustrating how to find the most power-efficient MOX gas sensor in a data set collected during an extensive screening consisting of 16,320 measurements, all taken with different sensors at various temperatures and analytes.
With the increasing demand for ultrapure water in the pharmaceutical and semiconductor industry, the need for precise measuring instruments for those applications is also growing. One critical parameter of water quality is the amount of total organic carbon (TOC). This work presents a system that uses the advantage of the increased oxidation power achieved with UV/O3 advanced oxidation process (AOP) for TOC measurement in combination with a significant miniaturization compared to the state of the art. The miniaturization is achieved by using polymer-electrolyte membrane (PEM) electrolysis cells for ozone generation in combination with UV-LEDs for irradiation of the measuring solution, as both components are significantly smaller than standard equipment. Conductivity measurement after oxidation is the measuring principle and measurements were carried out in the TOC range between 10 and 1000 ppb TOC. The suitability of the system for TOC measurement is demonstrated using the oxidation by ozonation combined with UV irradiation of defined concentrations of isopropyl alcohol (IPA).
Simultaneous determination of selected catechins and pyrogallol in deer intoxications by HPLC-MS/MS
(2021)
Aim: To understand how transcriptional factors Pdr1 and Pdr3, belonging to the pleiotropic drug resistance system, are activated, and regulated after introducing chemical toxins to the cell in the model organism Saccharomyces cerevisiae.
Methods: Series of molecular methods were applied using different strains of S. cerevisiae over-expressing proteins of interest as a eukaryotic cell model. The chemical stress introduced to the cell is represented by menadione. Results were obtained performing protein detection and analysis. Additionally, the regulation of the DNA binding of the transcriptional activators after stimulation is quantified using chromatin immunoprecipitation, employing epitope-tagged factors and real-time qPCR.
Results: Our results indicated higher expression levels of the Pdr1 transcriptional factor, compared to its homologous Pdr3 after treatment with menadione. The yeast-cell defence system was tested against various organic solvents to exclude the possibility of their presence potentially affecting the results. The results indicate that Pdr1 is most abundant after 30 minutes from the beginning of the treatment, compared with 240 minutes after the treatment when the function of the transcription factor is faded. It appears that Pdr1 binding to the PDR5 and SNQ2 promoters, which are both activated by Pdr1, peaks around the same time, or more precisely after 40 minutes from the start of the treatment.
Conclusion: The tendency of Pdr1 reduction after its activation by menadione is detected. One possibility is that Pdr1, after recognizing the xenobiotic menadione, is removed by a degradation mechanism. Given the fact that Pdr1 directly binds the xenobiotic molecule, its destruction might help the cells to remove toxic levels of menadione. It is possible that overexpressing the part of Pdr1 which recognizes menadione alone was sufficient to detoxify and hence produce a tolerance towards menadione.
Our study shows ZP2 to be a new biomarker for diagnosis, best used in combination with other low abundant genes in colon cancer. Furthermore, ZP2 promotes cell proliferation via the ERK1/2-cyclinD1-signaling pathway. We demonstrate that ZP2 mRNA is expressed in a low-abundant manner with high specificity in subsets of cancer cell lines representing different cancer subtypes and also in a significant proportion of primary colon cancers. The potential benefit of ZP2 as a biomarker is discussed. In the second part of our study, the function of ZP2 in cancerogenesis has been analyzed. Since ZP2 shows an enhanced transcript level in colon cancer cells, siRNA experiments have been performed to verify the potential role of ZP2 in cell proliferation. Based on these data, ZP2 might serve as a new target molecule for cancer diagnosis and treatment in respective cancer types such as colon cancer.
In thyroid carcinoma cells, the soluble βgalactosidespecific lectin, galectin3, is extra and intracellularly expressed and plays a significant role in thyroid cancer diagnosis. The functional relevance of this molecule, particularly in its extracellular environment however, warrants further elucidation. To gain insight into this topic, the present study characterized principal functional properties of galectin3 in 3 commonly used thyroid carcinoma cell lines (BCPAP, Cal62 and FTC133) that express the molecule intra and extracellulary. Cellintrinsic galectin3 harbors a functional carbohydrate recognition domain as determined by affinity purification. Moreover, cell surface expressed galectin3 can be partially removed by treatment with lactose or asialofetuin, but not with sucrose. Thyroid carcinoma cells adhere to substratebound galectin3 in a βgalactosidespecific manner, whereby only cell adhesion, but not cell migration is promoted. Thus, thyroid tumor cells harbor functional active galectin3 that, inter alia, specifically interacts with cell surfaceexpressed molecular ligands in a βgalactosidedependent manner, whereby the molecule can at least interfere with cell adhesion. The modulation of galectin3 expression level or its ligands in such tumor cells could be of therapeutic interest and needs further experimental clarification.
Background: Staurosporine-dependent single and collective cell migration patterns of breast carcinoma cells MDA-MB-231, MCF-7, and SK-BR-3 were analysed to characterise the presence of drug-dependent migration promoting and inhibiting yin-yang effects. Methods: Migration patterns of various breast cancer cells after staurosporine treatment were investigated using Western blot, cell toxicity assays, single and collective cell migration assays, and video time-lapse. Statistical analyses were performed with Kruskal–Wallis and Fligner–Killeen tests. Results: Application of staurosporine induced the migration of single MCF-7 cells but inhibited collective cell migration. With the exception of low-density SK-BR-3 cells, staurosporine induced the generation of immobile flattened giant cells. Video time-lapse analysis revealed that within the borderline of cell collectives, staurosporine reduced the velocity of individual MDA-MB-231 and SK-BR-3, but not of MCF-7 cells. In individual MCF-7 cells, mainly the directionality of migration became disturbed, which led to an increased migration rate parallel to the borderline, and hereby to an inhibition of the migration of the cell collective as a total. Moreover, the application of staurosporine led to a transient activation of ERK1/2 in all cell lines. Conclusion: Dependent on the context (single versus collective cells), a drug may induce opposite effects in the same cell line.
The solvent exchange as one of the most important steps during the manufacturing process of organic aerogels was investigated. This step is crucial as a preparatory step for the supercritical drying, since the pore solvent must be soluble in supercritical carbon dioxide to enable solvent extraction. The development and subsequent optimization of a suitable system with a peristaltic pump for automatic solvent exchange proved to be a suitable approach. In addition, the influence of zeolites on the acceleration of the process was found to be beneficial. To investigate the process, the water content in acetone was determined at different times using Karl Fischer titration. The shrinkage, densities, as well as the surface areas of the aerogels were analyzed. Based on these, the influence of various process parameters on the final structure of the obtained aerogels was investigated and evaluated. Modeling on diffusion in porous materials completes this study.
Here we provide the electrophysiology data for the manuscript "Two functional epithelial sodium channel isoforms are present in rodents despite pronounced evolutionary pseudogenization and exon fusion", published in Molecular Biology and Evolution (2021): msab271 (doi: 10.1093/molbev/msab271). Data are reported as current values in Excel format, sorted according to the appearance in Figures and supplemented by explanatory text on the procedures/data presentation.
The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Fabry disease (FD) is an X‐linked lysosomal storage disorder. Deficiency of the lysosomal enzyme alpha‐galactosidase (GLA) leads to accumulation of potentially toxic globotriaosylceramide (Gb3) on a multisystem level. Cardiac and cerebrovascular abnormalities as well as progressive renal failure are severe, life‐threatening long‐term complications. The complete pathophysiology of chronic kidney disease (CKD) in FD and the role of tubular involvement for its progression are unclear.
We established human renal tubular epithelial cell lines from the urine of male FD patients and male controls. The renal tubular system is rich in mitochondria and involved in transport processes at high energy costs. Our studies revealed fragmented mitochondria with disrupted cristae structure in FD patient cells. Oxidative stress levels were elevated and oxidative phosphorylation was up‐regulated in FD pointing at enhanced energetic needs. Mitochondrial homeostasis and energy metabolism revealed major changes as evidenced by differences in mitochondrial number, energy production and fuel consumption. The changes were accompanied by activation of the autophagy machinery in FD. Sirtuin1, an important sensor of (renal) metabolic stress and modifier of different defense pathways, was highly expressed in FD.
Our data show that lysosomal FD impairs mitochondrial function and results in severe disturbance of mitochondrial energy metabolism in renal cells. This insight on a tissue‐specific level points to new therapeutic targets which might enhance treatment efficacy.
3-Hydroxyisobutyrate Dehydrogenase (HIBADH) deficiency - a novel disorder of valine metabolism
(2021)
3-Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched-chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3-hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low-valine diet. The detected mutation in the HIBADH gene leads to nonsense-mediated mRNA decay of the mutant allele and to a complete loss-of-function of the enzyme. Under strict adherence to a low-valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.
Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re‐evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well‐informed decisions in the context of MMA and PA patient care.
The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.
Cysticfibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressiveand life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe theclinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individu-als harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made inprimary human bronchial epithelial cultures (HBEs) andXenopusoocytes. Molecular properties of R751L-CFTR were investigatedin the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotypeassociated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and asso-ciated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function inXenopusoocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall,R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR.This is thefirst report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological proper-ties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly,inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to al-ternative non-CFTR factors, which require further investigation.
Background: Atypical myopathy (AM), an acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in horses, induce changes in mitochondrial metabolism. Only few veterinary laboratories offer diagnostic testing for this disease. Inborn and acquired MADD exist in humans, therefore determination of organic acids (OA) in urine and acylcarnitines (AC) in blood by assays available in medical laboratories can serve as AM diagnostics. The evolution of OA and AC profiles in surviving horses is unreported.
Methods: AC profiles using electrospray ionization tandem mass spectrometry (ESI-MS/MS) and OA in urine using gas chromatography mass spectrometry (GC–MS) were determined in dried blot spots (DBS, n = 7) and urine samples (n = 5) of horses with AM (n = 7) at disease presentation and in longitudinal samples from 3/4 survivors and compared to DBS (n = 16) and urine samples (n = 7) from control horses using the Wilcoxon test.
Results: All short- (C2-C5) and medium-chain (C6-C12) AC in blood differed significantly (p < 0.008) between horses with AM and controls, except for C5:1 (p = 0.45) and C5OH + C4DC (p = 0.06). In AM survivors the AC concentrations decreased over time but were still partially elevated after 7 days. 14/62 (23%) of OA differed significantly between horses with AM and control horses. Concentrations of ethylmalonic acid, 2-hydroxyglutaric acid and the acylglycines (butyryl-, valeryl-, and hexanoylglycine) were highly elevated in the urine of all horses with AM at the day of disease presentation. In AM survivors, concentrations of those metabolites were initially lower and decreased during remission to approach normalization after 7 days.
Conclusion: OA and AC profiling by specialized human medical laboratories was used to diagnose AM in horses. Elevation of specific metabolites were still evident several days after disease presentation, allowing diagnosis via analysis of samples from convalescent animals.
The epithelial sodium channel (ENaC) plays a key role in salt and water homeostasis in tetrapod vertebrates. There are four ENaC subunits (α, β, γ, δ), forming heterotrimeric αβγ- or δβγ-ENaCs. While the physiology of αβγ-ENaC is well understood, for decades the field has stalled with respect to δβγ-ENaC due to the lack of mammalian model organisms. The SCNN1D gene coding for δ-ENaC was previously believed to be absent in rodents, hindering studies using standard laboratory animals. We analysed all currently available rodent genomes and discovered that SCNN1D is present in rodents but was independently lost in five rodent lineages, including the Muridae (mice and rats). The independent loss of SCNN1D in rodent lineages may be constrained by phylogeny and taxon-specific adaptation to dry habitats, however habitat aridity does not provide a selection pressure for maintenance of SCNN1D across Rodentia. A fusion of two exons coding for a structurally flexible region in the extracellular domain of δ-ENaC appeared in the Hystricognathi (a group that includes guinea pigs). This conserved pattern evolved at least 41 Ma ago and represents a new autapomorphic feature for this clade. Exon fusion does not impair functionality of guinea pig (Cavia porcellus) δβγ-ENaC expressed in Xenopus oocytes. Electrophysiological characterisation at the whole-cell and single-channel level revealed conserved biophysical features and mechanisms controlling guinea pig αβγ- and δβγ-ENaC function as compared to human orthologues. Guinea pigs therefore represent commercially available mammalian model animals that will help shed light on the physiological function of δ-ENaC.
The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium ratio ∼10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). This discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs, and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we used conventional and noncanonical amino acid-based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that these regions contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work suggests that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. These results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels.
This study investigates the effects of four multifunctional chain-extending cross-linkers (CECL) on the processability, mechanical performance, and structure of polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) blends produced using film blowing technology. The newly developed reference compound (M·VERA® B5029) and the CECL modified blends are characterized with respect to the initial properties and the corresponding properties after aging at 50 °C for 1 and 2 months. The tensile strength, seal strength, and melt volume rate (MVR) are markedly changed after thermal aging, whereas the storage modulus, elongation at the break, and tear resistance remain constant. The degradation of the polymer chains and crosslinking with increased and decreased MVR, respectively, is examined thoroughly with differential scanning calorimetry (DSC), with the results indicating that the CECL-modified blends do not generally endure thermo-oxidation over time. Further, DSC measurements of 25 µm and 100 µm films reveal that film blowing pronouncedly changes the structures of the compounds. These findings are also confirmed by dynamic mechanical analysis, with the conclusion that tris(2,4-di-tert-butylphenyl)phosphite barely affects the glass transition temperature, while with the other changes in CECL are seen. Cross-linking is found for aromatic polycarbodiimide and poly(4,4-dicyclohexylmethanecarbodiimide) CECL after melting of granules and films, although overall the most synergetic effect of the CECL is shown by 1,3-phenylenebisoxazoline.
Cytokine-induced killer (CIK) cells are an ex vivo expanded heterogeneous cell population with an enriched NK-T phenotype (CD3+CD56+). Due to the convenient and relatively inexpensive expansion capability, together with low incidence of graft versus host disease (GVHD) in allogeneic cancer patients, CIK cells are a promising candidate for immunotherapy. It is well known that natural killer group 2D (NKG2D) plays an important role in CIK cell-mediated antitumor activity; however, it remains unclear whether its engagement alone is sufficient or if it requires additional co-stimulatory signals to activate the CIK cells. Likewise, the role of 2B4 has not yet been identified in CIK cells. Herein, we investigated the individual and cumulative contribution of NKG2D and 2B4 in the activation of CIK cells. Our analysis suggests that (a) NKG2D (not 2B4) is implicated in CIK cell (especially CD3+CD56+ subset)-mediated cytotoxicity, IFN-γ secretion, E/T conjugate formation, and degranulation; (b) NKG2D alone is adequate enough to induce degranulation, IFN-γ secretion, and LFA-1 activation in CIK cells, while 2B4 only provides limited synergy with NKG2D (e.g., in LFA-1 activation); and (c) NKG2D was unable to costimulate CD3. Collectively, we conclude that NKG2D engagement alone suffices to activate CIK cells, thereby strengthening the idea that targeting the NKG2D axis is a promising approach to improve CIK cell therapy for cancer patients. Furthermore, CIK cells exhibit similarities to classical invariant natural killer (iNKT) cells with deficiencies in 2B4 stimulation and in the costimulation of CD3 with NKG2D. In addition, based on the current data, the divergence in receptor function between CIK cells and NK (or T) cells can be assumed, pointing to the possibility that molecular modifications (e.g., using chimeric antigen receptor technology) on CIK cells may need to be customized and optimized to maximize their functional potential.
Because the robust and rapid determination of spoilage microorganisms is becoming increasingly important in industry, the use of IR microspectroscopy, and the establishment of robust and versatile chemometric models for data processing and classification, is gaining importance. To further improve the chemometric models, bacterial stress responses were induced, to study the effect on the IR spectra and to improve the chemometric model. Thus, in this work, nine important food-relevant microorganisms were subjected to eight stress conditions, besides the regular culturing as a reference. Spectral changes compared to normal growth conditions without stressors were found in the spectral regions of 900–1500 cm−1 and 1500–1700 cm−1. These differences might stem from changes in the protein secondary structure, exopolymer production, and concentration of nucleic acids, lipids, and polysaccharides. As a result, a model for the discrimination of the studied microorganisms at the genus, species and strain level was established, with an accuracy of 96.6%. This was achieved despite the inclusion of various stress conditions and times after incubation of the bacteria. In addition, a model was developed for each individual microorganism, to separate each stress condition or regular treatment with 100% accuracy.
The ability to discriminate between different ionic species, termed ion selectivity, is a key feature of ion channels and forms the basis for their physiological function. Members of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily of trimeric ion channels are typically sodium selective, but to a surprisingly variable degree. While acid-sensing ion channels (ASICs) are weakly sodium selective (sodium:potassium around 10:1), ENaCs show a remarkably high preference for sodium over potassium (>500:1). The most obvious explanation for this discrepancy may be expected to originate from differences in the pore-lining second transmembrane segment (M2). However, these show a relatively high degree of sequence conservation between ASICs and ENaCs and previous functional and structural studies could not unequivocally establish that differences in M2 alone can account for the disparate degrees of ion selectivity. By contrast, surprisingly little is known about the contributions of the first transmembrane segment (M1) and the preceding pre-M1 region. In this study, we use conventional and non-canonical amino acid-based mutagenesis in combination with a variety of electrophysiological approaches to show that the pre-M1 and M1 regions of mASIC1a channels are major determinants of ion selectivity. Mutational investigations of the corresponding regions in hENaC show that they contribute less to ion selectivity, despite affecting ion conductance. In conclusion, our work supports the notion that the remarkably different degrees of sodium selectivity in ASICs and ENaCs are achieved through different mechanisms. The results further highlight how M1 and pre-M1 are likely to differentially affect pore structure in these related channels.
Ausführungsbeispiele schaffen eine Vorrichtung zur Desinfektion oder Sanitisierung zumindest eines Gegenstands. Die Vorrichtung umfasst einen Ozongenerator, der ausgebildet ist, um Ozon zu erzeugen und in einem Volumen freizusetzen. Ferner umfasst die Vorrichtung einen Ozonsensor, der ausgebildet ist, um eine Ozonkonzentration in dem Volumen zu messen. Ferner umfasst die Vorrichtung eine Steuereinrichtung, die konfiguriert ist, um den Ozongenerator anzusteuern Ozon zu erzeugen, so dass eine gemessene Ozonkonzentration für einen vorgegebenen Zeitraum bei einer vorgegebenen Ozonkonzentration oder innerhalb eines vorgegebenen Ozonkonzentrationsbereichs liegt, um in dem Volumen befindliche Gegenstände zu desinfizieren oder sanitisieren.
The molecular weight properties of lignins are one of the key elements that need to be analyzed for a successful industrial application of these promising biopolymers. In this study, the use of 1H NMR as well as diffusion-ordered spectroscopy (DOSY NMR), combined with multivariate regression methods, was investigated for the determination of the molecular weight (Mw and Mn) and the polydispersity of organosolv lignins (n = 53, Miscanthus x giganteus, Paulownia tomentosa, and Silphium perfoliatum). The suitability of the models was demonstrated by cross validation (CV) as well as by an independent validation set of samples from different biomass origins (beech wood and wheat straw). CV errors of ca. 7–9 and 14–16% were achieved for all parameters with the models from the 1H NMR spectra and the DOSY NMR data, respectively. The prediction errors for the validation samples were in a similar range for the partial least squares model from the 1H NMR data and for a multiple linear regression using the DOSY NMR data. The results indicate the usefulness of NMR measurements combined with multivariate regression methods as a potential alternative to more time-consuming methods such as gel permeation chromatography.
The synthesis and characterization of a new class of 1,2,4-oxadiazolylpyridinium as a cationic scaffold for fluorinated ionic liquid crystals is herein described. A series of 12 fluorinated heterocyclic salts based on a 1,2,4-oxadiazole moiety, connected through its C(5) or C(3) to an N-alkylpyridinium unit and a perfluoroheptyl chain, differing in the length of the alkyl chain and counterions, has been synthesized. As counterions iodide, bromide and bis(trifluoromethane)sulfonimide have been considered. The synthesis, structure, and liquid crystalline properties of these compounds are discussed on the basis of the tuned structural variables. The thermotropic properties of this series of salts have been investigated by differential scanning calorimetry and polarized optical microscopy. The results showed the existence of an enantiotropic mesomorphic smectic liquid crystalline phase for six bis(trifluoromethane)sulfonimide salts.
As a low-input crop, Miscanthus offers numerous advantages that, in addition to agricultural applications, permits its exploitation for energy, fuel, and material production. Depending on the Miscanthus genotype, season, and harvest time as well as plant component (leaf versus stem), correlations between structure and properties of the corresponding isolated lignins differ. Here, a comparative study is presented between lignins isolated from M. x giganteus, M. sinensis, M. robustus and M. nagara using a catalyst-free organosolv pulping process. The lignins from different plant constituents are also compared regarding their similarities and differences regarding monolignol ratio and important linkages. Results showed that the plant genotype has the weakest influence on monolignol content and interunit linkages. In contrast, structural differences are more significant among lignins of different harvest time and/or season. Analyses were performed using fast and simple methods such as nuclear magnetic resonance (NMR) spectroscopy. Data was assigned to four different linkages (A: β-O-4 linkage, B: phenylcoumaran, C: resinol, D: β-unsaturated ester). In conclusion, A content is particularly high in leaf-derived lignins at just under 70% and significantly lower in stem and mixture lignins at around 60% and almost 65%. The second most common linkage pattern is D in all isolated lignins, the proportion of which is also strongly dependent on the crop portion. Both stem and mixture lignins, have a relatively high share of approximately 20% or more (maximum is M. sinensis Sin2 with over 30%). In the leaf-derived lignins, the proportions are significantly lower on average. Stem samples should be chosen if the highest possible lignin content is desired, specifically from the M. x giganteus genotype, which revealed lignin contents up to 27%. Due to the better frost resistance and higher stem stability, M. nagara offers some advantages compared to M. x giganteus. Miscanthus crops are shown to be very attractive lignocellulose feedstock (LCF) for second generation biorefineries and lignin generation in Europe.
New sustainable, environmentally friendly materials for thermal insulation of buildings are necessary to reduce their carbon footprints. In this study, Miscanthus fiber-reinforced geopolymer composites, foamed with sodium dodecyl sulfate (SDS), were developed using fly ash as a geopolymer precursor. The effects of fiber content, fiber size, curing temperature, foaming agent content, fumed silica specific surface area and fumed silica content on thermal conductivity and compressive strength were evaluated using a Plackett-Burman design of experiment. Furthermore, the microstructure of geopolymer composites was investigated using X-ray diffraction (XRD), X-ray micro-computed tomography (μCT) and scanning electron microscopy (SEM). The measured characteristic values were in the following ranges: Thermal conductivity 0.057 W (m K)−1 to 0.127 W (m K)−1, compressive strength 0.007 MPa–0.719 MPa and porosity 49 vol% to 76 vol%. The results reveal an enhancement of thermal conductivity by elevated fiber size and foaming agent content. In contrast, the compressive strength is enhanced by high fiber content. Additionally, SEM images indicate a good interaction between the fibers and the geopolymer matrix, because nearly the whole fiber surface is covered by the geopolymer.
Isolation of DNA and RNA
(2021)
Polymerase Chain Reaction
(2021)
Intimate swabs taken for examination in sexual assault cases typically yield mixtures of sperm and epithelial cell types. While powerful, differential extraction protocols to overcome such cell type mixtures by separate lysis of epithelial cells and spermatozoa can still prove ineffective, in particular if only few sperm cells are present or if swabs contain sperm from more than one individual leading to complex low level DNA mixtures. A means to avoid such mixtures consists in the analysis of single micromanipulated sperm cells. However, the quantity of DNA from single sperm cells is not sufficient for conventional STR analysis. Here, we describe a simple method for micromanipulating individual sperm cells from intimate swabs and show that whole genome amplification can generate sufficient amounts of DNA from single cells for subsequent DNA profiling. We recovered over 80% of alleles of haploid autosomal STR profiles from the majority of individual sperm cells. Furthermore, we demonstrate that in mixtures of sperm from two contributors, Y-STR and X-STR profiles of individual sperm cells can be used to sort the haploid autosomal profiles to develop the diploid consensus STR profiles of the individual donors. Finally, by analysing single sperm cells from mock sexual assault swabs with one or two sperm donors, we showed that our protocols enabled the identification of the unknown male contributors.
The analysis of used engine oils from industrial engines enables the study of engine wear and oil degradation in order to evaluate the necessity of oil changes. As the matrix composition of an engine oil strongly depends on its intended application, meaningful diagnostic oil analyses bear considerable challenges. Owing to the broad spectrum of available oil matrices, we have evaluated the applicability of using an internal standard and/or preceding sample digestion for elemental analysis of used engine oils via inductively coupled plasma optical emission spectroscopy (ICP OES). Elements originating from both wear particles and additives as well as particle size influence could be clearly recognized by their distinct digestion behaviour. While a precise determination of most wear elements can be achieved in oily matrix, the measurement of additives is performed preferably after sample digestion. Considering a dataset of physicochemical parameters and elemental composition for several hundred used engine oils, we have further investigated the feasibility of predicting the identity and overall condition of an unknown combustion engine using the machine learning system XGBoost. A maximum accuracy of 89.6% in predicting the engine type was achieved, a mean error of less than 10% of the observed timeframe in predicting the oil running time and even less than 4% for the total engine running time, based purely on common oil check data. Furthermore, obstacles and possibilities to improve the performance of the machine learning models were analysed and the factors that enabled the prediction were explored with SHapley Additive exPlanation (SHAP). Our results demonstrate that both the identification of an unknown engine as well as a lifetime assessment can be performed for a first estimation of the actual sample without requiring meticulous documentation.
Das Projekt adressiert ein Problem aus dem Bereich Medizintechnologie (ein NRW-Förderschwerpunkt): die Entwicklung eines für Patienten maßgeschneiderten Gewebeersatzmaterials, ein Knochensurrogat. Kritische (“critical size“) Knochendefekte stellen ein signifikantes Gesundheitsproblem dar, das durch die zurzeit gängigen Knochenersatzmaterialien nicht bzw. nicht effizient therapiert werden kann. Kritische Knochendefekte werden mit artifiziellen Biomaterialien behandelt, die bislang eine unzureichende Regenerationskapazität aufweisen.
The promotion of sustainable packaging is part of the European Green Deal and plays a key role in the EU’s social and political strategy. One option is the use of renewable resources and biomass waste as raw materials for polymer production. Lignocellulose biomass from annual and perennial industrial crops and agricultural residues are a major source of polysaccharides, proteins, and lignin, and can also be used to obtain plant-based extracts and essential oils. Therefore, these biomasses are considered as potential substitute for fossil-based resources. Here, the status quo of bio-based polymers is discussed and evaluated in terms of properties related to packaging applications such as gas and water vapor permeability as well as mechanical properties. So far, their practical use is still restricted due to lower performance in fundamental packaging functions that directly influence food quality and safety, the length of shelf life and thus the amount of food waste. Besides bio-based polymers, this review focuses on plant extracts as active packaging agents. Incorporating extracts of herbs, flowers, trees, and their fruits is inevitable to achieve desired material properties that are capable to prolong the food shelf life. Finally, the adoption potential of packaging based on polymers from renewable resources is discussed from a bioeconomy perspective.
DNA Sequencing
(2021)
A series of reactive binaphthyl‐diimine‐based dopants is prepared and investigated with respect to their potential for the chiral induction of structural coloration in nematic liquid crystal mixture E7 and the selective photonic sensing of nitrogen dioxide (NO2). Studies of the helical twisting power (HTP) in 4‐cyano‐4′‐pentylbiphenyl (5CB) reveal HTP values as high as 375 µm‐1 and the tremendous impact of structural compatibility and changes of the dihedral binaphthyl angle on the efficiency of the chiral transfer. Detailed investigation of the sensing capabilities of the systems reveals an extraordinarily high selectivity for NO2 and a response to concentrations as low as 100 ppm. The systems show a direct response to the analyte gas leading to a concentration‐dependent shift of the reflectance wavelength of up to several hundred nanometers. Incorporation of copper ions remarkably improves the sensor's properties in terms of sensitivity and selectivity, enabling the tailored tweaking of the system's properties.
The promotion of sustainable packaging is part of the European Green Deal and plays a key role in the EU’s social and political strategy. One option is the use of renewable resources and biomass waste as raw materials for polymer production. Lignocellulose biomass from annual and perennial industrial crops and agricultural residues are a major source of polysaccharides, proteins, and lignin and can also be used to obtain plant-based extracts and essential oils. Therefore, these biomasses are considered as potential substitute for fossil-based resources. Here, the status quo of bio-based polymers is discussed and evaluated in terms of properties related to packaging applications such as gas and water vapor permeability as well as mechanical properties. So far, their practical use is still restricted due to lower performance in fundamental packaging functions that directly influence food quality and safety, the length of shelf life, and thus the amount of food waste. Besides bio-based polymers, this review focuses on plant extracts as active packaging agents. Incorporating extracts of herbs, flowers, trees, and their fruits is inevitable to achieve desired material properties that are capable to prolong the food shelf life. Finally, the adoption potential of packaging based on polymers from renewable resources is discussed from a bioeconomy perspective.
The modern concept of the evolution of Mars assumes that life could potentially have originated on the planet Mars, possibly during the end of the late heavy bombardment, and could then be transferred to other planets. Since then, physical and chemical conditions on Mars changed and now strongly limit the presence of terrestrial-like life forms. These adverse conditions include scarcity of liquid water (although brine solutions may exist), low temperature and atmospheric pressure, and cosmic radiation. Ionizing radiation is very important among these life-constraining factors because it damages DNA and other cellular components, particularly in liquid conditions where radiation-induced reactive oxidants diffuse freely. Here, we investigated the impact of high doses (up to 2 kGy) of densely-ionizing (197.6 keV/µm), space-relevant iron ions (corresponding on the irradiation that reach the uppermost layer of the Mars subsurface) on the survival of an extremophilic terrestrial organism-Cryomyces antarcticus-in liquid medium and under atmospheric conditions, through different techniques. Results showed that it survived in a metabolically active state when subjected to high doses of Fe ions and was able to repair eventual DNA damages. It implies that some terrestrial life forms can withstand prolonged exposure to space-relevant ion radiation.
Different analyses and feasibility studies have been conducted on the plant extracts of thyme (Thymus vulgaris), European horse chestnut (Aesculus hippocastanum), Nordmann fir (Abies nordmanniana), and snowdrop (Galanthus elwesii) to evaluate bio‐based alternatives to common petrol‐based stabilisers. For this purpose, in this study, plant extracts were incorporated into poly‐lactic acid films (PLA) at different concentrations. The films’ UV absorbance and migration into packed food was analysed via photometric assays (ABTS radical cation scavenging capacity assay, β‐carotene assay) and GC–MS analysis. Furthermore, the synergistic antioxidant effects of various combinations of extracts and isolated active compounds were determined. This way, antioxidant effects can be increased, allowing for a highly effective use of resources. All extracts were successfully incorporated into PLA films and showed notable photoabsorbing effects, while no migration risk was observed. Depending on extract combinations, high synergistic effects of up to 726% can be utilised to improve the effectiveness of bio‐based extracts. This applies particularly to tomato paste and Aesculus hippocastanum extracts, which overall show high synergistic and antioxidant effects in combination with each other and with isolated active compounds. The study shows that it is possible to create safe bio‐based antioxidant films which show even improved properties when using highlighted target combinations.
Polymer fibers with liquid crystals (LCs) in the core have potential as autonomous sensors of airborne volatile organic compounds (VOCs), with a high surface-to-volume ratio enabling fast and sensitive response and an attractive non-woven textile form factor. We demonstrate their ability to continuously and quantitatively measure the concentration of toluene, cyclohexane, and isopropanol as representative VOCs, via the impact of each VOC on the LC birefringence. The response is fully reversible and repeatable over several cycles, the response time can be as low as seconds, and high sensitivity is achieved when the operating temperature is near the LC-isotropic transition temperature. We propose that a broad operating temperature range can be realized by combining fibers with different LC mixtures, yielding autonomous VOC sensors suitable for integration in apparel or in furniture that can compete with existing consumer-grade electronic VOC sensors in terms of sensitivity and response speed.
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation.
Die Analytik ist zwar ein grundlegendes Thema innerhalb der Chemie, hat es aber ganz schön in sich. Aber keine Sorge, Ulf Ritgen erklärt Ihnen in diesem Buch was Sie zur Analytischen Chemie Wissen sollten. Wie erhält man eigentlich analytische Infos? Welche Standards gibt es? Und wie sollte man überhaupt mit den Stoffgemischen umgehen? All diese Grundlagen werden ausführlich erläutert. Aber auch die Anwendungsgebiete und Methoden kommen keinesfalls zu kurz. Egal ob Gravimetrie, Titration, Fällung oder Konduktometrie, endlich wird alles verständlich erklärt. Jetzt können Prüfung und Praktikum kommen! (Verlagsangaben)
This volume of the series Springer Briefs in Space Life Sciences explains the physics and biology of radiation in space, defines various forms of cosmic radiation and their dosimetry, and presents a range of exposure scenarios. It also discusses the effects of radiation on human health and describes the molecular mechanisms of heavy charged particles’ deleterious effects in the body. Lastly, it discusses countermeasures and addresses the vital question: Are we ready for launch?
Written for researchers in the space life sciences and space biomedicine, and for master’s students in biology, physics, and medicine, the book will also benefit all non-experts endeavoring to understand and enter space.
The present thesis elucidates the development of (i) a series of small molecule inhibitors reacting in a covalent-irreversible manner with the targeted proteases and (ii) a fluorescently labeled activity-based probe as a pharmacological tool compound for investigation of specific functions of the mentioned enzymes in vitro. Herein, the rational design, organic synthesis and quantitative structure-activity-relationships are described extensively.
Multiwalled carbon nanotubes (MWCNTs) were easily and efficiently functionalised with highly cross-linked polyamines. The radical polymerisation of two bis-vinylimidazolium salts in the presence of pristine MWCNTs and azobisisobutyronitrile (AIBN) as a radical initiator led to the formation of materials with a high functionalisation degree. The subsequent treatment with sodium borohydride gave rise to the reduction of imidazolium moieties with the concomitant formation of secondary and tertiary amino groups. The obtained materials were characterised by thermogravimetric analysis (TGA), elemental analysis, solid state 13C-NMR, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), potentiometric titration, and temperature programmed desorption of carbon dioxide (CO2-TPD). One of the prepared materials was tested as a heterogeneous base catalyst in C–C bond forming reactions such as the Knoevenagel condensation and Henry reaction. Furthermore, two examples concerning a sequential one-pot approach involving two consecutive reactions, namely Knoevenagel and Michael reactions, were reported.
The development of metals tailored to the metallurgical conditions of laser-based additive manufacturing is crucial to advance the maturity of these materials for their use in structural applications. While efforts in this regard are being carried out around the globe, the use of high strength eutectic alloys have, so far, received minor attention, although previous works showed that rapid solidification techniques can result in ultrafine microstructures with excellent mechanical performance, albeit for small sample sizes. In the present work, a eutectic Ti-32.5Fe alloy has been produced by laser powder bed fusion aiming at exploiting rapid solidification and the capability to produce bulk ultrafine microstructures provided by this processing technique.
Process energy densities between 160 J/mm³ and 180 J/mm³ resulted in a dense and crack-free material with an oxygen content of ~ 0.45 wt.% in which a hierarchical microstructure is formed by µm-sized η-Ti4Fe2Ox dendrites embedded in an ultrafine eutectic β-Ti/TiFe matrix. The microstructure was studied three-dimensionally using near-field synchrotron ptychographic X-ray computed tomography with an actual spatial resolution down to 39 nm to analyse the morphology of the eutectic and dendritic structures as well as to quantify their mass density, size and distribution. Inter-lamellar spacings down to ~ 30–50 nm were achieved, revealing the potential of laser-based additive manufacturing to generate microstructures smaller than those obtained by classical rapid solidification techniques for bulk materials. The alloy was deformed at 600 °C under compressive loading up to a strain of ~ 30% without damage formation, resulting in a compressive yield stress of ~ 800 MPa.
This study provides a first demonstration of the feasibility to produce eutectic Ti-Fe alloys with ultrafine microstructures by laser powder bed fusion that are suitable for structural applications at elevated temperature.
This work presents the development of a measuring system for the quality control of ultrapure water. The new systems combines ozonation and UV radiation for the oxidation of organic substances. The change in conductivity caused by the oxidation is furthermore correlated with the TOC of the solution.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.
Toshiyuki Fukao
(2020)
Coumarin as a structural component of substrates and probes for serine and cysteine proteases
(2020)
Surface-enhanced Raman spectroscopy (SERS) with subsequent chemometric evaluation was performed for the rapid and non-destructive differentiation of seven important meat-associated microorganisms, namely Brochothrix thermosphacta DSM 20171, Pseudomonas fluorescens DSM 4358, Salmonella enterica subsp. enterica sv. Enteritidis DSM 14221, Listeria monocytogenes DSM 19094, Micrococcus luteus DSM 20030, Escherichia coli HB101 and Bacillus thuringiensis sv. israelensis DSM 5724. A simple method for collecting spectra from commercial paper-based SERS substrates without any laborious pre-treatments was used. In order to prepare the spectroscopic data for classification at genera level with a subsequent chemometric evaluation consisting of principal component analysis and discriminant analysis, a pre-processing method with spike correction and sum normalisation was performed. Because of the spike correction rather than exclusion, and therefore the use of a balanced data set, the multivariate analysis of the data is significantly resilient and meaningful. The analysis showed that the differentiation of meat-associated microorganisms and thereby the detection of important meat-related pathogenic bacteria was successful on genera level and a cross-validation as well as a classification of ungrouped data showed promising results, with 99.5 % and 97.5 %, respectively.