Blood-derived products (BP) like citrate-platelet-rich plasma (CPRP) or hyperacute serum (HAS) are known to contain many growth factors. Combined mitogenic and DNA damaging stimuli might lead to increased senescent cell burden and altered senescence-associated secretory pheno-type (SASP). Therefore, the senescent state was extensively tested by γH2AX staining, p21 Q-PCR and western blot, growth curves and senescence associated ß-galactosidase staining. Two main treatments with BP were performed early (immediately after etoposide) and late (after addition-al 11days). Effects of the BP treatment was evaluated by IL-6 and IL-8 measurement as well as collagen (COL1) and p21 mRNA expression. Additionally, XTT assays, cell size measurements, viability assays, and cell number calculations were performed. HAS treated cells in early treat-ment had the lowest observed IL-6 and IL-8. In contrast, there was a clear inflammatory response for IL-8 on HAS and CPRP treated cells in late treatment. For COL1 expression an upregulation in early treatment could be shown, meanwhile cells in the late treatment group remained unaf-fected. In CPRP treated cells, the COL1 expression decreased. All in all, BP treatment seems to have slightly positive effects regarding skin rejuvenation.

Relativistic shocks are one of the most plausible sites of the emission of strongly variable, polarized multi-wavelength emission from relativistic jet sources such as blazars, via diffusive shock acceleration (DSA) of relativistic particles. This paper summarizes recent results on a self-consistent coupling of diffusive shock acceleration and radiation transfer in blazar jets. We demonstrate that the observed spectral energy distributions (SEDs) of blazars strongly constrain the nature of hydromagnetic turbulence responsible for pitch-angle scattering by requiring a strongly energy-dependent pitch-angle mean free path. The prominent soft X-ray excess (``Big Blue Bump'') in the SED of the BL Lac object AO 0235+164 can be modelled as the signature of bulk Compton scattering of external radiation fields by the thermal electron population, which places additional constraints on the level of hydromagnetic turbulence. It has further been demonstrated that internal shocks propagating in a jet pervaded by a helical magnetic field naturally produce polarization-angle swings by 180$^o$, in tandem with multi-wavelength flaring activity, without requiring any helical motion paths or other asymmetric jet structures. The specific application of this model to 3C279 presents the first consistent, simultaneous modeling of snap-shot SEDs, multi-wavelength light curves and time-dependent polarization signatures of a blazar during a polarization-angle (PA) rotation. This model has recently been generalized to a lepto-hadronic model, in which the high-energy emission is dominated by proton synchrotron radiation. It is shown that in this case, the high-energy (X-ray and $\gamma$-ray) polarization signatures are expected to be significantly more stable (not showing PA rotations) than the low-energy (electron-synchrotron) signatures.

Expanding previous efforts to survey the visual opsin repertoires of the Hemiptera, this study confirms that homologs of the UV- and LW-opsin subfamilies are conserved in all Hemiptera, while the B-opsin subfamily is missing from the Heteroptera and subgroups of the Sternorrhyncha and Auchenorrhyncha, i.e. aphids (Aphidoidea) and planthoppers (Fulgoroidea), respectively. Unlike in the Heteroptera, which are characterized by multiple expansions of the LW-opsin subfamily, the lack of B-opsin correlates with the presence of tandem-duplicated UV-opsins in aphids and planthoppers. Available data on organismal wavelength sensitivities and retinal gene expression patterns lead to the conclusion that, in both groups, one UV-opsin paralog shifted from ancestral UV peak sensitivity to derived blue sensitivity, thereby compensating for the lost B-opsin. Two parallel bona fide tuning site substitutions compare to 18 non-corresponding amino acid replacements in the blue-shifted UV-opsin paralogs of aphids and planthoppers. Most notably, while the aphid blue-shifted UV-opsin clade is characterized by a replacement substitution at one of the best-documented UV/blue tuning sites (Rhodopsin site 90), the planthopper blue-shifted UV-opsin paralogs retained the ancestral lysine at this position. The combined findings identify aphid and planthopper UV-opsins as a new valuable data sample for studying adaptive opsin evolution.

Electrochemical-mechanical interactions, in particular pressure-induced ones, have been identified to be a cause for lithium-plating in lithium-ion cells. Mechanically-induced porosity inhomogeneities in the separator layers due to electrode expansion during charging especially lead to cell internal balancing currents and can cause localized plating. To identify cell-format and cell-material dependent mechanical weak spots, a layer-resolved mechanical simulation of different cell types and cell-material combinations is presented in this work. The simulation results show distinctive layer strain patterns for different cell-types that coincide with localized lithium-plating found in post-mortem cells. Additionally, the effects of cell bracing in battery modules is investigated and a method to mitigate the increased layer strain due to bracing counterforces is proposed that also increases cell energy density for hardcase-type automotive cells.

In this paper, the columnar supramolecular aggregates of photosensitive star-shaped azobenzenes with benzene-1,3,5-tricarboxamide core and azobenzene arms are analysed theoretically applying a combination of computer simulation techniques. Without a light stimulus, the trans-stars build one-dimensional columns of stacked molecules during the first stage of the noncovalent association. These columnar aggregates represent the structural elements of more complex experimentally observed morphologies -- fibers, spheres, gels and others. Upon UV light exposure, the azobenzene arms isomerise from thermodynamically stable planar trans- to a metastable kinked cis-state influencing the aggregate morphology. Here, we determine the most favourable mutual orientations of the \textit{trans}-stars in the stack in terms of (i) the pi-pi distance between the cores lengthwise the aggregate, (ii) the star slipped displacements and (iii) the rotation promoting the helical twist and chirality of the aggregate by calculating the binding energy diagrams using density functional theory. The model predictions are further compared with available experimental data. The intermolecular forces responsible for the stability of the stacks made of trans-azobenzene stars in crystals are quantified using Hirshfeld surface analysis. Finally, to characterize the self-assembly mechanism of such stars in solution, we calculate the hydrogen bond lengths, the normalized dipole moment and the binding energies as the functions of the columnar length using molecular dynamics trajectories, and conclude about the cooperative nature of this process.

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTC), or extracellular vesicles (EV) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

The WORLD3 world model, which served as the basis for The Club of Rome report The Limits to Growth (1972), was criticized, among other things, for not being able to simulate social interactions. In order to remedy this shortcoming, a research group led by Karl Deutsch at the Berlin Science Center developed a far more comprehensive model between 1979 and 1988 entitled GLOBUS, which was supposed to be able to include political developments in the calculation. This article aims to explain the hopes that were attached to the creation of a further world model and the means by which attempts were made to assert its results. To this end, three genealogical lines of the model -I. as part of the world modeling community, II. as part of quantitative international relations research, III. as part of Karl Deutsch's cybernetic-political science research- will be presented. The data basis and the functioning of GLOBUS are then described. Finally, section VI is devoted to the research group's efforts to make the model "effective".

The proposed method deals with the problem of data privacy and sharing when processing personal mobility tracking data. Previous methods concentrate on producing highly detailed data on short-term and restricted areas, e.g. for autonomous driving scenarios. Another possibility consists of city-wide scales and beyond, that are used to predict general traffic flows. The presented approach takes the tracked mobility behavior of individuals to create coherent new mobility data that reflects the long-term mobility behavior of the person, guaranteeing location persistency and sound embedding within the point-of-interest structure of the observed area. After an analysis and clustering step with the original data, the area is distributed into a geospatial grid structure (H3 is used here), and the neighborhood relationships between the grids are interpreted as a graph. A feed-forward-autoencoder and a graph encoding-decoding network generate a latent space representation of the area. The original clustered data is associated with their respective H3 grids. With a greedy algorithm approach and concerning privacy strategies, new combinations of grids are top-level patterns for individual mobility behavior. Concrete locations are found and connected within the grids based on the original data. The described method is then applied to a study with 1000 participants from the city of Munich in Germany, and the results are described, showing the application of the approach in generating synthetic data, enabling further research on individual mobility behavior and patterns. The result is a sharable dataset on the same abstraction level as the input data, which makes it interesting, particularly for machine learning applications.

Intermetallic alloys like e.g. Iron-Aluminides, Titanium-Aluminides or Molybdenum- Silizides are prospective materials for high-temperature applications. For additive manufacturing (AM) intermetallic structural materials are particularly challenging due to their high melting points, oxygen susceptibility and low temperature brittleness. The feasibility of manufacturing intermetallic Mo-Si-B alloys with the laser additive manufacturing process of direct energy deposition (DED) is demonstrated and recent results in characterizing rapidly solidified material with respect to correlations between process, composition and microstructures are presented. The possibility to dope the material with Yttrium oxide (Y2O3) for dispersion is successfully demonstrated. Current challenges, e.g. homogenous distribution of alloying elements and applicability are addressed.

A recent paradigm shift in diagnostics of medulloblastoma allows the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow better clinical management for therapies targeting druggable mutations, but also offers a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery, radio- and chemotherapy, but also controversial theories on the cell of origin, animal models and the use of liquid biopsy.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Granular superconductivity at high temperatures in graphite can emerge at certain two-dimensional (2D) stacking faults (SFs) between regions with twisted (around the c-axis) or untwisted crystalline regions with Bernal (ABA...) and/or rhombohedral (ABCABCA...) stacking order. One way to observe experimentally such 2D superconductivity is to measure the frozen magnetic flux produced by a permanent current loop that remains after removing an external magnetic field applied normal to the SFs. Magnetic force microscopy was used to localize and characterize such a permanent current path found in one natural graphite sample out of ∼50 measured graphite samples of different origins. The position of the current path drifts with time and roughly follows a logarithmic time dependence similar to the one for flux creep in type II superconductors. We demonstrate that a ≃10nm deep scratch on the sample surface at the position of the current path causes a change in its location. A further scratch was enough to irreversibly destroy the remanent state of the sample at room temperature. Our studies clarify some of the reasons for the difficulties of finding a trapped flux in remanent state at room temperature in graphite samples with SFs.

A probe of a patient, seeking help in an emergency ward of a French hospital in late December 2019 because of Influenza like symptoms, was retrospectively tested positive to COVID-19. Despite the early appearance of the virus in Europe, the prevalence and virulence appeared to be low for several weeks, before the spread and severity of symptoms increased exponentially, yet with marked spatial and temporal differences. Here, we compare the possible linkages between peaks of fine particulate matter (PM2.5) and the sudden, explosive increase of hospitalizations and mortality rates in the Swiss Canton of Ticino, and the Greater Paris and London regions. We also discuss the influence of Saharan dust intrusions on the COVID-19 outbreak observed in early 2020 on the Canary Islands. We find that high PM2.5 concentrations – possibly favored by air temperature inversions or Saharan dust intrusions – are not only modulating but even more so boosting severe outbreaks of COVID-19. We conclude that the overburdening of the health services and hospitals as well as the high over-mortality observed in various regions of Europe in spring 2020 can be linked to peaks of PM2.5 and likely particular weather situations that have favored the spread and enhanced the virulence of the virus. In the future, we recommend to monitor not only the prevalence of the virus, but also to consider the occurrence of weather situations that can lead to sudden, very explosive COVID-19 outbreaks.

Horseshoe crabs represent the most ancestral chelicerate lineage characterized by marine ecology and the possession of lateral compound eyes. While considered living fossils, recent studies reported an unusual number of Pax6 transcription factor genes in the Atlantic horseshoe crab Limulus polyphemus. Pax genes encode a family of ancient metazoan transcription factors, which comprise seven subfamilies. Among these, the members of the Pax6 subfamily confer critical functions in the development of the head, the visual system, and further body plan components. Arthropods are characterized by two Pax6 subfamily homologs that were discovered in Drosophila and named eyeless (ey) and twin of eyeless (toy). However, whole genome sequence searches uncovered three homologs of ey and two homologs of toy in L. polyphemus. These numbers are explained by the occurrence of three whole genome duplications (WGD) in the lineage to the last common ancestor of L. polyphemus and its closely related three additional members of the extant horseshoe crab species cluster. Here we report comparative sequence evidence for the functional conservation of the five L. polyphemus Pax6 transcription factor homologs. Our analyses reveal that all paralogs are conserved in the approximately 135 million-year-old horseshoe crab species cluster and that they evolve under strong purifying selection. These findings identify subfunctionalization as the likeliest post-WGD outcome for the five Pax6 homologs. While awaiting confirmation by gene expression studies, this scenario would reconcile the discrepancy between the WGD-expanded gene repertoires and phenotypic stasis in the horseshoe crabs.

Cold-water coral reefs are rich, yet fragile ecosystems found in colder oceanic waters. Knowledge of their spatial distribution on continental shelves, slopes, seamounts and ridge systems is vital for marine spatial planning and conservation. Cold-water corals frequently form conspicuous carbonate mounds of varying sizes, which are identifiable from multibeam echosounder bathymetry and derived geomorphometric attributes. However, the often large number of mounds makes manual interpretation and mapping a tedious process. We present a methodology that combines image segmentation and random forest spatial prediction with the aim to derive maps of carbonate mounds and an associated measure of confidence. We demonstrate our method based on multibeam echosounder data from Iverryggen on the mid-Norwegian shelf. We identified the image-object mean planar curvature as the most important predictor. The presence and absence of carbonate mounds is mapped with high accuracy (overall accuracy = 84.4%, sensitivity = 0.827 and specificity = 0.866). Spatially-explicit confidence in the predictions is derived from the predicted probability and whether the predictions are within or outside the modelled range of values and is generally high. We plan to apply the showcased method to other areas of the Norwegian continental shelf and slope where MBES data have been collected with the aim to provide crucial information for marine spatial planning.

The potential of the Additive Manufacturing technologies is impeded by the surface finish obtained on the as-manufactured material. Therefore, the influence of various surface treatments, commonly applied to space hardware, on the mechanical properties of three selected metallic alloys (SS316L, AlSi10Mg, Ti6Al4V) prepared by using Selective Laser Melting (SLM) and Electron Beam Melting (EBM) additive manufacturing processes have been investigated. Within this study, SLM using EOS M400 and EOS M280 equipment and in addition EBM using an ARCAM Q20 machine have been applied for sample manufacturing. A half-automated shot-peening process followed by a chemical and/or electrochemical polishing or Hirtisation® process has been applied in order to obtain lower surface roughness compared to their as-received states. Special emphasize has been taken on their tensile, fatigue, and fracture toughness properties. In addition, their stress corrosion cracking (SCC) behaviour including microstructural analysis using HR-SEM have been investigated.

High-content fluorescence microscopy combines the efficiency of high-throughput techniques with the ability to extract quantitative information from biological systems. The planarian community has developed sensitive and robust assays for whole animals, yet cell based assays, despite their practical aspects, have not been explored to the same extent. Here we describe a modular collection of detailed protocols adapted for fixed planarian cells that enable multiplexed measurements of biomarkers in microwell plates. Methods include the detection of RNA transcripts by RNA fluorescent in situ hybridization combined with tyramide signal amplification using hapten-labeled riboprobes. In addition, immunocytochemical protocols for quantifying proliferating cells by the detection of phosphorylated histone H3 as well as 5-bromo-2'-deoxyuridine incorporation into the nuclear genome are described. The assays are compatible with planarians of virtually any size, as the tissue is disaggregated into a single cell suspension before fixation and staining. By sharing many reagents with established planarian whole mount staining protocols, preparation of samples for high-content microscopy adoption requires little additional investment. Recommendations for successful experimental workflows and common sources of errors are discussed.

While current video quality assessment research predominantly revolves around resolutions of 4K and beyond, targeted at Ultra High-Definition (UHD) displays, effective video quality for mobile video streaming remains primarily within the range of 480p to 1080p. In this study, we conducted a comparative analysis of the Quality of Experience (QoE) for widely implemented video codecs on mobile devices, specifically Advanced Video Coding (AVC), its successor High-Efficiency Video Coding (HEVC), and Google's VP9. Our choice of 720p video sequences from a newly developed database, all with identical bitrates, aimed to maintain a manageable subjective assessment duration, capped at 35-40 minutes. To mimic real-time network conditions, we generated stimuli by streaming original video clips over a controlled emulated setup, subjecting them to eight different packet loss scenarios. We evaluated the quality and structural similarity of the distorted video clips using objective metrics, including Video Quality Metric (VQM), Peak Signal-to-Noise Ratio (PSNR), Video Multi-Method Assessment Fusion (VMAF), and Multi-Scale Structural Similarity Index (MS-SSIM). Subsequently, we collected subjective ratings through a custom mobile application developed for Android devices. Our findings revealed that VMAF accurately represents the degradation in video quality compared to other metrics. Moreover, in most cases, HEVC exhibits an advantage over both AVC and VP9 under low packet loss scenarios. However, it is noteworthy that in our test cases, AVC outperformed HEVC and VP9 in scenarios with high packet loss, based on both subjective and objective assessments. Our observations further indicate that user preferences for the presented content contribute to video quality ratings, emphasizing the importance of additional factors that influence the perceived video quality of end-users.

Thermal analysis is widely employed for the characterization of nanomaterials. It encompasses a variety of techniques that allow the evaluation of the physicochemical properties of a material by monitoring its response under controlled temperature. In the case of carbon nanomaterials, such as carbon nanotubes and graphene derivatives, thermogravimetric analysis (TGA) is particularly useful to determine the quality and stability of the sample, presence of impurities and the degree of functionalization or doping after post-synthesis treatments. Furthermore, TGA is widely used to evaluate the thermal stability against oxidation by air, which can be for instance enhanced by the purification of the material and by nitrogen doping, finding application in areas where a retarded combustion of the material is required. Herein, we have evaluated key parameters that play a role in the data obtained from TGA. Within this study we show that the thermogravimetric curve of carbon nanomaterials is greatly influenced by these parameters. This is important in terms of data recording and their analysis, since a poor control of the conditions of measurement might lead to false conclusions. We highlight this by analyzing different samples of graphene and carbon nanotubes where both thermal stability and sample purity assessment are found to be dependent on the employed TGA parameters. Finally, a set of TGA parameters are recommended for the analysis of carbon nanomaterials to obtain reliable data.¡

Chironomus riparius is a well-established model organism in various fields such as ecotoxicology and ecology, and therefore environmental preferences, ecological interactions and metabolic traits are well-studied. With the recent publication of a high-quality draft genome, as well as different population genetic parameters such as mutation and recombination rate, the species can be used as an alternative to the Drosophila models in experimental population genomics or molecular ecology. To facilitate access to this promising experimental model species for a wider range of researchers, we describe experimental methods to first create and sustain long term cultures of C. riparius and then use them to perform repeatable and comparable experiments for various research questions.

Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in non-diabetics or individuals with diabetes and when combined is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases and dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the anti-diabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilising a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms such as sympathoinhibition which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in diabetic and non-diabetic subjects in both pre-clinical and clinical settings by improving hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy. (188 Words)

Despite the implementation of control strategies, the invasive parasitic mite Varroa destructor remains one of the principal causes of honey bee (Apis mellifera) colony losses in numerous countries. For this reason, the parasite represents a serious threat to beekeeping and to agro-ecosystems that benefit from the pollination services provided by honey bees. Numerous selection programmes have been initiated over the last three decades with the aim of promoting the establishment of balance in the host–parasite relationship and, thus, helping European honey bees to survive in the presence of the parasite without the need for acaricide treatments. Such programmes have focused on either selective breeding for putative resistance traits or natural selection. To date, no clear overview of these attempts has been available, which has prevented building on past successes or failures and, therefore, hindered the development of a sustainable strategy for solving the V. destructor problem. In the present study, we review past and current selection strategies, report on their outcomes and discuss their limitations. Based on this state-of-the-art knowledge, we propose a strategy for increasing response to selection and colony survival against V. destructor infestations. Developing in-depth knowledge regarding the selected traits, optimising selection programmes and communicating their outcomes are all crucial to our efforts to establish a balanced relationship between the invasive parasite and its new host.

Laser powder bed fusion (LPBF) is an additive manufacturing process employed in many industries, for example for aerospace, automotive and medical applications. In these sectors, mainly nickel-, aluminum- and titanium-based alloys are used. In contrast, the mechanical engineering industry is interested in more wear-resistant steel alloys with higher hardness, both of which can be achieved with a higher carbon content, like in high-speed steels. Since these steels are susceptible to cracking, preheating needs to be applied during processing by LPBF. In a previous study, we applied a base plate preheating temperature of 500 °C for HS6-5-3-8 with 1.3 % carbon content. We were able to manufacture dense (p > 99.9 %) and crack-free parts from HS6-5-3-8 with a hardness > 62 HRC (as built) by LPBF. In this study, we investigate the influence of preheating temperatures up to 600 °C on hardness and microstructure dependent on part height for HS6-5-3-8. The microstructure was studied by light optical microscopy (LOM), scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The analysis of hardness and microstructure at different part heights is necessary because state-of-the-art preheating systems induce heat only into the base plate. Consequently, parts are subjected to temperature gradients and different heat treatment effects depending on part height during the LPBF process.

Studying various marine biomineralized ultrastructures reveals the appearance of common architectural designs and building blocks in materials with fascinating mechanical properties that match perfectly to their biological tasks. Advanced mechanical properties of biological materials are attributed to evolutionary optimized molecular architectures and structural hierarchy. One example which has not yet been structurally investigated in great detail is the shell of Mytilus edulis L. (Finnish blue mussel) found in the archipelago of SW-Finland. Through a combination of various state-of-the-art techniques such as high-resolution electron microscopy imaging, Fourier-transformed infrared spectroscopy, powder X-ray diffraction, synchrotron wide-angle X-ray diffraction, nanoindentation and protein analysis, both the inorganic mineralized components as well as the organic-rich matrix were extensively characterized. We found very similar ultra-architecture across the shell of M. edulis L. as compared to the widely studied and closely related M. edulis. However, we also found interesting differences, for instance in the thickness and degree of orientation of the mineralized layers indicating dissimilar properties and related alterations in the biomineralization processes. Our results show that the shell of M. edulis L. has a gradient of mechanical properties, with the increase in the stiffness and the hardness from anterior to the posterior region of the shell. The shell is made from distinct and recognizable mineralized layers each varying in thickness and microstructural features. At posterior regions of the shell, moving from dorsal to ventral side, these layers are an oblique prismatic layer, a prismatic layer and a nacreous layer, in which the oblique prismatic layer is found to be the main and thickest mineralized layer of the shell. Probing the calcified rods in the oblique prismatic layer using high resolution SEM imaging revealed opening of channels with a diameters of 40-50 nm and lengths up to a micrometer extending through the rods. The chitin and protein have been found to be the main component of the organic-rich interfacial matrix as expected. Protein analysis showed two abundant proteins with sizes around 100 kD and 45 kD which likely not only regulates biomineralization and adhesion of the crystals but also governing the intrinsic-extrinsic toughening in the shell. Overall, this detailed analysis provides new structural insights into biomineralization of marine shells in general.

In this paper, experiences of the last 20 years with the PERALS-technique are described. PERALS stands for Photo Electron Rejecting Alpha Liquid Scintillation. This LSC-technique was developed by Jack McDowell in the 70ies and is a powerful technique for the analyses of many natural alpha nuclides. The principle is based on a selective extraction of the radionuclide from the water phase by means of a complexing or ion pair reagent. The extractant contains also a suitable cocktail for the scintillation counting. Therefore, the extract can be analysed directly after the extraction step. After removing quenchers, such as oxygen, and the proper setting of a pulse shape discriminator, alpha pulses can be counted with a photomultiplier. The paper describes the development of robust analysis schemes for the determination of traces of polonium, radon, radium, strontium, thorium, uranium and other actinides in water samples (groundwater, rain water, river water, drinking water, mineral water, sea water).

Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.

Advanced methods of treatment are needed to fight the threats of virus-transmitted deseases and pandemics. Often they are based on an improved biophysical understanding of virus replication strategies and processes in their host cells. For instance, an essential component of the replication of the Hepatitis C virus (HCV) proceeds under the influence of non-structural HCV proteins (NSPs) that are anchored to the endoplasmatic reticulum (ER), such as the NS5a protein. The diffusion of NSPs has been studied by in-vitro fluorescence recovery after photobleaching (FRAP) experiments. The diffusive evolution of the concentration field of NSPs on the ER can be described by means of surface partial differential equations (sufPDE). Knodel et al, Viruses 2018, 10, 28 estimated the diffusion coefficient of the NS5a protein by minimizing the discrepancy of an extended set of sufPDE simulations and experimental FRAP time series data. Here, we provide a scaling analysis of the sufPDEs that describe the diffusive evolution of the concentration field of NSPs on the ER. This analysis provides an estimate of the diffusion coefficient that is based only on the ratio of the membrane surface area in the FRAP region and its contour length. The quality of this estimate is explored by comparison to numerical solutions of the sufPDE for a flat geometry and for ten different 3D embedded 2D ER grids that are derived from fluorescence z-stack data of the ER. Finally, we apply the new data analysis to the experimental FRAP time-series data analyzed in our previous paper, and we discuss the opportunities of the new approach.

The manual muscle test (MMT) is a flexible diagnostic tool, which is used in many disciplines, applied in several ways. The main problem is the subjectivity of the test. The MMT in the version of a “break test” depends on the tester’s force rise and the patient’s ability to resist the applied force. As a first step, the investigation of the reproducibility of the testers’ force profiles is required for valid application. The study examined the force profiles of n=29 testers (n=9 experiences (Exp), n=8 little experienced (LitExp), n =12 beginners (Beg)). The testers performed 10 MMTs according to the test of hip flexors, but against a fixed leg to exclude the patient’s reaction. A handheld device recorded the temporal course of the applied force. The results show significant differences between Exp and Beg concerning the starting force (padj=0.029), the ratio of starting to maximum force (padj=0.005) and the normalized mean Euclidean distances between the 10 trials (padj=0.015). The slope is significantly higher in Exp vs. LitExp (p=0.006) and Beg (p=0.005). The results also indicate that experienced testers show inter-tester differences and partly even a low intra-tester reproducibility. That highlights the necessity of an objective MMT-assessment. Furthermore, an agreement on a standardized force profile is required – a suggestion is given.

Cesiumtrifluoroacetate (CsTFA) is a key chemical for RNA-based stable isotope analyses to link the structure and function of microbial communities. We report a protocol to easily synthesize CsTFA from Cesiumcarbonate (Cs₂CO₃₎ and Trifluoroacetate (TFA) and show that self-synthesized CsTFA behaves similar to commercial CsTFA in the separation of isotopically labelled and unlabelled E. coli RNA.

Facing unprecedented global declines in the extent and integrity of ecosystems, the 15^th UN Biodiversity Conference (COP-15) in Kunming, China, presents an opportunity for transformative change. However, a lack of consensus on two key issues – resource mobilization and Access and Benefit Sharing (ABS) associated with Digital Sequence Information (DSI) – risks stalling negotiations for an ambitious ‘Post-2020 Global Biodiversity Framework’ as the next 10-year strategic plan under the Convention on Biological Diversity. We highlight systemic misconceptions concerning the financing of biodiversity and the burden this places on the ABS system. In the context of DSI, we caution that conflating ABS with resource mobilization risks disrupting modern science policy built on open access, with potentially severe ramifications for scientific research and innovation. To resolve these tensions, we call for a recalibration of discussions on ABS in order to maximize the value delivered by biodiversity for all of society, including indigenous peoples and local communities.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.

There is a growing need for an area-wide knowledge of SOC contents in agricultural soils at field scale for food security, monitoring long-term changes related to soil health and climate change. In Germany, large-scale SOC maps are mostly available with a spatial resolution of 250 m to 1 km2. The nationwide availability of both digital elevation models at various spatial resolutions and multi-temporal satellite imagery enables the derivation of multi-scale terrain attributes and Landsat-based multi-temporal soil reflectance composites (SRC) as explanatory variables. On the example of an Bavarian test of about 8000 km2, the scale-specific dependencies between the representativeness of 220 soil samples and different aggregation levels of the explanatory variables were analyzed for their scale-specific predictive power. The aggregation levels were generated by applying a region-growing segmentation procedure, the SOC content prediction was realized by the Random Forest algorithm. In doing so, established approaches of (geographic) object-based image analysis (GEOBIA) and machine learning were combined. The modeling results revealed scale-specific differences. Compared to terrain attributes, the use of SRC parameters lead to a significant model improvement at large field-related scale levels. The joint use of both terrain attributes and SRC parameters resulted in further model improvements. The best modeling variant is characterized by an accuracy of R2=0.84 and RMSE=1.99.

Due to resource constraints, most Diamond Open Access journals publish less than 25 articles per year, and 75% of journals are not able to provide their content in XML and HTML, primarily providing only PDFs (Bosman et al., 2021, p. 7-8). In order to keep up with larger commercial publishers, a high degree of automation and streamlining of processes is necessary. The Open Source Academic Publishing Suite (OS-APS) project funded by the German Federal Ministry of Education and Research aims to achieve this. OS-APS automatically extracts the underlying XML from Word manuscripts and offers optimization and export options in various formats (PDF, HTML, EPUB). The professional corporate design, e.g., of the PDFs, is managed automatically by using templates or creating one's own using a Template Development Kit. OS-APS will also connect to scholarly-led and community-driven publishing platforms such as Open Journal Systems (OJS), Open Monograph Press (OMP), and DSpace: the software will be able to be integrated into a wide range of publication processes, whether at small, low-resource commercial Open Access Publishers, or institutional and Diamond Open Access Publishers. References: Bosman, J., Frantsvåg, J. E., Kramer, B., Langlais, P.‑C., & Proudman, V. (2021). Oa Diamond Journals Study. Part 1: Findings. https://doi.org/10.5281/zenodo.4558703

Prediction markets are heralded as powerful forecasting tools, but models to describe them often fail to capture the full complexity of the underlying mechanisms that drive price dynamics. To address this issue, we propose a model in which agents belong in a social network, have an opinion about the probability of a particular event to occur, and bet on the prediction market accordingly. Agents update their opinions about the event by interacting with their neighbours in the network, following the Deffuant model of opinion dynamics. Our results suggest that a simple market model that takes into account opinion formation dynamics is capable to replicate the empirical properties of historical prediction market time series, including volatility clustering and fat-tailed distribution of returns. Interestingly, the best results are obtained when there is the right level of variance in the opinions of the agents. Moreover, this paper provides a new way to indirectly validate opinion dynamics models against real data by using historical data obtained from PredictIt, an exchange platform whose data has never been used before to validate models of opinion diffusion.

Recent developments in mid-infrared (MIR) spectroscopic ellipsometry enabled by quantum cascade lasers (QCLs) resulted in a drastic improvement in signal-to-noise ratio compared to conventional thermal emitter based instrumentation. Thus, it was possible to reduce the acquisition time for high-resolution broadband ellipsometric spectra from multiple hours to less than 1 second. This opens up new possibilities for real-time in-situ ellipsometry in polymer processing. To highlight these evolving capabilities we demonstrate the benefits of a QCL based MIR ellipsometer by investigating single and multilayered polymer films. The molecular structure and reorientation of a 2.5m thin biaxially oriented polyethylene terephtalate film is monitored during a stretching process lasting 24.5 s to illustrate the perspective of ellipsometric measurements in dynamic processes. In addition, a polyethylene/ethylene vinyl alcohol/polyethylene multilayer film is investigated at continuously varying angle of incidence ( 0∘ – 50∘) in 17.2 s, highlighting an unprecedented sample throughput for the technique of varying angle spectroscopic ellipsometry in the MIR spectral range. The obtained results underline the superior spectral and temporal resolution of QCL ellipsometry and qualify this technique as suitable method for advanced in-situ monitoring in polymer processing.

In this contribution, we present a high-speed multiplex grating spectrometer based on a spectral coding approach that is founded on principles of compressive sensing. The spectrometer employs a single-pixel InGaAs detector to measure the signals encoded by an amplitude spatial light modulator (digital micromirror device, DMD). This approach leads to a speed advantage and multiplex sensitivity advantage atypical for standard dispersive systems. Exploiting the 18.2 kHz pattern rate of the DMD, we demonstrate 4.2 ms acquisition times for full spectra with a bandwidth of 450 nm (5250 cm-1 – 4300 cm-1; 1.9 µm – 2.33 µm). Due to the programmability of the DMD, spectral regions of interest can be chosen freely, thus reducing acquisition times further, down to the sub-millisecond regime. The adjustable resolving power of the system accessed by means of computer simulations is discussed, quantified for different measurement modes, and verified by comparison with a state-of-the-art Fourier-transform infrared spectrometer. We show measurements of characteristic polymer absorption bands in different operation regimes of the spectrometer. The theoretical multiplex advantage of 8 was experimentally verified by comparison of the noise behavior of the spectral coding approach and a standard line-scan approach.

Knowledge of the spatio-temporal occurrence of avalanche activity is critical for avalanche forecasting and hazard mapping. We present a near-real time automatic avalanche monitoring system that outputs detected avalanche polygons within roughly 10 min after Sentinel- 1 SAR data download. Our avalanche detection algorithm has an average probability of detection of 67.2 % with a false alarm rate averaging 45.9, with maximum POD's over 85 % and minimum FAR's of 24.9 % compared to manual detection of avalanches. The high variability in performance stems from the dynamic nature of snow in the Sentinel-1 data. After tuning parameters of the detection algorithm, we processed five years of Sentinel-1 images acquired over a 150 x 100 km large area in Northern Norway, with the best setup. Compared to a dataset of field-observed avalanches, 77.3 % were manually detectable. Using these manual detections as benchmark, the avalanche detection algorithm achieved an accuracy of 79 % with high POD's in cases of medium to large wet snow avalanches. For the first time, we can present a dataset of spatiotemporal avalanche activity over several winters from a large region. This unique dataset allows for research into the relationship between avalanche activity and triggering meteorological factors, mapping of avalanche prone areas and near-real time avalanche activity monitoring to assist public avalanche forecasting. Currently, the Norwegian Avalanche Warning Service is using our processing system for pre-operational use in three regions in Norway.

The authors introduce the GRASS GIS add-on module g.citation as an initial implementation of a fine-grained software citation concept. The module extends the existing citation capabilities of GRASS GIS, which until now only provide for automated citation of the software project as a whole, authored by the GRASS Development Team, without reference to individual persons. The functionalities of the new module enable individual code citation for each of the over 500 implemented functionalities, including add-on modules. Three different classes of citation output are provided in a variety human- and machine-readable formats. The implications of this reference implementation of scientific software citation for both for the GRASS GIS project and the OSGeo foundation are outlined.

Transport biofuels derived from biogenic material are used for substituting fossil fuels, thereby abating greenhouse gas (GHG) emissions. Numerous competing conversion options exist to produce biofuels, with differing GHG emissions and costs. In this paper analysis and modelling of the long-term development of GHG abatement and relative GHG abatement cost competitiveness between crop-based biofuels in Germany is carried out. Presently dominant conventional biofuels and advanced liquid biofuels were found not to be competitive compared to the substantially higher yielding options available: sugar beet based ethanol for the short to medium term least-cost option and Substitute Natural Gas (SNG) for the medium to long term. The competitiveness of SNG was found to depend highly on the emissions development of the power mix. Silage maize based biomethane was found competitive on a land area basis, but not on an energetic basis. Due to land limitations as well as cost and GHG uncertainty, a stronger focus on the land use of crop-based biofuels should be laid in policy.

Rikenella microfusus is an essential intestinal probiotic with great potential. The latest research shows that its imbalance in the intestinal flora is related to the occurrence of various diseases, such as intestinal diseases, immune diseases, and metabolic diseases. Rikenella may be a target or biomarker for some diseases, providing a new possibility for preventing and treating these diseas-es by monitoring and changing the abundance of Rikenella in the intestine. However, the current detection methods have disadvantages such as long detection time, complicated operation, and high cost, which seriously limit the possibility of clinical application of this new treatment method. Therefore, developing rapid and low-cost detection methods has become an urgent problem to be solved. In this study, we used Rikenella as the target bacterium, meanwhile including five other prominent gut bacteria Akkermansia muciniphila, Allobaculum stercoricanis, Blautia producta, Rose-buria intestinalis and Parabacteroides distasonis as control organisms. The aptamer library R.m-R13 was evolved with high specificity and strong affinity (Kd = 9.597 nM) in an iterative Cell-SELEX process after 13 rounds of selection. R. microfusus can efficiently be discriminated from other major gut bacteria in complex mixtures in different analysis techniques including fluorescence micros-copy or fluorometric suspension assays and even in human stool samples. These preliminary re-sults open new avenues towards the development of aptamer-based microbiome bio-sensing ap-plications for fast and reliable R. microfusus monitoring.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

The introduction of the Industrial Internet of Things (IIoT) has led to major changes in the industry. Thanks to machine data, business process management methods and techniques could also be applied to them. However, one data source has so far remained untouched: The network data of the machines. In the business environment, process mining, for example, has already been carried out based on network data, but the IIoT, with its particular protocols such as OPC UA, has yet to be investigated. With the help of design science research and on the shoulders of CRISP-DM, we first develop a framework for process mining in the IIoT in this paper. We then apply the framework to real-world IIoT network traffic data and evaluate the outcome and performance of our approach in detail. We find tremendous potential in network traffic data but also limitations. Among other things, due to the dependence on process experts and the existence of case IDs.

Analytical instruments used for scientific research and education are often expensive. This limitation poses a challenge for schools and educators in low-income countries to provide practical science training to students. To address this problem, the improvisation of analytical instruments and instructional materials has emerged as a viable solution. By incorporating practical experiments into science education, students have the opportunity to engage directly with scientific instruments, conduct investigations, and collect data. This hands-on approach fosters a deeper understanding of scientific principles, enhances critical thinking skills, and cultivates scientific mindsets among students. Herein, we review and discuss, step-by-step, the approach of using a smartphone for quantitative analysis, referred to as smartphone digital image colorimetry (SDIC). SDIC, with its practicality and accessibility, utilizes smartphone digital cameras for image acquisition and the freely available image processing programs, such as ImageJ and smartphone Apps, for image quantification. Using SDIC can enable students in low-income countries to develop essential scientific skills, including critical thinking, data interpretation, and an evidence-based approach to scientific research. By leveraging the ubiquity and affordability of smartphone technology, SDIC offers an accessible and cost-effective approach to practical science education, bridging the gap between theory and practice in resource-constrained settings.

Providing simultaneously autotrophic and heterotrophic carbon sources is a promising strategy to overcome the limits of autotrophic syngas fermentations. D-xylose and L-arabinose are particularly interesting as they can be obtained by the hydrolysis of lignocellulosic biomass. The individual conversion of varying initial concentrations of these pentoses and D-fructose as reference was studied with C. autoethanogenum in fully-controlled stirred-tank reactors with a continuous syngas supply. All mixotrophic batch processes showed increased biomass and product formation compared to an autotrophic reference process. Simultaneous CO and D-xylose or L-arabinose conversion was observed in contrast to D-fructose. In the mixotrophic batch processes with Larabinose or D-xylose, the simultaneous CO and sugar conversion resulted in high final alcohol to acid ratios of up to 58 g g-1. L-arabinose was superior as a mixotrophic carbon source because biomass and alcohol concentrations (ethanol and 2,3-butanediol) were highest, and significant amounts of meso-2,3-butanediol (>1 g L-1) in addition to D-2,3-butanediol (>2 g L-1) were solely produced with L-arabinose. Furthermore, C. autoethanogenum could not produce meso-2,3 butanediol under purely heterotrophic conditions. The mixotrophic production of meso-2,3-butanediol from Larabinose and syngas, both available from residual lignocellulosic biomass, is very promising for use as a monomer for bio-based polyurethanes or as an antiseptic agent.

For our research on droplet deformation and breakup in scaled high-pressure homogenizing units we developed a pressure stable inline droplet generator. It consists of an optically accessible flow channel with a combination of stainless steel and glass capillaries and a 3D printed orifice. The droplet size is determined online by live image analysis. The influence of the orifice diameter, the mass flow of the continuous phase and the mass flow of the disperse phase on the droplet diameter was investigated. Furthermore, the droplet detachment mechanisms were identified. Droplet diameters with small diameter fluctuation between 175 µm and 500 µm could be realized, which allows a precise adjustment of the Ca and We Number in the subsequent scaled high pressure homogenizer disruption unit. The determined influence of geometry and process parameters on the resulting droplet size and droplet detachment mechanism agreed well with literature on microfluidics. Furthermore, droplet trajectories in an exemplary scaled high-pressure homogenizer disruption unit are presented which show that the droplets can be reinjected on a trajectory close to the center axis or close to the wall, which should result in different stresses on the droplets.

Large volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics including immune responses follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to 3 years we have established a well characterized large segmental tibial bone defect ovine model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups in which all ovine segmental defects were treated with a bone grafting technique combined with a three-dimensionally printed medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold. The qualitative data set is based on osteoimmunological findings gained from IHC analyses of over >350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

Exoskeletons designed to assist patients with activities of daily living are becoming increasingly popular, but still are subject to research. In order to gather requirements for the design of such systems, long-term gait observation of the patients over the course of multiple days in an environment of daily living are required. In this paper a wearable all-in-one data acquisition system for collecting and storing biomechanical data in everyday life is proposed. The system is designed to be cost efficient and easy to use, using off-the-shelf components and a cloud server system for centralized data storage. The measurement accuracy of the system was verified, by measuring the angle of the human knee joint at walking speeds between 3 and 12 km/h in reference to an optical motion analysis system. The acquired data was uploaded to a cloud database via a smartphone application. Verification results showed that the proposed toolchain works as desired. The system reached an RMSE from 2.9° to 8°, which is below most of the comparable system. The system provides a powerful, scalable platform for collecting and processing biomechanical data, which can help to automize the generation of an extensive database for human kinematics.

Despite being small and simple structured in comparison to their victims, virus particles have the potential to harm severly and even kill highly developed species such as humans. To face upcoming virus pandemics, detailed quantitative biophysical understanding of intracellular virus replication mechanisms is inevitable. Unveiling the relationship of form and function might allow to determine putative attack points relevant for the systematic development of direct antiviral agents (DAA) and potent vaccines. Biophysical investigations of spatio-temporal dynamics of intracellular virus replication so far are rare. We are developing a framework to allow for fully spatio-temporal resolved virus replication dynamics simulations based on partial differential equations models (PDE) and evaluated with advanced numerical mathematical methods on leading supercomputers. This study presents an advanced highly nonlinear model of the genome replication cycle of a specific RNA virus, the Hepatitis C virus (HCV). The diffusion-reaction model mimics the interplay of the major components of the viral RNA (vRNA) cycle, namely non structural viral proteins (NSP), vRNA and a generic host factor. Technically, we couple surface PDEs (sufPDEs) on the 3D embedded 2D Endoplasmatic Reticulum (ER) manifold with PDEs in the 3D membranous web (MW) and cytosol volume. (The MWs are the replication factories growing on the ER induced by NSPs.) The sufPDE/PDE model is evaluated at realistic reconstructed cell geometries which are based on experimental data. The simulations couple the effects of NSPs which are restricted to the ER surface with effects appearing in the volume. The volume effects include the host factor supply from the cytosol and the MW dynamics. Special emphasis is put to the exchange of components between ER surface, MWs and cytosol volume. As the vRNA spatial properties are not fully understood so far in experiment, the model allows for vRNA both restricted to the ER and moving in the cytosol. The visualization of the simulation resembles a look into some sort of fully 3D resolved “in silico microscopes” to mirror and complement in vitro / in vivo experiments for the intracellular vRNA cycle dynamics. The output data are quantitatively consistent with experimental data and provoke advanced experimental studies to validate the model.

Manganese sludge, an industrial waste in the ferroalloy industry, contains various components and holds significant importance for sustainable development through its valorization. This study focuses on characterizing a manganese sludge and investigating its behavior during sulfuric acid leaching. The influence of process conditions, including temperature, acid concentration, liquid to solid ratio, and leaching duration, was examined. The results revealed that Mn, Zn, and K are the main leachable components, and their leaching rates increase with increasing temperature, liquid to solid ratio, and time. However, acid concentration requires optimization. High leaching rates of 90% for Mn, 90% for Zn, and 100% for K were achieved. Moreover, it was found that Pb in the sludge is converted to sulfate during the leaching which yields a sulfate concentrate rich in PbSO4. The leaching process for Mn and Zn species appears to follow a second or -third order reaction, and the calculation of rate constants indicated that Mn leaching kinetics are two to five times higher than those for Zn. Thermodynamic calculations were employed to evaluate the main chemical reactions occurring during leaching.

Cladding is typically used to protect components from wear and corrosion while also improving the aesthetic value and reliability of the substrate. The cladding process induces significant residual stresses due to the temperature difference between the substrate and the clad layer. However, these residual stresses could be effectively utilized by modifying processes and geometrical parameters. This paper introduces a novel methodology for using the weld-cladding process as a cost-effective alternative to various existing reinforcement techniques. The numerical analyses are performed to maximize the reinforcement of a cylindrical tool. The investigation of how the weld cladding develops compressive stresses on the specimen in response to a change in the weld beads and the welding sequence is presented. For the benchmark shape, experimental verification of the numerical model is performed. The impact of the distance between the weld beads and the effect of the tool diameter is numerically investigated. Furthermore, the variation in compressive stresses due to temperature fluctuations during the extrusion process has been evaluated. The results showed that adequate compressive stresses are generated on the welded parts through the cladding process after cooling. Hence, the targeted reinforcement of the substrate can be achieved by optimizing the welding sequence and process parameters.

Plants have acquired sets of highly regulated and complex signaling pathways to respond to unfavorable environmental conditions during evolution. Calcium signaling, as a vital mechanism, enables plants to respond to external stimuli, including abiotic and biotic stresses, and coordinate the basic processes of the growth and development. In the present study, the calcium sensor families, including CBL and CIPK, were investigated in the halophyte plant, Aeluropus littoralis, with a comprehensive analysis. Here, six AlCBL genes, and twenty AlCIPK genes were presented. The analysis of the gene structure and conserved motifs, as well as physicochemical properties, showed that these genes are highly conserved during evolution. The expression levels of AlCBL genes and AlCIPK genes were evaluated under salt stress in leaf and root tissue. Based on the real-time RT-PCR results, AlCIPK gene family had a higher variation in mRNA abundance compared to the AlCBL gene family. The AlCIPKs were found to have a higher abundance in leaves than in roots. The results suggest that the interaction pattern of AlCBL genes with AlCIPK is tissue-specific, and different interactions can be expected in leaves and roots. Based on these patterns AlCIPK3.1 - AlCBL4.1 and AlCIPK1.2 - AlCBL4.4 can interact in root tissue, while the AlCBL10 has the potential to interact with the AlCIPK5, AlCIPK26 and AlCIPK12.3 in the leaf tissue. These findings provide valuable information on the structure and function of calcium sensor families in Aeluropus littoralis a halophyte plant, for future research on the biological function of CBLs and CIPKs on salt stress resistance.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

Dendritic spines are essential for synaptic function because they constitute the neurons' postsynaptic compartment that receives the most excitatory input. The extracellularly shorter variant of the presynaptic cell adhesion molecules neurexins, β-neurexins, has been implicated in various aspects of synapse function including neurotransmitter release. However, its role in developing or stabilizing dendritic spines as fundamental computational units of excitatory synapses remained unclear. Here, we show by morphological analysis that the deletion of β-neurexins in hippocampal neurons in vitro and in hippocampal tissue in vivo affects presynaptic dense-core vesicles and, unexpectedly, postsynaptic spine structure. Specifically, we observed that the absence of β-neurexins led to an increase in longer spinous protrusions in vitro and more mature mushroom-type spines in the CA1 region of adult knockout mice. In addition, deletion of β-neurexins caused alterations in spine head dimension and more spines with perforations of their postsynaptic density but no change in the overall number of spines or synapses. Our results indicate that presynaptic β-neurexins play a role across the synaptic cleft, possibly by aligning with postsynaptic binding partners and glutamate receptors via transsynaptic columns.

Hybridization is recognized as a notable driver of evolution and adaptation, which closely related species may exploit in the form incomplete reproductive barriers. Three closely related species of Ceratocystis (i.e., C. fimbriata, C. manginecans and C. eucalypticola) previously have been shown to hybridize by mating naturally occurring self-sterile strains with an unusual laboratory-generated sterile isolate type, which could have impacted conclusions regarding the prevalence of hybridization and inheritance of mitochondria. In the current study we investigated whether interspecific crosses between fertile isolates of these three species are possible, and if so how mitochondria are inherited by the progeny. For this purpose, a PCR-RFLP method and a mitochondrial DNA-specific PCR technique were custom-made and applied in a novel approach of typing complete ascospore drops collected from the fruiting bodies in each cross to distinguish between self-fertilizations and potential hybridization. These markers showed hybridization between C. fimbriata and C. eucalypticola and between C. fimbriata and C. manginecans, while no hybridization was detected in the crosses involving C. manginecans and C. eucalypticola. In both sets of hybrid progeny, we detected biparental inheritance of mitochondria. This study was the first to successfully produce hybrids from a cross involving self-fertile isolates of Ceratocystis, and also provided the first direct evidence of biparental mitochondrial inheritance in the Ceratocystidaceae. This work lays the foundation for further research focused on investigating the role of hybridization in the speciation of Ceratocystis species, and if mitochondrial conflict could have influenced the process.

The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection and disease process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections, as well as influenza A infections and cytokine release syndrome (CRS) triggered by bacterial or viral infections. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease process in common skin disorders, such as psoriasis and atopic dermatitis, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

In power systems, flow allocation (FA) methods allow to allocate usage and costs of the transmission grid to each single market participant. Based on predefined assumptions, the power flow is split into isolated generator specific or producer specific sub-flows. Two prominent FA methods, Marginal Participation (MP) and Equivalent Bilateral Exchanges (EBE), build upon the linearized power flow and thus on the Power Transfer Distribution Factors (PTDF). Despite their intuitive and computationally efficient concept, they are restricted to networks with \emph{passive} transmission elements only. As soon as a significant number of \emph{controllable} transmission elements, such as High-voltage direct current (HVDC) lines, operate in the system, they loose their applicability. This work reformulates the two methods in terms of Virtual Injection Patters (VIP) which allows to efficiently introduce a shift parameter $q$, tuning contributions of net sources and net sinks in the network. Major properties and differences of the methods are pointed out. Finally, it is shown how the MA and EBE algorithm can be applied to generic meshed AC-DC electricity grids: Introducing a \emph{pseudo-impedance} which reflects the operational state of controllable elements, allows to extend the PTDF matrix under the assumption of knowing the current system's flow. Basic properties from graph theory are used for solving the pseudo-impedance dependent on the position in the network. This directly enables \emph{e.g.} HVDC lines to be considered in the MP and EBE algorithm. The extended methods are applied to a low-carbon European network model (PyPSA-EUR) with a spatial resolution of N=181 and an 18\% transmission expansion. The allocations of VIP and MP, show that countries with high wind potentials profit most from the transmission grid expansion. Based on the average usage of transmission system expansion a method of distributing operational and capital expenditures is proposed. Further it is shown, how injections from renewable resources strongly drive country-to-country allocations and thus cross-border electricity flows.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

Energy system optimization models (ESOM) are widely used to inform about energy transition strategies. The heterogeneity of consumers, especially in the heat sector, is rarely considered in these model types. Integrating consumer heterogeneity and behavioral factors into ESOMs may generate new insights for energy policy. In this study a literature review was conducted, identifying empirical data on consumer behavior for adopting residential heating systems. This data was integrated into an ESOM for the German heat sector, combining established methods for integrating consumer heterogeneity and a novel approach for calculating indirect costs, representing behavioral factors. The incorporation of consumer choice leads to a higher diversity in technology market shares in a business as usual and an ambitious measures scenario. Especially, the future role of log wood technologies in the private household sector may have been underestimated in previous studies and should be discussed, when designing policies. Still, these findings need to be handled with care, since the empirical data basis and the methodological basis is limited.

Membrane-coupled RNA transport is an emerging theme in fungal biology. This review focuses on the RNA cargo and mechanistic details of transport via two inter-related sets of organelles: endosomes and extracellular vesicles for intra- and intercellular RNA transfer. Simultaneous transport and translation of messenger RNAs (mRNAs) on the surface of shuttling endosomes is a conserved process pertinent to highly polarised eukaryotic cells, such as hyphae or neurons. Here we detail the endosomal mRNA transport machinery components and mRNA targets of the core RNA-binding protein Rrm4. Extracellular vesicles (EVs) are newly garnering interest as mediators of intercellular communication, especially between pathogenic fungi and their hosts. Landmark studies in plant-fungus interactions indicate EVs as a means of delivering various cargos, most notably small RNAs (sRNAs), for cross-kingdom RNA interference. Recent advances and implications of the nascent field of fungal EVs are discussed and potential links between endosomal and EV-mediated RNA transport are proposed.

Along with the rapid development of technology and industry, the need for energy storage has become fundamental. One promising energy storage devices is the supercapacitor. Several type supercapacitors are available, one of which is the electrical double-layer capacitor made from carbon graphite and multiwalled carbon nanotubes (MWCNTs). In this study, we combined these two materials into a working electrode in a three-electrode system. In the morphological analysis using scanning electron microscope, transmission electron microscope, and X-ray diffraction, the two materials were found to have formed a composite on the surface. In the electrochemical analysis, two types of testing were conducted using cyclic voltammetry and electrochemical impedance spectroscopy. Electrochemical analysis was carried out on five electrolyte concentrations of Na2SO4 from 1 to 6 M. The capacitance produced at concentrations of 1, 2, 3, 4, and 5 M were 34.395, 35.808, 46.284, 49.502, and 76.815 F/g, respectively. At an electrolyte concentration of 5 M Na2SO4, an energy density of 27.312 Wh/Kg and a power density of 343.786 W/Kg were produced. Meanwhile on concentration of 6 M, the surface of the electrode was damaged.

The acute phase protein Serum Amyloid A (SAA) is synthesised by the liver in response to inflammatory stimuli. Previous studies have revealed that SAA may be a better predictive marker for the course of inflammatory bowel disease (IBD) compared to C-reactive protein (CRP). Hence, this retrospective monocentric study evaluated whether SAA correlates with biomarkers like faecal calprotectin (FC), CRP, the Neutrophil to Lymphocyte ratio (NLR) and clinical disease activity of IBD patients. Serum samples from the IBD outpatient clinic of the University Hospital Heidelberg were analysed for their SAA concentrations if a FC concentration measurement was available from 14 days before or after collection of the serum sample. 306 serum samples from 265 patients (166 with Crohn’s disease, 91 with ulcerative colitis, 8 with IBD unclassified) met the inclusion criteria. There was a significant positive correlation between SAA and FC, CRP, the NLR and the Simple Clinical Colitis Activity Index. The cut-off for SAA serum concentration at 4.55 mg/l achieved a sensitivity of 57.5% and a specificity of 69.7% for the detection of active inflammation in IBD. SAA may be used as an additional biomarker in the disease monitoring strategy of IBD patients, especially in patients with low CRP concentrations.

We analyzed the peak spring tidal current speeds, annual mean tidal power densities (TPD) and annual energy production (AEP) obtained from experiment 06.1, referred as the "HYCOM model" throughout, of the three dimensional (3D), global model HYCOM in an area covering the Baja California Pacific and the Gulf of California. The HYCOM model is forced with astronomical tides and surface winds alone, and therefore is particularly suitable to assess the tidal current and wind-driven current contribution to in-stream energy resources. We find two areas within the Gulf of California, one in the Great Island Region and one in the Upper Gulf of California, where peak spring tidal flows reach speeds of 1.1 meters per second. Second to fifth-generation tidal stream devices would be suitable for deployment in these two areas, which are very similar in terms of tidal in-stream energy resources. However, they are also very different in terms of sediment type and range in water depth, posing different challenges for in-stream technologies. The highest mean TPD value when excluding TPDs equal or less than 50 W/m² (corresponding to the minimum velocity threshold for energy production) is of 172.8 W/m², and is found near the town of San Felipe, at (lat lon) = (31.006 -114.64); here energy would be produced during 39.00% of the time. Finally, wind-driven currents contribute very little to the mean TPD and the total AEP. Therefore, the device, the grid, and any energy storage plans need to take into account the periodic tidal current fluctuations, for optimal exploitation of the resources.

Introduction: Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. Materials and Methods Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10mg was administered intravenously 24 hours before surgery. Real-time intraoperative NIRF visualization was made with the SpectrumTM Fluorescence Imaging Camera System. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor as well as additional lesions, compared to preoperative MRI. PLC, liver metastases, and additional lesions were then resected according to oncological principles. Of all resected specimens the resection margins were analyzed with the fluorescence imaging system for ICG positive spots right after resection. Histology of additional detected lesions as well as ICG fluorescence compared to histological resection margins were assessed. Results Of the 66 included patients median age was 65.5 years (IQR 58.7 - 73.9), 27 (40.9%) were female and 18 (27.3%) were operated laparoscopically. Additional ICG positive lesions were detected in 23 (35.4%) patients of which nine (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to a ICG positive resection margin with a R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p=0.005). One and two year overall survival were 95.2% and 88.4%, respectively. Conclusion The here presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers a true potential to verify radical resection and improve patients´ outcome. Furthermore, implementation of NIRF guided imaging in liver tumor surgery allows to detect a considerable amount of additional malignant lesions.

The increasing prevalence of depression worldwide requires more effectiveness in therapy approaches and a molecular understanding of antidepressants mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze metabolomics data, univariate and multivariate analysis and biomarker capacity assessment using the classical receiver operating characteristic (ROC) curve were used. Support vector machine-linear kernel (SVM-LK), as a machine-learning algorithm was performed for binary classification. Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as potential markers. We identified 4 or 10 marker candidates with ROC curve greater than 0.9 for CSIS or fluoxetine effectiveness designation. SVM-LK has given accuracy of 61.50%, or 93.30%, and 7 or 25 predictive metabolites for CSIS vs. control and fluoxetine-treated CSIS vs. CSIS classification. Overall, metabolic fingerprints combined with ROC curve and SVM-LK may represent a new approach to identifying potential markers or predicting metabolites for group designation or classification.

The TanDEM-X mission is acquiring a new dataset to provide a temporally independent DEM, called "TanDEM-X Change DEM". This set of acquisitions taken between 2017 and 2020 has a clear temporal separation to the TanDEM-X global DEM data which were acquired between 2010 and 2015. Therefore, this new DEM aims to enable the characterization of terrain changes. Improvements in the acquisition planning and the data processing were necessary to generate this Change DEM with fewer acquisitions but still very high accuracy. For this, the use of an edited TanDEM-X DEM as a "starting point" for the interferometric processing is mandatory.

Introduction: Obstructive sleep apnea (OSA) is not only common in the general population but even more so in patients with tumors of the head and neck region. Untreated, it leads to reduced quality of life, increased daytime sleepiness, and other comorbidities. The aim of this study was to determine the difference in the occurrence of OSA in the patient population with head and neck tumors compared to the general population as represented by the Trend cohort of the Study of Health in Pomerania (SHIP) , and to assess the influence of tumor treatment. Methods: Between July 2018 and December 2021, preoperative polysomnography was conducted in 47 patients with histologically confirmed squamous cell carcinoma in the oropharynx, hypo-pharynx, or larynx. A follow-up polysomnography was performed in 23 patients 2-11 months af-ter completing treatment. The collected data was correlated with tumor treatment and tumor size. Results: Of the included patients, 43 were male and four were female. Age ranged from 54 to 90 years. The pretherapeutic measurement found no significant difference in the prevalence of a pathologically elevated apnea-hypopnea index (AHI) in our patients compared to the SHIP-Trend cohort. In the follow-up measurement after treatment completion, a significant deterioration in AHI was observed. Initially, 70 % of patients had an AHI > 5, after therapy this increased to 87 %. The effect was particularly pronounced in the group of patients with advanced tumor stages who had received primary chemoradiation. Conclusion: OSA is a relevant condition in patients with head and neck cancer. Tumor treatment can lead to an increased occurrence of sleep-related breathing disorders, especially in patients with advanced tumor stages undergoing primary chemoradiation. Additional studies are neces-sary to better understand the exact mechanism involved.

Among the thermophysical properties, the surface / interfacial tension, viscosity and density / molar volume of liquid alloys are the key properties for the modelling of microstructural evolution during solidification. Therefore, only reliable input data can yield accurate predictions preventing the error propagation in numerical simulations of solidification related processes. Due to experimental difficulties related to reactivity of metallic melts at high temperatures, the measured data are often unreliable or even lacking. The application of containerless processing techniques either leads to a significant improvement of the accuracy or makes the measurement possible at all. On the other side, accurate model predicted property values could be used to compensate the missing data; otherwise, the experimental data are useful for the validation of theoretical models. The choice of models is particularly important for the surface, transport and structural properties of liquid alloys representing the two limiting cases of mixing, i.e. ordered and phase separating alloy systems. To this aim, the thermophysical properties of the Fe-Si and Cu-Pb systems were analysed and the connections with the peculiarities of their mixing behaviours are highlighted.

Co-Zr amorphous alloys exhibit soft magnetic properties, whereas Co-rich crystalline magnetic phases in this alloy system display hard magnetic behaviour. In this study, an initial two-phase Co-Zr composite with an overall composition of 75 at.% Co and 25 at.% Zr was processed by high pressure torsion (HPT) and the effects of severe plastic deformation and subsequent thermal treatment on the structural evolution and its magnetic properties have been investigated. HPT processing allowed us to achieve an amorphous microstructure in the as-deformed state with low coercivity. To further tune magnetic properties and study the alloys’ crystallization behaviour, various annealed states are investigated. Microstructural properties are correlated to the magnetic properties and a decreasing coercivity with increasing annealing temperature is observed despite the onset of crystallization in the amorphous alloy. At higher annealing temperatures, coercivity increases again. The results appear promising to obtain tuneable rare-earth free magnetic materials by severe plastic deformation.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

Problem gambling among young people is an emerging trend globally. The online environment in particular offers various possibilities for gambling engagement. This is the first cross-national survey study using the social ecological model to analyze problem gambling, especially in the online context. The aim was to analyze how different social ecological spheres explain problem gambling. Participants were young people aged 15–25 in the United States (n = 1,212), South Korea (n = 1,192), Spain (n = 1,212), and Finland (n = 1,200). The South Oaks Gambling Screen (SOGS) instrument was used as a measure for problem gambling. Regression models predicted problem gambling with measures of intrapersonal, interpersonal, organizational, and societal spheres. Spanish participants had the highest SOGS score for problem gambling. Out of the spheres, organizational-sphere measures best explained the variation in problem gambling in all countries (26%) when compared to the societal (3%), interpersonal (5%) and intrapersonal (11%) spheres. In the full model, organizational-sphere measures had strong associations with problem gambling. These included consumer debt, online gambling community participation, online casino participation, and exposure to online pop-up advertisements. Other robust predictors of problem gambling included conformity to group norms in the interpersonal sphere and male gender and impulsivity in the intrapersonal sphere. Cross-national results were similar in different countries. The online context plays a major role in problem gambling behavior. The social ecological model is a useful tool by which to tackle problem gambling and develop preventative measures.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

The thorough description of the peculiarities of additively manufactured structures represents a current challenge for aspiring freeform fabrication methods, such as the selective laser melting (SLM). All of which have an immense advantage in the fast fabrication (no special tooling or moulds required), the geometrical flexibility in the design of components, and their efficiency when only low quantities are required. However, designs demand the precise knowledge of the material properties, which in case of additively manufactured structures are anisotropic and, under certain circumstances, in addition of an inhomogeneous nature. Furthermore, these characteristics are highly dependent on the fabrication settings. Within this study, the anisotropic tensile properties of selective laser melted stainless steel (1.4404, 316L) are investigated: The Young’s modulus ranged from 148 GPa to 227 GPa, the ultimate tensile strength from 512 MPa to 699 MPa and the breaking elongation ranged, respectively, from 12% to 43%. The results were compared to related studies, in order to classify the influence of the fabrication settings. Furthermore, the influence of the chosen raw material was addressed by comparing deviations on the directional dependencies reasoned by differing microstructural developments during manufacture. Stainless steel was found to possess its maximum strength at a 45° layer versus loading offset, which is precisely where AlSi10Mg was previously reported to be at its weakest.

Fe[C5H5N]2[N(CN)2]2 (1) was synthesized from a reaction of stoichiometric amounts of NaN(CN)2 and FeCl2·4 H2O in a methanol/pyridine solution. Single-crystal and powder diffraction show that 1 crystallizes in the monoclinic space group I2/m (no. 12), different from Mn[C5H5N]2[N(CN)2]2 (P21/c, no. 14) due to tilted pyridine rings, with a = 7.453(7) Å, b = 13.167(13) Å, c = 8.522(6) Å, β = 114.98(6)° and Z = 2. ATR-IR, AAS, and CHN measurements confirm the presence of dicyanamide and pyridine. Thermogravimetric analysis shows that π-stacking interactions of the pyridine rings play an important role in structural stabilization. Based on DFT-optimized structures, a chemical bonding analysis was performed using a local-orbital framework by projection from a plane-wave basis. The resulting bond orders and atomic charges are in good agreement with the expectations based on the structure analysis. SQUID magnetic susceptibility measurements show a high-spin state FeII compound with predominantly antiferromagnetic exchange interactions at lower temperatures.

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds.

Presynaptic Ca²⁺-influx through voltage-gated Ca²⁺ channels (VGCC) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca²⁺-influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca²⁺-indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca²⁺-transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca²⁺-influx but increased Ca²⁺-influx via N-type VGCCs. Moreover, we tested whether the decrease of Ca²⁺-influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease of presynaptic Ca²⁺-transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca²⁺-influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs.

To ensure high-quality care, operationalize resilience and fill the knowledge gap regarding how to improve the prerequisites for resilient performance, it is necessary to understand how adaptive capacity unfolds in practice. Coronavirus 2019 stress-tested complex healthcare systems, and intensive care was driven to an unprecedented escalation. The main aim of this research was to explain the escalation process of intensive care from a microlevel perspective, including expressions of resilient performance, intervening conditions at the micro-meso-macrolevels and short- and long-term consequences. A secondary aim was to provide clinical recommendations regarding how to optimize the prerequisites for resilient performance in intensive care. A grounded theory methodology was used. First-person stories from different healthcare professionals (n70) in two Swedish regions were analyzed using the constant comparative method. A novel conceptual model of the escalation process of intensive care emerged, and 41 clinical recommendations concerning the optimal prerequisites for resilient performance were identified. Escalation was conceptualized as a transition from threatening chaos to temporary order through a complex process of adaptation. To prepare for the future, the components space, stuff, staff, system and science with associated continuity plans must be implemented, anchored and communicated to actors at all levels of the system.

While many in-steam tidal energy resource studies have been carried out globally, very few studies have assessed the effect of seabed changes on tidal energy resources. For coastal regions in particular, where the seabed is generally more mobile than in deep waters, bathymetric evolution could have a significant effect on tidal energy production. Here two high-resolution models, one purely hydrodynamic and one morphodynamic, are used to analyse the potential effect of natural morphodynamic evolution on tidal energy resources at two macro-tidal sandy bays, Adaír Bay and San Jorge Bay, in the Upper Gulf of California, Mexico. The high-resolution models are validated using a low-resolution model and ADCP observations to assess the agreement between model predictions and observations of tides at three ADCP moorings within the domain of interest. The models’ skill is evaluated using several error statistics such as the mean relative error, the root mean square error (RMSE), and the correlation coefficient. It was found that the regions with the largest bed changes, and also the largest renewable energy resources, were near the shore. Moreover, the results indicated a good correlation between a) regions with the most significant depth changes, and b) the regions where the difference in annual energy production with and without depth change was largest. Finally, the morphodynamic model was run for two years, and the evolution of a zonal profile (in the west-east direction) off the coast at the southeastern corner of Adaír Bay was inspected. This profile evolved towards a featureless equilibrium profile, in good agreement with the morphological classification for macro-tidal sandy environments and with the model assumptions. But most importantly, this natural evolution would not be detrimental to tidal energy exploitation at the site.

The oil and gas industry faces increasing pressure to remove people from dangerous offshore environments. Robots present a cost-effective and safe method for inspection, repair and maintenance of topside and marine offshore infrastructure. In this work, we introduce a new immobile multi-sensing robot, the Limpet, which is designed to be low-cost and highly manufacturable, and thus can be deployed in huge collectives for monitoring offshore platforms. The Limpet can be considered an instrument, where in abstract terms, an instrument is a device that transforms a physical variable of interest (measurand) into a form that is suitable for recording (measurement). The Limpet is designed to be part of the ORCA (Offshore Robotics for Certification of Assets) Hub System, which consists of the offshore assets and all the robots (UAVs, drones, mobile legged robots etc.) interacting with them. The Limpet comprises the sensing aspect of the ORCA Hub System. We integrated the Limpet with Robot Operating System (ROS), which allows it to interact with other robots in the ORCA Hub System. In this work, we demonstrate how the Limpet can be used to achieve real-time condition monitoring for offshore structures, by combining remote sensing with signal processing techniques. We show an example of this approach for monitoring offshore wind turbines. We demonstrate the use of four different communication systems (WiFi, serial, LoRa and optical communication) for the condition monitoring process. By processing the sensor data on-board, we reduce the information density of our transmissions, which allows us to substitute short-range high-bandwidth communication systems with low-bandwidth long-range communication systems. We train our classifier offline and transfer its parameters to the Limpet for online classification, where it makes an autonomous decision based on the condition of the monitored structure.

Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintained and reinforced their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.

The limitations of investment casting of cobalt-based alloys are claimed to be less problematic with significant improvements in metal additive manufacturing by selective laser melting (SLM). Despite these advantages, the metallic devices are likely to display mechanical anisotropy in relation to build orientations, which could consequently affect their performance ‘in vivo’. In addition, there are inconclusive evidence concerning the requisite composition and post-processing steps (e.g. heat-treatment to relieve stress) that must be completed prior to the devices being used. In the current paper, we evaluate the microstructure of ternary cobalt-chromium-molybdenum (Co-Cr-Mo) and cobalt-chromium-tungsten (Co-Cr-W) alloys built with Direct Metal Printing and LaserCUSING SLM systems respectively at 0°, 30°, 60° and 90° inclinations (Φ) in as-built (AB) and heat-treated (HT) conditions. The study also examines the tensile properties (Young's modulus, E; yield strength, R_P0.2; elongation at failure, A_t and ultimate tensile strength, R_m), relative density (RD), and micro-hardness (HV5) and macro-hardness (HV20) as relevant physico-mechanical properties of the alloys. Data obtained indicate improved tensile properties and HV values after short and cost-effective heat-treatment cycle of Co-Cr-Mo alloy; however, the process did not homogenize the microstructure of the alloy. Annealing heat-treatment of Co-Cr-W led to significant isotropic characteristics with increased E and A_t (except for Φ = 90º) in contrast to decreased R_P0.2, R_m and HV values, compared to the AB form. Similarly, the interlaced weld-bead structures in AB Co-Cr-W were removed during heat-treatment, which led to a complete recrystallization in the microstructure. Both alloys exhibited defect-free microstructures with RD exceeding 99.5%.

Access and Benefit Sharing (ABS) is a framework which refers to a relatively recent type of legal requirements for access to and/or use of “genetic resources”. They are based on diverse national and regional laws and regulations, which mostly result from the implementation of the United Nations’ Convention on Biological Diversity (CBD) and its supplementary agreement, the Nagoya Protocol. Their ambition is to achieve fair and equitable sharing of benefits arising out of the use of genetic resources as an incentive to conserve and sustainably use them. This paper describes the experiences, practical constraints and complexities encountered by users of genetic resources when dealing with ABS legislation, with a focus on users from the private sector. We provide insights on how ABS laws have fundamentally changed the way of working with genetic resources in the hope that it inspires re-thinking of the ABS framework, to better support the overall objectives of the CBD.

Abstract: Mast cell (MC) specific proteases are of particular interest for space biology and medicine due to their biological activity in regulating targets of a specific tissue microenvironment. MC tryptase and chymase obtain the ability to remodel connective tissue through direct and indirect mechanisms. Yet, MC specific protease expression under space flight conditions has not been adequately investigated. Using immunohistochemical stainings, we analyzed in this study the protease profile of the jejunal, gastric and hepatic MC populations in three groups of Mongolian gerbils - vivarium control, synchronous experiment, and 12-day orbital flight on the Foton-M3 spacecraft, - and in two groups - vivarium control and anti-orthostatic suspension - included in the experiment simulating effects of weightlessness in the ground-based conditions. After a space flight, there was a decreased number of MCs in the studied organs combined with an increased proportion of chymase-positive MCs and MCs with a simultaneous content of tryptase and chymase; the secretion of specific proteases into the extracellular matrix increased. These changes in the expression of proteases were observed both in the mucosal and connective tissue MC subpopulations of the stomach and jejunum. Notably, the relative content of tryptase-positive MCs in the studied organs of the digestive system decreased. Space flight conditions simulated in the synchronous experiment caused no similar significant changes in the protease profile of MC populations. The space flight conditions resulted in an increased chymase expression combined with a decreased total number of protease-positive MCs apparently due to participating in the processes of extracellular matrix remodeling and regulating the state of the cardiovascular system.

Background and aims Loneliness and a low sense of mastery have been associated with excessive gambling, but the underlying processes of these relationships remain unstudied. Because psychological distress can increase vulnerability to excessive gambling, we investigated its mediating role in these relationships among young people. To meet the need for cross-country research, we also observed how these relationships occur in four countries with different cultures. Design, setting and participants Demographically balanced cross-sectional survey data were collected for 15–25-year-olds in Finland (n=1200; 50% male), the United States (n=1212; 49.8% male), South Korea (n=1192; 49.6% male) and Spain (n=1212; 51.2% male). Measurements Excessive gambling was measured with the South Oaks Gambling Screen, psychological distress was assessed with the 12-Item General Health Questionnaire, loneliness was measured with the Three-Item Loneliness Scale and low sense of mastery was assessed with the Pearlin Mastery Scale. Associations were examined first using zero-inflated negative binomial regression analyses with excessive gambling as the outcome. In addition, path analyses were performed to study how loneliness and low sense of mastery relate to excessive gambling, with psychological distress as the mediating variable. Findings Loneliness and low sense of mastery were associated indirectly with excessive gambling via psychological distress in all country samples. Low sense of mastery was also directly associated with excessive gambling. There was a direct association between loneliness and excessive gambling only in samples from South Korea and Spain. Conclusions Psychological distress is an important factor in understanding how loneliness and sense of mastery relate to gambling.

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

Dioclea apurensis Kunth is native to ferruginous rocky outcrops (known as canga) in the eastern Amazon. Native cangas are considered hotspots of biological diversity and have one of the largest iron ore deposits in the world. There, D. apurensis can grow in post-mining areas where molecular mechanisms and rhizospheric interactions with soil microorganisms are expected to contribute to their establishment in rehabilitating minelands. In this study, we compare the root proteomic profile and rhizosphere-associated bacterial and fungal communities of D. apurensis growing in canga and a rehabilitating mineland to characterize the main mechanisms that allow the growth and establishment in post-mining areas. The results showed that proteins involved in response to oxidative stress, drought, excess of iron, and phosphorus deficiency were more accumulated in canga and, therefore, helped explain its high establishment rates in rehabilitating minelands. Rhizospheric selectivity of microorganisms was more evident in canga. The microbial community structure was mostly different between the two habitats, denoting that despite having its preferences, D. apurensis can associate with beneficial soil microorganisms without specificity. Therefore, its good performance in rehabilitating minelands can also be improved or attributed to its ability to cope with beneficial soil-borne microorganisms. Native plants with such adaptations must be used to enhance the rehabilitation process.

A large variety of fermentation products are used in food and feed production, but also in other industries, and many of these products are produced with genetically modified microorganisms (GMMs). In food and feed production, prominent examples are amino acids, vitamins, food and feed enzymes, colorants, non-caloric sweeteners and human milk oligosaccharides. From a regulatory perspective, fermentation products are typically produced under containment. This means that premises, equipment and work processes need to be designed to prevent or at least minimize release of GMMs into the environment. The fermentation products themselves should not contain any live cells of the GMM. Over the past years, there have been concerning developments, particularly in the European Union, stipulating that also absence of recombinant DNA might be interpreted as a regulatory requirement for fermentation products produced with GMMs. In this paper, we (i) attempt to place these developments into the historical context, (ii) sketch the potential negative repercussions for the food and feed industries, (iii) elaborate on the safety of recombinant DNA, and (iv) postulate that recombinant DNA should remain an integral part of the safety assessment of fermentation products but should not be misconstrued as a criterion for regulatory classification of products of biotechnology.

Remote sensing technologies may play a fundamental role in the environmental assessment of open-cast mining and the accurate quantification of mine land rehabilitation efforts. Here, we developed a systematic geographic object-based image analysis (GEOBIA) approach to map the amount of revegetated area and to quantify the land-use changes in open-cast mines in the Carajás region situated in the eastern Amazon. Based on high-resolution satellite images from 2011 to 2015 from different sensors (GeoEye, WorldView-3 and Ikonos), we quantified forests, cangas (natural metalliferous savanna ecosystems), mine land, revegetated areas and water bodies. Based on the GEOBIA approach, threshold values were established to discriminate land cover classes using spectral bands, and the NDVI and NDWI indices and LiDAR digital ground and slope models. The overall accuracy was higher than 90%, and the Kappa indices varied between 0.82 and 0.88. During the observation period, the mining complex expanded; for that, canga and forest vegetation was converted to mine land. At the same time, the amount of revegetated area increased. Thus, we conclude that our approach is capable of providing consistent information regarding land cover changes in mines, with a special focus on the amount of revegetation necessary to fulfill environmental liabilities.

Direct Behavior Rating (DBR) as a behavioral progress monitoring tool can be designed as longitudinal assessment with only short intervals between measurement points. The reliability of these instruments has been evaluated mostly in observational studies with small samples based on generalizability theory. However, for standardized use in the pedagogical field, a larger and broader sample is required in order to assess measurement invariance between different participant groups and over time. Therefore, we constructed a DBR with multiple items to measure the occurrence of specific externalizing and internalizing student classroom behaviors on a Likert scale (1 = never to 7 = always). In a pilot study, two trained raters observed 16 primary school students and rated the student behavior over all items with a satisfactory reliability. In the main study, 108 regular primary school students, 97 regular secondary school students and 14 students in a clinical setting were rated daily over one week (five measurement points). IRT analyses confirmed the instrument’s technical adequacy, and latent growth models demonstrated the instrument’s stability over time. Further development of the instrument and study designs to implement DBRs are discussed.

This review systematically examines the multifaceted relationship between the tumor microenvironment, stromal interactions, and colorectal cancer (CRC) progression and metastasis. The analysis begins by assessing the gut microbiome's influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. In summary, this review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor-stroma interactions.

Recessive dystrophic epidermolysis (RDEB) is a rare, inherited and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.

Quantitative polymerase chain reaction (qPCR) has emerged as an important bioanalytical method for assessing the pharmacokinetics of human cell-based medicinal products after xenotransplantation into immunodeficient mice. A particular challenge in bioanalytical qPCR studies is that the different tissues of the host organism can affect amplification efficiency and amplicon detection to varying degrees, and ignoring these matrix effects can easily cause a significant underestimation of the true number of target cells in a sample. Here we describe the development and drug regulatory-compliant validation of a TaqMan® qPCR assay for quantification of mesenchymal stromal cells in the range of 125 to 20,000 cells/200 µl lysate by amplification of a human-specific, highly repetitive αsatellite DNA sequence of the chromosome 17 centromere region HSSATA17. Assessment of matrix effects in 14 different mouse tissues and blood revealed a wide range of spike recovery rates across the different tissue types from 11 to 174%. Based on these observations, we propose to perform systematic spike-and-recovery experiments during assay validation and to correct for the effects of the different tissue matrices on cell quantification in subsequent bioanalytical studies by multiplying the back-calculated cell number by tissue-specific factors derived from the inverse of the validated percent recovery rate.

In post mortem analyses, SARS-CoV-2 was found in the middle ear of some, but not all patients with COVID-19 disease. It is not clear whether SARS-CoV-2 penetrated the ear passively post mortem, or existed in the middle ear of living patients during, and perhaps also after infection. This study investigates whether SARS-CoV-2 can be found in the middle ear of living patients during ear surgery. Swabs from the nasopharynx, the filter connected to the tracheal tube and secretion from the middle ear were collected during middle ear surgery. All samples were tested for the presence of SARS-CoV-2 with PCR. History of vaccination, COVID-19 and contact with SARS-CoV-2-positive individuals were recorded preoperatively. Postoperative SARS-CoV-2 infection was noted at the follow-up visit. Overall 63 participants (62%) were children and 39 (38%) were adults. SARS-CoV-2 was found in the middle ear and in the nasopharynx of two and four CovEar Study participants, respectively. The filter connected to the tracheal tube was sterile in all cases. Cycle threshold (ct) values of the PCR test were between 25.94 and 37.06. SARS-CoV-2 penetrates into the middle ear of living patients and can be found in asymptomatic patients. The presence of SARS-CoV-2 in the middle ear may have implications for ear surgery and can pose a risk of infection for operating room staff. It may also directly affect the audio-vestibular system.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Terrestrial laser scanning (TLS) has been adopted as a feasible technique to digitize trees and forest stands, providing accurate information on tree and forest structural attributes. However, there is limited understanding on how a variety of forest structural changes can be quantified using TLS in boreal forest conditions. In this study, we assessed the accuracy and feasibility of TLS in quantifying changes in the structure of boreal forests. We collected TLS data and field reference from 37 sample plots in 2014 (T1) and 2019 (T2). Tree stems typically have planar, vertical, and cylindrical characteristics in a point cloud, and thus we applied surface normal filtering, point cloud clustering, and RANSAC-cylinder filtering to identify these geometries and to characterize trees and forest stands at both time points. The results strengthened the existing knowledge that TLS has the capacity to characterize trees and forest stands in space and showed that TLS could characterize structural changes in time in boreal forest conditions. Root-mean-square-errors (RMSEs) in the estimates for changes in the tree attributes were 0.99-1.22 cm for diameter at breast height (Δdbh), 44.14-55.49 cm2 for basal area (Δg), and 1.91-4.85 m for tree height (Δh). In general, tree attributes were estimated more accurately for Scots pine trees, followed by Norway spruce and broadleaved trees. At the forest stand level, an RMSE of 0.60-1.13 cm was recorded for changes in basal area-weighted mean diameter (ΔDg), 0.81-2.26 m for changes in basal area-weighted mean height (ΔHg), 1.40-2.34 m2/ha for changes in mean basal area (ΔG), and 74-193 n/ha for changes in the number of trees per hectare (ΔTPH). The plot-level accuracy was higher in Scots pine-dominated sample plots than in Norway spruce-dominated and mixed-species sample plots. TLS-derived tree and forest structural attributes at time points T1 and T2 differed significantly from each other (p < 0.05). If there was an increase or decrease in dbh, g, h, height of the crown base, crown ratio, Dg, Hg, or G recorded in the field, a similar outcome was achieved by using TLS. Our results provided new information on the feasibility of TLS for the purposes of forest ecosystem growth monitoring.

Drought-induced plant mortality has increased globally during the last decades and is forecasted to influence global vegetation dynamics. Timely information on plant water dynamics is essential for understanding and anticipating drought-induced plant mortality. The most common metric that has been used for decades for measuring water stress is leaf water potential (Ψ_L), which is measured destructively. To obtain information on water dynamics from trees and forested landscapes, remote sensing methods have been developed. However, the spatial and temporal resolution of the existing methods have limited our understanding of water dynamics and diurnal variation of Ψ_L within single trees. Thus, we investigated the capability of terrestrial laser scanning (TLS) intensity in observing diurnal variation in Ψ_L during a 50 hour monitoring period and aimed to improve understanding on how large part of the diurnal variation in Ψ_L can be captured using intensity observations. We found that TLS intensity at 905 nm wavelength was able to explain 78% of the variation in Ψ_L for three trees of two tree species with a root-mean square error of 0.137 MPa. Based on our experiment with three trees, time-series of TLS intensity measurements can be used in detecting changes in Ψ_L, and thus it is worthwhile to expand the investigations to cover a wider range of tree species and forests and further increase our understanding of plant water dynamics at wider spatial and temporal scales.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.