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Background: Non-melanoma skin cancers (NMSCs) are responsible for up to one-third of all human malignancies. Surgery is usually the treatment of choice, but patients often experience pain during the procedure. Topical rhenium-188 resin skin cancer treatment (RSCT) may be a valid therapeutic alternative. Methods: In this monocentric pilot study, 19 patients suffering from NMSC were treated with RSCT. Most of these patients had also experienced surgery, either because they developed a new NMSC in aftercare, or they had suffered previously from NMSC. Three RSCT-treated patients, who had no exposure to surgery so far, were paired with three matched patients, who had received surgery. We sought to evaluate and compare the patients’ experience with both treatments. A questionnaire assessed patients’ perceptions regarding side effects, aesthetic outcomes, wound care, fear of complications, and personal treatment preferences. Patients evaluated the different parameters of their either RSCT- or surgery-treated lesions on a scale from 0–10. Results: Patients were more afraid of complications before surgery than before RSCT (p = 0.04). Treatment with RSCT caused significantly less pain on treatment day (mean 0.56) than surgery (mean 2.32) (0 no pain, 10 maximum pain) (p = 0.02) and 14 days after the procedure (mean 0.89 versus mean 2.47) (p = 0.02). On day 14, RSCT-treated lesions were also significantly less itchy (mean 0.34) than after surgery (mean 1.50). Most patients were very satisfied with the aesthetic outcome after both RSCT (mean 8.42) and surgery (mean 8.31) (p = 0.89). In the case of a new NMSC, the majority of patients who experienced both treatments would rather be treated primarily with RSCT (44%) or would consider both options (31%); only 19% preferred surgery. Conclusion: Patients evaluated RSCT as less painful than surgery. The aesthetic outcomes of both treatments were comparable. For pain-sensitive patients, RSCT might be a preferable treatment option.

Background: Obesity during pregnancy is related to adverse maternal and neonatal outcomes. Factors involved in these outcomes may include increased maternal insulin resistance, inflammation, oxidative stress, and nutrient mishandling. The placenta is the primary determinant of fetal outcomes, and its function can be impacted by maternal obesity. The aim of this study on mice was to determine the effect of obesity on maternal lipid handling, inflammatory and redox state, and placental oxidative stress, inflammatory signaling, and gene expression relative to female and male fetal growth. Methods: Female mice were fed control or obesogenic high-fat/high-sugar diet (HFHS) from 9 weeks prior to, and during, pregnancy. On day 18.5 of pregnancy, maternal plasma, and liver, placenta, and fetal serum were collected to examine the immune and redox states. The placental labyrinth zone (Lz) was dissected for RNA-sequencing analysis of gene expression changes. Results: the HFHS diet induced, in the dams, hepatic steatosis, oxidative stress (reduced catalase, elevated protein oxidation) and the activation of pro-inflammatory pathways (p38-MAPK), along with imbalanced circulating cytokine concentrations (increased IL-6 and decreased IL-5 and IL-17A). HFHS fetuses were asymmetrically growth-restricted, showing sex-specific changes in circulating cytokines (GM-CSF, TNF-α, IL-6 and IFN-γ). The morphology of the placenta Lz was modified by an HFHS diet, in association with sex-specific alterations in the expression of genes and proteins implicated in oxidative stress, inflammation, and stress signaling. Placental gene expression changes were comparable to that seen in models of intrauterine inflammation and were related to a transcriptional network involving transcription factors, LYL1 and PLAG1. Conclusion: This study shows that fetal growth restriction with maternal obesity is related to elevated oxidative stress, inflammatory pathways, and sex-specific placental changes. Our data are important, given the marked consequences and the rising rates of obesity worldwide.

The present state of research in computational fluid dynamics (CFD) is marked by an ongoing process of refining numerical methods and algorithms with the goal of achieving accurate modeling and analysis of fluid flow and heat transfer phenomena. Remarkable progress has been achieved in the domains of turbulence modeling, parallel computing, and mesh generation, resulting in heightened simulation precision when it comes to capturing complex flow behaviors. Nevertheless, CFD faces a significant challenge due to the time and expertise needed for a meticulous simulation setup and intricate numerical techniques. To surmount this challenge, we introduce paint2sim—an innovative mobile application designed to enable on-the-fly 2D fluid simulations using a device’s camera. Seamlessly integrated with OpenLB, a high-performance Lattice Boltzmann-based library, paint2sim offers accurate simulations. The application leverages the capabilities of the Lattice Boltzmann Method (LBM) to model fluid behaviors accurately. Through a symbiotic interaction with the open-source OpenCV library, paint2sim can scan and extract hand-drawn simulation domains, affording the capability for instant simulation and visualization. Notably, paint2sim can also be regarded as a digital twin, facilitating just-in-time representation and analysis of 2D fluid systems. The implications of this technology extend significantly to both fluid dynamics education and industrial applications, effectively lowering barriers and rendering fluid simulations more accessible. Encouragingly, the outcomes of simulations conducted with paint2sim showcase promising qualitative and quantitative results. Overall, paint2sim offers a groundbreaking approach to mobile 2D fluid simulations, providing users with just-in-time visualization and accurate results, while simultaneously serving as a digital twin for fluid systems.

PIEZO1 is a mechanosensitive cation channel implicated in shear stress-mediated endothelial-dependent vasorelaxation. Since altered shear stress patterns induce a pro-inflammatory endothelial environment, we analyzed transcriptional profiles of human endothelial cells to determine the effect of altered shear stress patterns and subsequent prooxidant and inflammatory conditions on PIEZO1 and mechanosensitive-related genes (MRG). In silico analyses were validated in vitro by assessing PIEZO1 transcript levels in both the umbilical artery (HUAEC) and vein (HUVEC) endothelium. Transcriptional profiling showed that PIEZO1 and some MRG associated with the inflammatory response were upregulated in response to high (15 dyn/cm2) and extremely high shear stress (30 dyn/cm2) in HUVEC. Changes in PIEZO1 and inflammatory MRG were paralleled by p65 but not KLF or YAP1 transcription factors. Similarly, PIEZO1 transcript levels were upregulated by TNF-alpha (TNF-α) in diverse endothelial cell types, and pre-treatment with agents that prevent p65 translocation to the nucleus abolished PIEZO1 induction. ChIP-seq analysis revealed that p65 bonded to the PIEZO1 promoter region, an effect increased by the stimulation with TNF-α. Altogether this data showed that NF-kappa B activation via p65 signaling regulates PIEZO1 expression, providing a new molecular link for prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.

Wall-flow filters are applied in the exhaust treatment of internal combustion engines for the removal of particulate matter (PM). Over time, the pressure drop inside those filters increases due to the continuously introduced solid material, which forms PM deposition layers on the filter substrate. This leads to the necessity of regenerating the filter. During such a regeneration process, fragments of the PM layers can potentially rearrange inside single filter channels. This may lead to the formation of specific deposition patterns, which affect a filter’s pressure drop, its loading capacity and the separation efficiency. The dynamic formation process can still not consistently be attributed to specific influence factors, and appropriate calculation models that enable a quantification of respective factors do not exist. In the present work, the dynamic rearrangement process during the regeneration of a wall-flow filter channel is investigated. As a direct sequel to the investigation of a static deposition layer in a previous work, the present one additionally investigates the dynamic behaviour following the detachment of individual layer fragments as well as the formation of channel plugs. The goal of this work is the extension of the resolved particle methodology used in the previous work via a discrete method to treat particle–particle and particle–wall interactions in order to evaluate the influence of the deposition layer topology, PM properties and operating conditions on dynamic rearrangement events. It can be shown that a simple mean density methodology represents a reproducible way of determining a channel plug’s extent and its average density, which agrees well with values reported in literature. The sensitivities of relevant influence factors are revealed and their impact on the rearrangement process is quantified. This work contributes to the formulation of predictions on the formation of specific deposition patterns, which impact engine performance, fuel consumption and service life of wall-flow filters.

Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in Japan. It was first reported in humans in 2011 in Russia. It has subsequently been reported in North America, Europe, and Asia. B. miyamotoi infection is widespread in Ixodes ticks in the northeastern, northern Midwestern, and far western United States and in Canada. In endemic areas, human B. miyamotoi seroprevalence averages from 1 to 3% of the population, compared with 15 to 20% for B. burgdorferi. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Complications include relapsing fever and rarely, meningoencephalitis. Because clinical manifestations are nonspecific, diagnosis requires laboratory confirmation by PCR or blood smear examination. Antibiotics are effective in clearing infection and are the same as those used for Lyme disease, including doxycycline, tetracycline, erythromycin, penicillin, and ceftriaxone. Preventive measures include avoiding areas where B. miyamotoi-infected ticks are found, landscape management, and personal protective strategies such as protective clothing, use of acaricides, and tick checks with rapid removal of embedded ticks.

Rearrangement events in wall-flow filters lead to the formation of specific deposition patterns, which affect a filter’s pressure drop, its loading capacity and the separation efficiency. A universal and consistent formulation of probable causes and influence factors does not exist and appropriate calculation models that enable a quantification of respective influence factors are missing. In this work, a previously developed lattice Boltzmann method, which has been used with inflow velocities of up to 2 m s−1, is applied to elevated velocities of up to 60 m s−1. The particle-free flow, a single layer fragment and a deposition layer during break-up are investigated as three different scenarios. One goal of this work is a comprehensive quantification of the stability and accuracy of both particle-free and particle-including flows, considering static, impermeable deposition-layer fragments. A second goal is the determination of the hydrodynamic surface forces and the deduction of the local detachment likelihood of individual layer fragments. Satisfactory stability and accuracy can be shown for fluid velocity, fluid pressure and the hydrodynamic forces. When considering layer fragments, the parameter domain turns out to be limited to inflow velocities of 28 m s−1. It is shown that fragment detachment rather occurs consecutively and regions of no possible detachment are identified. The work contributes to an understanding of rearrangement events and respective deposition pattern predictions and enables potential optimizations in engine performance, fuel consumption and the service life of wall-flow filters.

Ever since the pioneering studies of George Mendenhall, Klaus Baltzer, Dennis McCarthy, and Moshe Weinfeld, the structural analogies between Deuteronomy and ancient Near Eastern treaties have been a key issue in the scholarly study of the book. More recently, the hypothesis that Deuteronomy 13* and 28* could even represent a Hebrew rendering of the Neo-Assyrian Succession Treaties of Esarhaddon has prompted a yet intensified investigation of the matter. Yielding nuanced models to account for the traditio-historical pluriformity of features in Deuteronomy vis-à-vis the various strands of tradition found in late Hittite and Neo-Assyrian, as well as Aramaic comparative evidence, this latter discussion has arguably once again broadened the horizon. In any case, it only emphasizes that reading Deuteronomy against the background of the ancient Near Eastern treaty tradition more broadly provides an indispensable perspective when it comes to the literary genesis of Deuteronomy as we have it. What is more, it also opens a window on its interpretation. At the same time, however, it can also lead to certain misconceptions, for as much as major parts of Deuteronomy are modeled on a treaty, Deuteronomy is no treaty. The comparative perspective thus requires one to heed both commonalities and differences. This article focuses on one such difference, namely the constellation of agents. It is typical of ancient Near Eastern treaties that the contracting parties agree to delegate the task of safeguarding the treaty to a third party constituted by deities. It is these gods who figure as “witnesses” of the curses that the contracting parties call upon themselves if they should act contrary to the treaty, the term “witness” also denoting, according to the semantics of ancient Near Eastern treaty discourse, “agent of the sanctions.” Hence, the agreed upon sanctions are conceived of as coming into effect without the further involvement of the contracting parties. In fact, this particular feature is the operating principle which makes an ancient Near Eastern treaty work. In Deuteronomy, however, it does not apply. While intriguingly enough there are certain entities in the close context of the curse sections which are called “witnesses,” none of them can truly figure as a witness in the sense described above, for none of them is a deity; neither is there an attempt made to charge these “witnesses” with putting into effect the curse sanctions. Often overlooked, this aspect has significant ramifications for the understanding of the curses in Deuteronomy and the treaty style structure in general.

Background: Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. Methods: Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. Results: Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. Conclusions: BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy.

The design and optimization of photobioreactor(s) (PBR) benefit from the development of robust and quantitatively accurate computational fluid dynamics (CFD) models, which incorporate the complex interplay of fundamental phenomena. In the present work, we propose a comprehensive computational model for tubular photobioreactors equipped with glass sponges. The simulation model requires a minimum of at least three submodels for hydrodynamics, light supply, and biomass kinetics, respectively. First, by modeling the hydrodynamics, the light–dark cycles can be detected and the mixing characteristics of the flow (besides the mass transport) can be analyzed. Second, the radiative transport model is deployed to predict the local light intensities according to the wavelength of the light and scattering characteristics of the culture. The third submodel implements the biomass growth kinetic by coupling the local light intensities to hydrodynamic information of the CO2 concentration, which allows to predict the algal growth. In combination, the novel mesoscopic simulation model is applied to a tubular PBR with transparent walls and an internal sponge structure. We showcase the coupled simulation results and validate specific submodel outcomes by comparing the experiments. The overall flow velocity, light distribution, and light intensities for individual algae trajectories are extracted and discussed. Conclusively, such insights into complex hydrodynamics and homogeneous illumination are very promising for CFD-based optimization of PBR.

Umbilical and placental vessels and endothelial cells (EC) are common models to study placental function and vascular programming. Arterio-venous differences are present in the umbilical endothelium; however, the heterogeneity of small placental vessels and the expression of potential micro- vs. macro-vascular (MMV) markers are poorly described. Here, we performed a meta-analysis of transcriptomic and DNA methylation data from placental and umbilical EC. Expression and methylation profiles were compared using hierarchical clustering, dimensionality reduction (i.e., tSNE, MDS, and PHATE), and enrichment analysis to determine the occurrence of arterio-venous (AVH) and micro-macro heterogeneity (MMH). CpG sites correlated with gene expression of transcriptional markers of MMH and AVH were selected by Lasso regression and used for EC discrimination. General transcriptional profile resulted in clear segregation of EC by their specific origin. MM and AVH grouping were also observed when microvascular markers were applied. Altogether, this meta-analysis provides cogent evidence regarding the transcriptional and epigenomic profiles that differentiate among EC, proposing novel markers to define phenotypes based on MM levels.

Estimating seabird and pinniped abundance is central to wildlife management and ecosystem monitoring in Antarctica. Unoccupied aerial systems (UAS) can collect images to support monitoring, but manual image analysis is often impractical. Automating target detection using deep learning techniques may improve data acquisition, but different image sensors may affect target detectability and model performance. We compared the performance of automated detection models based on infrared (IR) or color (RGB) images and tested whether IR images, or training data that included annotations of non-target features, improved model performance. For this assessment, we collected paired IR and RGB images of nesting penguins (Pygoscelis spp.) and aggregations of Antarctic fur seals (Arctocephalus gazella) with a small UAS at Cape Shirreff, Livingston Island (60.79 °W, 62.46 °S). We trained seven independent classification models using the Video and Image Analytics for Marine Environments (VIAME) software and created an open-access R tool, vvipr, to standardize the assessment of VIAME-based model performance. We found that the IR images and the addition of non-target annotations had no clear benefits for model performance given the available data. Nonetheless, the generally high performance of the penguin models provided encouraging results for further improving automated image analysis from UAS surveys.

Computational fluid dynamics (CFD) are being used more and more in the industry to understand and optimize processes such as fluid flows. At the same time, tools such as augmented reality (AR) are becoming increasingly important with the realization of Industry 5.0 to make data and processes more tangible. Placing the two together paves the way for a new method of active learning and also for an interesting and engaging way of presenting industry processes. It also enables students to reinforce their understanding of the fundamental concepts of fluid dynamics in an interactive way. However, this is not really being utilized yet. For this reason, in this paper, we aim to combine these two powerful tools. Furthermore, we present the framework of a modular open-source library for scientific visualization of fluid flow “OpenVisFlow” which simplifies the creation of such applications and enables seamless visualization without other software by allowing users to integrate the visualization step into the simulation code. Using this framework and the open-source extension AR-Core, we show how a new markerless visualization tool can be implemented.

In the original publication [...]

Wall-flow filters are a standard component in exhaust gas aftertreatment and have become indispensable in vehicles. Ash and soot particles generated during engine combustion are deposited in diesel or gasoline particulate filters. During regeneration, the soot particles are oxidized. The remaining ash particles can form different deposition patterns: a homogenous layer or plug-end filling. It has not yet been clarified whether the plug-end filling is first formed by rearrangements of agglomerates before and during the regeneration of the reactive particles. In this study, experiments are carried out with a single channel of a wall-flow filter. For the investigations, a layer of inert and reactive particles is formed. The rearrangement of agglomerates is achieved by flowing through the model filter channel and observed with a high-speed camera. The particulate structures detach at the channel inlet, are transported along the channel and deposited at the plug. The velocity of the detached agglomerates depends on their size, shape, track and the gas velocity in the channel. If the agglomerate is near the walls of the model filter channel, the gas velocity deviates from the gas velocity in the core flow. The higher the gas velocity, the higher the agglomerate velocity achieved and the larger the detached agglomerates.

As micromixers offer the cheap and simple mixing of fluids and suspensions, they have become a key device in microfluidics. Their mixing performance can be significantly increased by periodically varying the inlet pressure, which leads to a non-static flow and improved mixing process. In this work, a micromixer with a T-junction and a meandering channel is considered. A periodic pulse function for the inlet pressure is numerically optimized with regard to frequency, amplitude and shape. Thereunto, fluid flow and adsorptive concentration are simulated three-dimensionally with a lattice Boltzmann method (LBM) in OpenLB. Its implementation is then combined with forward automatic differentiation (AD), which allows for the generic application of fast gradient-based optimization schemes. The mixing quality is shown to be increased by 21.4% in comparison to the static, passive regime. Methodically, the results confirm the suitability of the combination of LBM and AD to solve process-scale optimization problems and the improved accuracy of AD over difference quotient approaches in this context.

Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson’s disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional crosstalk between dopaminergic interneurons and dopamine receptors (D2/D3R). In rats, hemiparkinsonism (hemi-PD) can be induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB), disrupting dopaminergic neurons of the substantia nigra pars compacta (SNpc). In a previous study, we showed that subsequent injection of botulinum neurotoxin-A (BoNT-A) into the striatum can reverse most of the pathological motor symptoms and normalize the D2/D3R availability. To determine whether this rat model is suitable to explain olfactory deficits that occur in humans with PD, we examined the availability of D2/D3R by longitudinal [18F]fallypride-PET/CT, the density of tyrosine hydroxylase immunoreactivity in the OB, olfactory performance by an orienting odor identification test adapted for rats, and a connectome analysis. PET/CT and immunohistochemical data remained largely unchanged after 6-OHDA lesion in experimental animals, suggesting that outcomes of the 6-OHDA hemi-PD rat model do not completely explain olfactory deficits in humans. However, after subsequent ipsilateral BoNT-A injection into the striatum, a significant 8.5% increase of the D2/D3R availability in the ipsilateral OB and concomitant improvement of olfactory performance were detectable. Based on tract-tracing meta-analysis, we speculate that this may be due to indirect connections between the striatum and the OB.

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease.

Babesia are tick-borne intra-erythrocytic parasites and the causative agents of babesiosis. Babesia, which are readily transfusion transmissible, gained recognition as a major risk to the blood supply, particularly in the United States (US), where Babesia microti is endemic. Many of those infected with Babesia remain asymptomatic and parasitemia may persist for months or even years following infection, such that seemingly healthy blood donors are unaware of their infection. By contrast, transfusion recipients are at high risk of severe babesiosis, accounting for the high morbidity and mortality (~19%) observed in transfusion-transmitted babesiosis (TTB). An increase in cases of tick-borne babesiosis and TTB prompted over a decade-long investment in blood donor surveillance, research, and assay development to quantify and contend with TTB. This culminated in the adoption of regional blood donor testing in the US. We describe the evolution of the response to TTB in the US and offer some insight into the risk of TTB in other countries. Not only has this response advanced blood safety, it has accelerated the development of novel serological and molecular assays that may be applied broadly, affording insight into the global epidemiology and immunopathogenesis of human babesiosis.

Learning content in mathematics, such as vector geometry, is still predominantly taught in an abstract manner, as the visualization and interaction of three-dimensional problems are limited with classical forms of teaching such as blackboard lessons or exercise sheets. This research article proposes the use of augmented reality (AR) in mathematics education. The proposed approach aims at easing the learning process related to vector geometry currently taught in senior mathematics classes by using intuitive visualization. The article introduces the concept of AR and presents the didactic foundations and the influence on the learning process based on an extensive literature review. Although studies see great potential in the use of AR for teaching mathematics, the method has so far hardly been used in schools. This can be mainly explained by the technological entry barrier of AR and the lack of simple, robust AR applications, in particular for vector geometry. To fill this gap, the authors developed “cleARmaths”, a developed android application for augmented reality-based teaching in vector geometry that allows widespread use. As a didactical concept, some example exercises sessions with the app are proposed, demonstrating how the app could be used in a mathematics classroom. Finally, the app was evaluated in a mathematics class and the results analyzed in a detailed study. It was found by the teacher and students to be beneficial and amusing, demonstrating the potential for AR in mathematics classes.

In this paper, we use a fluid–structure interaction (FSI) approach to simulate a Coriolis mass flowmeter (CMF). The fluid dynamics is calculated by the open-source framework OpenLB, based on the lattice Boltzmann method (LBM). For the structural dynamics we employ the open-source software Elmer, an implementation of the finite element method (FEM). A staggered coupling approach between the two software packages is presented. The finite element mesh is created by the mesh generator Gmsh to ensure a complete open source workflow. The Eigenmodes of the CMF, which are calculated by modal analysis, are compared with measurement data. Using the estimated excitation frequency, a fully coupled, partitioned, FSI simulation is applied to simulate the phase shift of the investigated CMF design. The calculated phase shift values are in good agreement to the measurement data and verify the suitability of the model to numerically describe the working principle of a CMF.

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

A detailed knowledge of the influence of a particle’s shape on its settling behavior is useful for the prediction and design of separation processes. Models in the available literature usually fit a given function to experimental data. In this work, a constructive and data-driven approach is presented to obtain new drag correlations. To date, the only considered shape parameters are derivatives of the axis lengths and the sphericity. This does not cover all relevant effects, since the process of settling for arbitrarily shaped particles is highly complex. This work extends the list of considered parameters by, e.g., convexity and roundness and evaluates the relevance of each. The aim is to find models describing the drag coefficient and settling velocity, based on this extended set of shape parameters. The data for the investigations are obtained by surface resolved simulations of superellipsoids, applying the homogenized lattice Boltzmann method. To closely study the influence of shape, the particles considered are equal in volume, and therefore cover a range of Reynolds numbers, limited to [9.64, 22.86]. Logistic and polynomial regressions are performed and the quality of the models is investigated with further statistical methods. In addition to the usually studied relation between drag coefficient and Reynolds number, the dependency of the terminal settling velocity on the shape parameters is also investigated. The found models are, with an adjusted coefficient of determination of 0.96 and 0.86, in good agreement with the data, yielding a mean deviation below 5.5% on the training and test dataset.

The simulation of surface resolved particles is a valuable tool to gain more insights in the behaviour of particulate flows in engineering processes. In this work the homogenized lattice Boltzmann method as one approach for such direct numerical simulations is revisited and validated for different scenarios. Those include a 3D case of a settling sphere for various Reynolds numbers. On the basis of this dynamic case, different algorithms for the calculation of the momentum exchange between fluid and particle are evaluated along with different forcing schemes. The result is an updated version of the method, which is in good agreement with the benchmark values based on simulations and experiments. The method is then applied for the investigation of the tubular pinch effect discovered by Segré and Silberberg and the simulation of hindered settling. For the latter, the computational domain is equipped with periodic boundaries for both fluid and particles. The results are compared to the model by Richardson and Zaki and are found to be in good agreement. As no explicit contact treatment is applied, this leads to the assumption of sufficient momentum transfer between particles via the surrounding fluid. The implementations are based on the open-source C++ lattice Boltzmann library OpenLB.

The industrial particle sensor market lacks simple, easy to use, low cost yet robust, safe and fast response solutions. Towards development of such a sensor, for in-line use in micro channels under continuous flow conditions, this work introduces static light scattering (SLS) determination of particle diameter using a laser with an emission power of less than 5 µW together with sensitive detectors with detection times of 1 ms. The measurements for the feasibility studies are made in an angular range between 20° and 160° in 2° increments. We focus on the range between 300 and 1000 nm, for applications in the production of paints, colors, pigments and crystallites. Due to the fast response time, reaction characteristics in microchannel designs for precipitation and crystallization processes can be studied. A novel method for particle diameter characterization is developed using the positions of maxima and minima and slope distribution. The novel algorithm to classify particle diameter is especially developed to be independent of dispersed phase concentration or concentration fluctuations like product flares or signal instability. Measurement signals are post processed and particle diameters are validated against Mie light scattering simulations. The design of a low cost instrument for industrial use is proposed.

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.

In this paper, we compare the capabilities of two open source near-wall-modeled large eddy simulation (NWM-LES) approaches regarding prediction accuracy, computational costs and ease of use to predict complex turbulent flows relevant to internal combustion (IC) engines. The applied open source tools are the commonly used OpenFOAM, based on the finite volume method (FVM), and OpenLB, an implementation of the lattice Boltzmann method (LBM). The near-wall region is modeled by the Musker equation coupled to a van Driest damped Smagorinsky-Lilly sub-grid scale model to decrease the required mesh resolution. The results of both frameworks are compared to a stationary engine flow bench experiment by means of particle image velocimetry (PIV). The validation covers a detailed error analysis using time-averaged and root mean square (RMS) velocity fields. Grid studies are performed to examine the performance of the two solvers. In addition, the differences in the processes of grid generation are highlighted. The performance results show that the OpenLB approach is on average 32 times faster than the OpenFOAM implementation for the tested configurations. This indicates the potential of LBM for the simulation of IC engine-relevant complex turbulent flows using NWM-LES with computationally economic costs.

Cardiovascular risk associated with fetal growth restriction (FGR) could result from an early impaired vascular function. However, whether this effect results in premature vascular aging has not been addressed. We studied the ex vivo reactivity of carotid and femoral arteries in fetal (near term), adults (eight months-old) and aged (16 months-old) guinea pigs in normal (control) and FGR offspring. Additionally, an epigenetic marker of vascular aging (i.e., LINE-1 DNA methylation) was evaluated in human umbilical artery endothelial cells (HUAEC) from control and FGR subjects. Control guinea pig arteries showed an increased contractile response (KCl-induced) and a progressive impairment of NO-mediated relaxing responses as animals get older. FGR was associated with an initial preserved carotid artery reactivity as well as a later significant impairment in NO-mediated responses. Femoral arteries from FGR fetuses showed an increased contractility but a decreased relaxing response compared with control fetuses, and both responses were impaired in FGR-adults. Finally, FGR-HUAEC showed decreased LINE-1 DNA methylation compared with control-HUAEC. These data suggest that the aging of vascular function occurs by changes in NO-mediated responses, with limited alterations in contractile capacity. Further, these effects are accelerated and imposed at early stages of development in subjects exposed to a suboptimal intrauterine environment.

Persistent infection is a characteristic feature of babesiosis, a worldwide, emerging tick-borne disease caused by members of the genus Babesia. Persistence of Babesia infection in reservoir hosts increases the probability of survival and transmission of these pathogens. Laboratory tools to detect Babesia in red blood cells include microscopic detection using peripheral blood smears, nucleic acid detection (polymerase chain reaction and transcription mediated amplification), antigen detection, and antibody detection. Babesia microti, the major cause of human babesiosis, can asymptomatically infect immunocompetent individuals for up to two years. Chronically infected blood donors may transmit the pathogen to another person through blood transfusion. Transfusion-transmitted babesiosis causes severe complications and death in about a fifth of cases. Immunocompromised patients, including those with asplenia, HIV/AIDS, malignancy, or on immunosuppressive drugs, often experience severe disease that may relapse up to two years later despite anti-Babesia therapy. Persistent Babesia infection is promoted by Babesia immune evasive strategies and impaired host immune mechanisms. The health burden of persistent and recrudescent babesiosis can be minimized by development of novel therapeutic measures, such as new anti-parasitic drugs or drug combinations, improved anti-parasitic drug duration strategies, or immunoglobulin preparations; and novel preventive approaches, including early detection methods, tick-avoidance, and blood donor screening.

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D2/D3 receptor (D2/D3R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D2/D3R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D2/D3R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D2/D3R.

The early 2020s witnessed an unprecedented overlap of multiple global crises. This longitudinal study examined the compounded effects of multiple intersecting global crises on mental health outcomes in a representative cohort of East German adults. We investigated how perceived threats (PT) from climate change (PT-CLC), COVID-19 (PT-COV), the Russia-Ukraine War (PT-RUW), and rising costs of living (PT-RCL) will impact various aspects of mental health from 2021 to 2022. This research question addresses whether these crises exacerbate mental health issues and how their effects differ across various mental health outcomes. Methods: We conducted a longitudinal study with 319 participants (mean age 49.9 years, 54.5% female) from the Saxony Longitudinal Study. Data were collected in two waves: March-July 2021 and September-December 2022. We used linear mixed-effects models to analyze both unadjusted group trends and adjusted individual-level effects on physical complaints, mental distress, sleep problems, life satisfaction, and self-rated health. Results: Unadjusted analyses revealed significant increases in mental distress and sleep problems over time, whereas physical complaints, life satisfaction, and self-rated health remained stable at the group level. Adjusted analyses showed that higher PT-RCL and PT-COV were significantly associated with increased physical complaints, mental distress, sleep problems, and decreased life satisfaction, even when group-level changes were not significant. Conclusions: This study highlights the complex impact of intersecting global crises on mental health, emphasizing the importance of considering both population-level trends and individual perceptions. The findings suggest that economic and pandemic-related stressors have more immediate effects on mental health outcomes compared to more distant threats, such as climate change or geopolitical conflicts.

Indolizidines have long been recognized for their valuable bioactivities, their common feature being a bicyclic structure connected via a nitrogen atom. Traditionally, plants have been identified as the primary producers. However, recent discoveries have revealed that certain bacterial strains belonging to the genus of actinomycetes also possess the ability to synthesize various indolizidine-based compounds. Among these strains, Streptomyces sp. HNA39, Saccharopolyspora sp. RL78, and Streptomyces NCIB 11649 have been identified as producers of cyclizidines, characterized by their distinctive cyclopropyl moiety. Additionally, Streptomyces griseus OS-3601 synthesizes a unique class of indolizidine derivatives known as iminimycins, distinguished by their rare imine-cation structure. Protoplast fusion of a Streptomyces griseus strain with Streptomyces tenjimariensis resulted in a new indolizidine named indolizomycin. This review aims to provide an overview of known bacterial indolizidine producers, summarize current knowledge regarding the biosynthesis of cyclizidines and iminimycins, and assess their respective bioactivities.

With the rising trend of consumers being offered by start-up companies portable devices and applications for checking quality of purchased products, it appears of paramount importance to assess the reliability of miniaturized sensors embedded in such devices. Here, eight sensors were assessed for food fraud applications in skimmed milk powder. The performance was evaluated with dry- and wet-blended powders mimicking adulterated materials by addition of either ammonium sulfate, semicarbazide, or cornstarch in the range 0.5-10% of profit. The quality of the spectra was assessed for an adequate identification of the outliers prior to a deep assessment of performance for both non-targeted (soft independent modelling of class analogy, SIMCA) and targeted analyses (partial least square regression with orthogonal signal correction, OPLS). Here, we show that the sensors have generally difficulties in detecting adulterants at ca. 5% supplementation, and often fail in achieving adequate specificity and detection capability. This is a concern as they may mislead future users, particularly consumers, if they are intended to be developed for handheld devices available publicly in smartphone-based applications.