Background: In most cases, intra-labyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors is various but affects mostly the cochlea. Extirpation of the ILS, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intra-labyrinthine schwannoma. Methods: In three patients, the TRD was used for the tumor removal of ILS. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach, and an additional second-turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-minute procedure. MRI control confirmed a complete removal on the postoperative day in both cases. Conclusion: In vivo handling of the device confirmed a straightforward handling for tumor removal. MRI scanning showed a complete removal of the tumor by the TRD.

Transglutaminase 2 (TG2) is a critical cancer cell survival factor that activates several signaling pathways to foster drug resistance, cancer stem cell survival, metastasis, inflammation, epithelial mesenchymal transition, and angiogenesis. All-trans retinoic acid (ATRA) and chemotherapy have been the standard treatments for acute promyelocytic leukemia (APL), but clinical studies have shown that arsenic trioxide (ATO), alone or in combination with ATRA, can improve outcomes. ATO exerts cytotoxic effects in a variety of ways by inducing oxidative stress, genotoxicity, altered signal transduction, and/or epigenetic modification. In the present study, we showed that ATO increased ROS production and apoptosis ratios in ATRA-differentiated NB4 leukemia cells and that these responses were enhanced when TG2 was deleted. The combined ATRA+ATO treatment also increased the amount of nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor, an adaptive regulator of cellular oxidative stress response, and proteolytic activity of calpain, resulting in TG2 degradation and reduced survival of WT leukemia cells. We further showed that upon ATO treatment, the induced TG2 protein expression was degraded in the MCF-7 epithelial cell line, and primary peripheral blood mononuclear cells, thereby sensitizing these cell types to apoptotic signals.

Epistemological naturalism dismisses the notion that epistemology is a basis for the empirical sciences. In particular, it rejects the demand for a general justification of induction. Making inductive generalisations is a basic habit among humans. There is no such thing as a logic of inductive inference. The role of induction in science is heuristic; it is our way of inventing new theoretical predicates and developing theories. We discover new laws by applying inductive thinking; but this is not any kind of inference which can be evaluated as more or less rational.

We calculate the sound velocity and the damping rate of the collective excitations of a 2D fermionic superfluid in a non-perturbative manner. Specifically, we focus on the Anderson-Bogoliubov excitations in the BEC-BCS crossover regime, as these modes have a soundlike dispersion at low momenta. The calculation is performed within the path integral formalism and the Gaussian pair fluctuation approximation. From the action functional, we obtain the propagator of the collective excitations and determine their dispersion relation by locating the poles of this propagator. We find that there is only one kind of collective excitation, which is stable at $T=0$ and has a sound velocity of $v_{F}/\sqrt{2}$ for all binding energies, i.e. throughout the BEC-BCS crossover. As the temperature is raised, the sound velocity decreases and the damping rate shows a non-monotonous behavior: after an initial increase, close to the critical temperature $T_{C}$ the damping rate decreases again. In general, higher binding energies provide higher damping rates. Finally, we calculate the response functions and propose that they can be used as another way to determine the sound velocity.

We revise the definition of graph operations in [WDK2018] and adapt correspondingly the construction of graph term algebras. As a first contribution to a prospective research field Universal Graph Algebra, we generalize some basic concepts and results from algebras to graph algebras. To tackle this generalization task, we revise and reformulate traditional set-theoretic definitions, constructions and proofs in Universal Algebra by means of more category-theoretic concepts and constructions. Especially, we generalize the concept generated subalgebra and prove that all monomorphic homomorphisms between graph algebras are regular. Derived graph operations are the other main topic. After an in depth analysis of terms as representations of derived operations in traditional algebras, we identify three basic mechanisms to construct new graph operations out of given ones: parallel composition, instantiation, and sequential composition. As a counterpart of terms, we introduce graph operation expressions with a structure as close as possible to the structure of terms. We show that the three mechanisms allow us to construct for any graph operation expression a corresponding derived graph operation in any graph algebra.

The normal ageing process significantly affects resistance arteries, leading to various biological and physiological consequences. Systolic hypertension is a common occurrence in ageing individuals, accompanied by increased large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, there is a progressive elevation in mean arterial pressure, supported by clinical and epidemiological evidence as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. Dysregulation of calcium entry channels (T-type, L-type, TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to age-related dysregulation of myogenic tone. Flow-mediated vasodilatation, a hallmark of endothelial function, is compromised in ageing. This result of endothelial dysfunction is related to oxidative stress, lower nitric oxide bioavailability and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall, often seen in conjunction with outward remodeling (in normotension), but can also present as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of extracellular matrix fiber proteins and actin cytoskeletal components. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation, often referred to as "inflammaging”, play substantial roles in age-related vascular dysfunction. Due to its role in regulation of vascular tone as well as structural proteins, the RhoA/Rho-kinase pathway becomes a new target in age-related vascular dysfunction and associated diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance overall vascular health.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

It is the aim of this article to introduce a concise notation that is be able to capture the most important dimensions of sexuality and thus facilitate discussions. Moreover, the major three dimensions - sex, gender, and sexual orientation - lead to a straightforward classification which motivates the quest for stringent explanatory models, some of which are also discussed.

Control of nutrients, mainly nitrogen (N) and phosphorus (P), plays a significant role in preventing cyanobacterial blooms (harmful algal blooms (HABs)). This study aimed at evaluating changes in the risk of the occurrence of cyanobacterial blooms and advancing the understanding of how N and P affect the growth of cyanobacteria in a eutrophic lake, Lake Vombsjön, in southern Sweden. Statistical analysis was used to demonstrate the pattern of cyanobacterial blooms, that the highest content present in September and the later that algal blooms occur, the more likely it is a cyanobacterial bloom as cyanobacteria became dominating in October and November (90%). Two hypothesises tested in Lake Vombsjön confirmed namely that a high total phosphorus (TP) level correlates with an abundance of cyanobacteria and that low N:P ratio (total nitrogen/total phosphorus < 20) favours the growth of cyanobacteria. To control the growth of cyanobacteria in Lake Vombsjön, the TP level should be kept below 20 µg/L and the N:P ratio be maintained at a level of over 20. The two species Planktothrix agardhii, and Pseudanabaena spp. should be carefully monitored especially in late autumn. Future work should consider any high degree of leakage from the sediment of the dissolved phosphorus available there.

Exploring the dynamic behavior of cellular metabolism requires a standard laboratory method that guarantees rapid sampling and extraction of the cellular content. We propose a versatile sampling technique applicable to cells with different cell wall and cell membrane properties. The technique is based on irreversible electroporation with simultaneous quenching and extraction by using a microfluidic device. By application of electric pulses in the millisecond range, permanent lethal pores are formed in the cell membrane of Escherichia coli and Saccharomyces cerevisiae, facilitating the release of the cellular contents; here demonstrated by the measurement of glucose-6-phosphate and the activity of the enzyme glucose-6-phosphate dehydrogenase. The successful application of this device was demonstrated by pulsed electric field treatment in a flow-through configuration of the microfluidic chip in combination with sampling, inactivation, and extraction of the intracellular content in a few seconds. Minimum electric field strengths of 10 kV/cm for E. coli and 7.5 kV/cm for yeast S. cerevisiae were required for successful cell lysis. The results are discussed in the context of applications in industrial biotechnology, where metabolomics analyses are important.

The multi-material design and the adaptability of a modern process chain require joining connections with specifically adjustable mechanical, thermal, chemical or electrical properties, whereby previous considerations have focused primarily on the mechanical properties. With clinching, the multitude of possible combinations of requirements, materials and component or joint geometry makes it impossible to determine these joint properties empirically. As a result of the established and empirically based procedure, no model exists to date that considers all questions of joinability, i.e. the materials (suitability for joining), the design (joining safety) and the production (joining possibility) and allows a calculation of the achievable properties. It is therefore necessary to describe the physical properties of the joint as a function of the three bonding mechanisms force closure, form closure and material closure in relation to the application. This approach enables the illustration of the relationships along the causal chain "joint requirement - binding mechanism - joining parameters". In this way the adaptability of the mechanical joining technology can be improved. A geometric comparison is made using metallographic cross sections, of clinched joints of the combination of aluminum and steel. The torsional testing of the rotationally symmetric clinching points for detection of the mechanical stress state are qualified as examination method and technological test. By measuring the electrical resistance in the base material, in the clinch joint and during the production cycle (after clinching, before precipitation hardening and after precipitation hardening), this change in the stress state can also be detected.

Auckland Island pigs represent an inbred population of feral pigs isolated on the subantarctic island for over 100 years. The animals have been maintained under pathogen-free conditions in New Zealand, they are well characterized virologically and have been used as donor sources in first clinical trials of porcine neonatal islet cell transplantation for the treatment of human diabetes patients. The animals do not carry any of the xenotransplantation-relevant viruses and in the first clinical trials no porcine viruses including porcine endogenous retroviruses (PERVs) have been transmitted to the human recipients. PERVs pose a special risk in xenotransplantation since they are part of the pig genome. When the copy number of PERVs in these animals was analyzed using droplet digital PCR and primers binding to a conserved region of the polymerase gene (PERVpol), a copy number typical for Western pigs was found, confirming previous phylogenetic analyses of microsatellites and mitochondrial analyses showing a closer relationship to European pigs than to Chinese pigs. When kidney cells from very young piglets were analyzed, only around 20 PERVpol copies were detected. Using these cells as donors in somatic cell nuclear transfer (SCNT), animals were born showing a PERVpol copy numbers between 35 and 56. This data indicates that Auckland Is-land pigs have a similar copy number in comparison with other Western pig breeds and that the copy number is higher in adult animals compared with cells from young piglets. Most im-portantly, PERV-C free animals were selected and the absence of additional eight porcine viruses was demonstrated.

Auckland Island pigs represent an inbred population of feral pigs isolated on the subantarctic island for over 100 years. The animals have been maintained under pathogen-free conditions in New Zealand, they are well characterized virologically and have been used as donor sources in first clinical trials of porcine neonatal islet cell transplantation for the treatment of human dia-betes patients. The animals do not carry any of the xenotransplantation-relevant viruses and in the first clinical trials no porcine viruses including porcine endogenous retroviruses (PERVs) have been transmitted to the human recipients. PERVs pose a special risk in xenotransplantation since they are part of the pig genome. When the copy number of PERVs in these animals was analyzed using droplet digital PCR, a copy number typical for Western pigs was found, confirming previous phylogenetic analyses of microsatellites and mitochondrial analyses showing a closer relationship to European pigs than to Chinese pigs. When kidney cells from very young piglets were analyzed, only around 20 PERVpol copies were detected. Using these cells as nuclear donors in a somatic cell nuclear transfer (SCNT), animals were born showing PERVpol copy numbers between 35 and 56. This data indicates that Auckland Island pigs have a lower copy number in comparison with other Western pig breeds and that the copy number is higher in adult animals compared with cells from young piglets. Most importantly, PERV-C free animals were selected and the absence of additional eight porcine viruses was demonstrated.

The COVID-19 pandemic is shifting teaching to an online setting all over the world. The Galaxy framework facilitates the online learning process and makes it accessible by providing a library of high-quality community-curated training materials, enabling easy access to data and tools, and facilitates sharing achievements and progress between students and instructors. By combining Galaxy with robust communication channels, effective instruction can be designed inclusively, regardless of the students' environments.

The Digital Twin is one of the big technology trends of the last decade. In the course of its rapid expansion into the various fields of application, many different definitions emerged, tailored to the respective applications. Taxonomies can cluster the diversity and define application-specific archetypes. This paper presents a characterization of the Digital Twin in the context of structural mechanics and lightweight design. It begins by exploring various definitions of the Digital Twin concept and its application in different industries. The paper further analyzes the product life cycle of structures, dividing it into the design and operational phases and identifying the requirements for a Digital Twin in each phase. The structural design process is examined, including the definition of a structure and the stages of the product development process. Additionally, the paper discusses the operational phase of structures, highlighting the need for continuous monitoring, evaluation, and adaptation through Structural Health Monitoring (SHM) systems. The paper proposes two archetypes of Digital Twins for structures: a structure-designing Digital Twin for the design phase and a structure-monitoring Digital Twin for the operational phase. The findings provide a framework for implementing Digital Twins in structural mechanics, enabling digital design and monitoring of structures for improved performance and maintenance strategies.

This paper present a platform for airborne sensor applications using low-cost, open-source components carried by an easy-to-fly unmanned aircraft vehicle (UAV). The system, available in open-source [1], is designed for researchers, students and makers for a broad range of their exploration and data-collection needs. The main contribution is the extensible architecture for modularized airborne sensor deployment and real-time data visualisation. Our open-source Android application provides data collection, flight path definition and map tools. Total cost of the system is below 800 dollars. The flexibility of the system are illustrated by mapping the location of Bluetooth beacons (iBeacons) on a ground field and by measuring water temperatures in a lake.

Pre-mRNA splicing is an essential process orchestrated by the spliceosome, a dynamic complex assembled stepwise on pre-mRNA. We have previously identified that USH1G protein SANS regulates pre-mRNA splicing by mediating the intra-nuclear transfer of the spliceosomal U4/U6.U5 tri-snRNP complex. During this process, SANS interacts with the U4/U6 and U5 snRNP-specific proteins PRPF31 and PRPF6 and regulates splicing, which is disturbed by variants of USH1G/SANS causative for human Usher syndrome (USH) the most common form of hereditary deaf-blindness.Here, we aimed to gain further insight into the molecular interaction of the splicing molecules PRPF31 and PRPF6 to the CENTn domain of SANS using fluorescence resonance energy transfer assays in cells and in silico deep learning-based protein structure predictions. This demonstrates that SANS directly binds via two distinct conserved regions of its CENTn to the two PRPFs. In addition, we provide evidence that these interactions occur sequentially and a conformational change of an intrinsically disordered region to a short α-helix of SANS CENTn2 is triggered by binding of PRPF6. Furthermore, we found that pathogenic variants of USH1G/SANS perturb the binding of SANS to both PRPFs implying a significance for the USH1G pathophysiology.

Critically the paper argues that a truly people-centered technology supported chronic care system can only be designed by understanding and responding to the needs, attributes and capabilities of the most vulnerable in society. The paper suggests innovative ways of supporting interactions with these ‘end-users’ and highlights how reflection on these approaches can contribute to emancipating both the health system to move towards more socially inclusive e-health solutions.

Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant health care burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PK) and pharmacodynamics (PD). Ocular quantitative systems pharmacology (QSP) models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based pharmacokinetic (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models employing molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eye and describe cellular systems, data repositories as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for post-operative fibrosis after glaucoma surgery.

Purpose: This study evaluates the performance of the Early Intervention Physiotherapist Framework (EIPF) for injured workers. This study provides a proper follow-up period (3 years) to examine the impacts of the EIPF program on injury outcomes such as return to work (RTW) and time to RTW. This study also identifies the factors influencing the outcomes. Methods: The study was conducted on data collected from compensation claims of people who were injured at work in Victoria, Australia. Injured workers who commenced their compensation claims after the first of January 2010 and had their initial physiotherapy consultation after the first of August 2014 are included. To conduct the comparison, we divided the injured workers into two groups: physiotherapy services provided by EIPF-trained physiotherapists (EP) and regular physiotherapists (RP) over the three-year intervention period. We used three different statistical analysis methods to evaluate the performance of the EIPF program. We used descriptive statistics to compare two groups based on physiotherapy services and injury outcomes. We also completed survival analysis using Kaplan-Meier curves in terms of time to RTW. We developed univariate and multivariate regression models to investigate whether the difference in outcomes achieved after adjusting for significantly associated variables. Results: The results showed that physiotherapists in the EP group on average dealt with more claims (over twice as many) than those in the RP group. Time to RTW for the injured workers treated by the EP group was significantly lower than for those who were treated by the RP group, indicated by descriptive, survival and regression analyses. Earlier intervention by physiotherapists led to earlier RTW. Conclusion: This evaluation showed that the EIPF program achieved successful injury outcomes three years after implementation. Motivating physiotherapists to intervene earlier in the recovery process of injured workers by initial consultation helps to improve injury outcomes.

The mantle mass flow interconnected with the process of Glacial Isostatic Adjustment (GIA) and the reformation of the Earth’s crust constantly perturbs the observed gravity field towards a hypothetic isostatic state. We analyse the temporal changes of the gravity field from the GRACE data, using different mathematical and/or statistical methods to detect the GIA amidst other gravity signals. A number of gravimetric post-glacial land uplift rate (LUR) modelling methods are investigated and compared with the data from a total number of 515 GPS stations and preferred GIA forward models in Fennoscandia and North America. We investigate three mathematical methods, namely regression, principal component, and independent component analysis (ICA) to extracting the GIA signal from the GRACE monthly geoid heights. We use some regularization techniques to exploit the GRACE monthly data to their maximum spatial resolution and to increase the Signal to Noise Ratio of their short wavelengths. Near the centres of the study areas the gravimetric LUR model using the fast-ICA algorithm of Hyvärinen and Oja (2000) is shown to be in a complete agreement with the GPS data and the predictions of the GIA forward models, and for the whole areas, subject to epeirogeny movement of the two regions, their discrepancies reach to the extrema at -1.8 and +3.3, and -4.5 and +7.5 mm/a, respectively. We show that the largest discrepancies between the gravimetric model using the ICA method and the GIA forward model, occur for the sub-regions likely collocated with strong ice mass change signals.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

In this study, we investigate the magnetization behavior of coaxial nanowires fabricated through the sol-gel electrospinning method. Our analysis uncovers a significant reduction in coercivity for CoFe2O4 nanowires when BaTiO3 is used as the shell material, effectively transforming them from hard to soft magnetic. This intriguing behavior is attributed to the magnetization reversal effect at the interface between ferromagnetic and paramagnetic regions, and it is also observed in NiFe2O4 and Fe2O3 nanowires. Surprisingly, introducing a GdBa2Cu3O7 shell induces a similar effect. Additionally, we employ magnetic impedance measurements on the coaxial nanowires, unveiling their potential for magnetic field sensing applications.

During disaster response, clouds or darkness can prevent the use of optical images for detecting consequences of natural disasters, including landslides. In these situations, radar images can be used to detect changes more rapidly. However, Synthetic Aperture Radar (SAR) backscatter intensity images are underutilized for landslide detection. Unfortunately, there remains a lack of understanding about how to interpret landslide signatures in SAR imagery. In this study, we investigate how the morphometric features and material properties of landslides, and preexisting land cover, control their expression in SAR backscatter intensity change images. Trends in the spatial and temporal signatures of over 1000 landslides in 30 diverse case studies are investigated, using multi-temporal composites and dense time-series of Sentinel-1 C-band SAR backscatter intensity data. The results show that the orientation of landslide surfaces relative to the sensor, pre-existing land cover, and the roughness of the landslide surface, determine whether landslides will produce an increase or decrease in backscatter intensity values. In certain cases, we can identify morphometric features of landslides (e.g. scarps, transit zone, deposits, ponding) and material properties. Generally, we see that landslides appear most clearly with a strong increase in intensity when they occur in herbaceous vegetation or non-vegetated ground surfaces, due to an increase in surface roughness. While in forested or densely vegetated areas, landslides produce a more complex signature with both decreases due to radar shadow and vegetation removal, and an adjacent edge of increased intensity due to double bounce and direct return from vertical tree trunks and convex edges. In most cases, rough deposits produce an increase in intensity, while smooth deposits (e.g. from mudslides) exhibit specular reflection, and thus show decreased values. Landslides are less visible in cases with pre-event very rough ground, or mixed vegetation conditions. The conceptual model developed can aid interpretation of landslides in SAR imagery, and provide domain knowledge needed to train models for automatic landslide detection.

Residual stresses in fiber metal laminates (FML) inevitably develop during the manufacturing process. The main contributor to these stresses is the difference in the coefficients of thermal expansion (CTE) between fibers and metal in combination with high process temperatures. To quantify these stresses, the use of specimens with an asymmetric layup is an easily adaptable method. The curvature that develops after the manufacturing of flat laminates with an asymmetrical layer stack is a measure of the level of residual stresses evolving during cure. However, the accuracy of the curvature evaluation is highly dependent on specimen design and other influencing parameters. In this work a large set of FML specimens is investigated to identify relevant influencing parameters and derive conclusions about specimen design and evaluation techniques. For certain layups and process parameters, there is a good correlation between the curvature and the stress-free temperature, which is further covered by analytical solutions for bimetals. This correlation is the basis to transfer curvature into a stress-free temperature that can consequently be used for the quantification of residual stress levels in more complex FMLs. The transfer is validated by in-situ strain measurements during cure using a strain gage technique. Based on the results, the application of asymmetric specimens for residual stress characterization in more complex laminates is presented in the form of a workflow.

This study introduces a novel computational approach for testing conditional independence (BB CI test) within causal Directed Acyclic Graphs (DAGs), leveraging Bayesian non-parametric bootstrap and machine learning techniques. Our method offers an alternative for validating the assumptions underpinning causal DAGs. Through simulation studies and an industrial case analysis, we demonstrate the test procedure in accurately assessing conditional independence, comparing it with the Generalized Covariance Measure (GCM) test. Our findings suggest that the BB CI test is advantageous in scenarios where existing methods may falter due to violations of model assumptions. This research contributes to the causal inference literature by providing a computational tool for researchers and practitioners to validate causal models.

The atomic structures of Zn and Na borophosphate glasses were studied by X-ray and neutron diffraction. Peaks assigned to the B−O, P−O, and O−O distances confirm that only BO4 units co-exist with the PO4 tetrahedra. The Zn−O and Na−O coordination numbers are found to be a little larger than four. The narrowest peaks of the Zn−O first-neighbor distances exist for the glasses along a line connecting the Zn(PO3)2 and BPO4 compositions (50 mol% P2O5) which is explained by networks of ZnO4, BO4, and PO4 tetrahedra with twofold coordinated oxygens. Calculated amounts of the available oxygen support this interpretation. Broadened peaks occur for glasses with lower P2O5 contents, consistent with the presence of threefold coordinated oxygens. The two distinct P−O peak components of the Zn and Na borophosphate glasses differ in their relative abundances which is interpreted by Na+ cations that coordinate oxygens in some P−O−B bridges, something not seen for the Zn2+ ions.

On the basis of a stocktaking on PVC in Europe and on a current ECHA investigation report, we conclude that regulatory action at EU level is recommended. We support ECHA's regulatory proposals in the main, but come to a more comprehensive proposal for the phasing-out of PVC beyond the area of electrical installations. PVC stored in buildings and infrastructure to date amounts to around 160 million tonnes ("stock") and this mass is still increasing. Parts from the stock have entered the waste management sector for years and their mass is gradually increasing. Neither material, chemical nor energy recovery will be able to absorb these incoming quantities. We therefore come to the conclusion that PVC should be collected separately and disposed of in an infrastructure designed for chlorine recovery. The required infrastructure should be set up and operated by the chemical industry. So, PVC will lose its status as a particularly economically favorable plastic. In view of the constantly increasing stock, we recommend phasing-out the production of virgin PVC as early as possible. In our opinion, this would also be justifiable because the effects of the closed loop recycling announced by VinylPlus ('Vinyl') would go in the same direction.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

Modulation of nociception allows animals to prioritise their survival by adapting their behaviour in different contexts. In mammals, this is executed by neurons from the brain, and is referred to as the descending control of nociception. Whether insects have this control, or have the neural circuits underpinning it, has not been clarified. Here, we review evidence supporting descending control of nociception control in insects, and consider which neuronal sub-types and brain areas may be involved.

Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is the tryptase. To look deeper into the question their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting such regulatory functions may involve controlling excessive TH2 mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15 and IL-21 indicating a potent negative feedback loop on TH2 immunity.

Background and Objectives: Jehovah's Witnesses (JW) reject the transfusion of blood components based on their religious beliefs even if they are in danger of harm or death. In cardiac surgery, this significantly reduces the margin of safety and leads to ethical conflicts. Informed consent should be carefully documented and the patient's family should be involved. This study aims to compare the postoperative course of JW who underwent major cardiac surgery with a similar population of non-Witnesses (NW). Patients and Methods: Demographic, procedural, and postoperative data of all consecutive JW who underwent cardiac surgery at our institution were obtained from the records. They were compared with a propensity score matched group of NW. Anemic JW were treated with erythropoietin and/or iron as needed. Cardiac surgery was performed by experienced surgeons using median sternotomy and cardiopulmonary bypass. Common blood-sparing techniques were routinely used. Periprocedural morbidity and mortality were statistically evaluated for both groups. Results: 32 JW and 64 NW were part of the matched dataset showing no demographic or procedural differences. EPO was used preoperatively in 34.4% and postoperatively in 15.6% of JW but not in NW. Preoperative hemoglobin levels were similar (JW, 8.09±0.99 mmol/l; NW, 8.18±1.06; p=0.683). JW did not receive any transfusions except for one who revoked, while NW transfusion rates were 2.5±3.1 units for red cells (p&lt;0.001) and 0.3±0.8 for platelets (p=0.018). Postoperative levels differed significantly for hemoglobin (JW, 6.05±1.00 mmol/l; NW, 6.88±0.87; p&lt;0.001), and hematocrit (JW, 0.29±0.04; NW, 0.33±0.04; p&lt;0.001) but not for creatinine. Early mortality was similar (JW, 6.3%; NW, 4.7%; p=0.745). There were more pacemakers and pneumonias in JW, while all other postoperative conditions were not different. Conclusions: Real-world data indicate that Jehovah's Witnesses can safely undergo cardiac surgery provided that patients are preconditioned and treated by experienced surgeons who use blood-saving strategies. Postoperative anemia is observed but does not translate into a worse clinical outcome. This is consistent with other studies.

Sterilisation and preservation of vesicle formulations are an important consideration for their viable manufacture for industry applications, particular those intended for medicinal use. Here we undertake an initial investigation of the stability of hybrid lipid – block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd12-PEO11 and PBd22-PEO14) mixed with the phospholipid POPC considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.

More than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called "Generelle Morphologie der Organismen" (General Morphology of Organisms) in the first volume of which he formulated his Biogenetic law, famously stating that ontogeny recapitulates phylogeny (Rieppel 2019). Here we describe Haeckel´s original idea as first formulated in the “Generelle Morphologie der Organismen” and later further developed in other publications until the present situation in which molecular data are used to test the "hour-glass model", which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while travelling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory. We also follow the further development and reformulations of the Gastraea theory by other scientists, notably the Russian school (Levit, 2007). Ilya Metchnikov developed the Phagocytella hypothesis for the origin of metazoans based on studies of a colonial flagellate. Alexey Zakhvatin focused on deducing the ancestral life cycle and the cell types of the last common ancestor of all metazoans, and Mikhailov recently pursued this line of research further.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Thermal and catalytic pyrolysis of virgin low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP) and mixtures of LDPE/PP were carried out in a 200 ml laboratory scale batch reactor at 460 °C in a nitrogen atmosphere. Thermogravimetric analysis (TGA) was carried out to study the thermal and catalytic degradation of the polymers at a heating rate of 10 °C/min. The amount of PP was varied in the LDPE/PP mixture to explore its effect on the reaction. In thermal degradation (TGA) of LDPE/PP blends, a lower decomposition temperature was observed for LDPE/PP mixtures compared to pure LDPE, indicating interaction between the two polymer types. In the presence of a catalyst (CAT-2), the degradation temperatures for the pure polymers were reduced. The TGA results were validated in a batch reactor using PP and LDPE respectively. Thermal cracking results showed that the oil product contains a significant amount of gasoline (C7 − C12) and diesel (C13 − C20) hydrocarbon fractions. The catalyst enhanced cracking at lower temperatures and narrowed the hydrocarbon distribution in the oil towards the gasoline range fraction (C7 – C12). The result suggests that the oil produced from catalytic pyrolysis of waste plastics has a potential as an alternative fuel.

In aqueous solution planar bis(1,2-dithiooxalato)nickelates(II), [Ni(dto)2]2- react with lanthanide ions (Ln3+) to form pentanuclear, hetero-bimetallic complexes of the general composition [{Ln(H2O)n}2{Ni(dto)2}3] · x H2O (n = 4 or 5; x = 9 - 12). Two complexes of this series, [{Pr(H2O)5}2{Ni(dto)2}3] · 11 H2O, Pr2Ni3 1 and [{Gd(H2O)5}2{Ni(dto)2}3] · 11 H2O, Gd2Ni3 2 were synthesized and characterized by single crystal X-ray structure analysis, X-ray powder diffraction, and IR spectroscopy. All Ln2Ni3 complexes crystallize as monoclinic crystals in the space group P21/c.

The glycoprotein hormones luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and chorionic gonadotropin consist of a common alpha-subunit and a hormone-specific beta-subunit. The alpha-subunit is expressed in thyrotrophs, gonadotrophs, and placental cells, and its expression is regulated by extracellular signal molecules. Here, we assessed the regulation of the gene encoding the alpha-subunit in placental JEG-3 cells, using a chromatin-embedded reporter gene under the control of the glycoprotein hormone alpha-subunit promoter. The results show that stimulation of the cells with forskolin, an activator of adenylate cyclase, induced transcription of a reporter gene controlled by the alpha-subunit promoter. Similarly, expression of a nuclear-targeted catalytic subunit of cAMP-dependent protein kinase increased reporter gene transcription. Expression experiments involving constitutively active mutants of MKK6 and MEKK-1 showed that the alpha-subunit promoter is responsive to activation of p38 protein kinase but only slightly responsive to activation of c-Jun N-terminal protein kinase. Finally, we show that stimulation of a Galphaq-coupled designer receptor triggers transcription of a reporter gene controlled by the glycoprotein hormone alpha-subunit promoter, mediated by the transcription factor CREB. Deletion mutagenesis highlights the importance of a tandem cAMP response element within the alpha-subunit promoter that acts as a point of convergence for different signaling pathways.

We have developed additive logistic models for the occurrence of lightning, large (≥ 2 cm), and very large (≥ 5 cm) hail to investigate the evolution of these hazards in the past, in the future, and for forecasting applications. The models, trained with lightning observations, hail reports, and predictors from atmospheric reanalysis, assign an hourly probability to any location and time on a 0.25° × 0.25° × 1-hourly grid as a function of reanalysis-derived predictor parameters, selected following an ingredients- based approach. The resulting hail models outperform the Significant Hail Parameter and the simulated climatological spatial distributions and annual cycles of lightning and hail are consistent with observations from storm report databases, radar, and lightning detection data. As a corollary result, CAPE released above the -10°C isotherm was found to be a more universally skilful predictor for large hail than CAPE. In the period 1950–2021, the models applied to the ERA5 reanalysis indicate significant increases of lightning and hail across most of Europe, primarily due to rising low-level moisture. The strongest modelled hail increases occur in northern Italy with increasing rapidity after 2010. Here, very large hail has become 3 times more likely than it was in the 1950s. Across North America trends are comparatively small, apart from isolated significant increases in the direct lee of the Rocky Mountains and across the Canadian Plains. In the southern Plains, a period of enhanced storm activity occurred in the 1980s and 1990s.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Optical Character Recognition (OCR) on historical printings is a challenging task mainly due to the complexity of the layout and the highly variant typography. Nevertheless, in the last few years great progress has been made in the area of historical OCR, resulting in several powerful open-source tools for preprocessing, layout recognition and segmentation, character recognition and post-processing. The drawback of these tools often is their limited applicability by non-technical users like humanist scholars and in particular the combined use of several tools in a workflow. In this paper we present an open-source OCR software called OCR4all, which combines state-of-the-art OCR components and continuous model training into a comprehensive workflow. A comfortable GUI allows error corrections not only in the final output, but already in early stages to minimize error propagations. Further on, extensive configuration capabilities are provided to set the degree of automation of the workflow and to make adaptations to the carefully selected default parameters for specific printings, if necessary. Experiments showed that users with minimal or no experience were able to capture the text of even the earliest printed books with manageable effort and great quality, achieving excellent character error rates (CERs) below 0.5%. The fully automated application on 19th century novels showed that OCR4all can considerably outperform the commercial state-of-the-art tool ABBYY Finereader on moderate layouts if suitably pretrained mixed OCR models are available. The architecture of OCR4all allows the easy integration (or substitution) of newly developed tools for its main components by standardized interfaces like PageXML, thus aiming at continual higher automation for historical printings.

The aims of the review were to elucidate the spatial variation in sea ice algae primary production rates and biomasses (Chl a) in the Canadian Arctic – Greenland region, characterized by comparable physical settings. A database was compiled from 30 studies of sea ice algae primary production rates, biomasses (Chl a), snow and ice thicknesses, ice types, nutrient (Si(OH)4, PO4, (NO3+NO2), and (NH4) concentrations in ice and below ice from the region. Production rates were significantly high (463 mg C m-2 d-1) in Resolute Bay and in Northern Baffin Bay (317 mg C m-2 d-1) both in Canadian Arctic, as compared to a rate of 0.2 mg C m-2 d-1 in northeast Greenland. The biomasses reached 340 mg Chl a m-2 in Resolute Bay in comparison to a 0.02 mg Chl a m-2 in southwest Greenland. Primary production at other Canadian and Greenland sites were comparable but sea ice Chl a was higher (15.0 ± 13.4 mg Chl a m-2) at Canadian sites as compared to Greenland (0.8 ± 0.5 mg Chl a m-2). Resolute and Northern Baffin Bays production rates were significantly higher when compared to other Arctic Ocean sites outside the studied region. The review concludes that high production rates and biomasses in Resolute and Northern Baffin Bay’s were related to inflow and mixing of nutrient rich waters of Pacific origin. A conceptual model with drivers and inhibitors of sea ice algae primary production is projected, and the database compiles a dataset of published data for further studies.

Cardiac damage has been attributed to SARS-Cov-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population.

Cows produce saliva in very large quantities to lubricate and facilitate food processing. Estimates indicate an amount of 50-150 liter per day. Human saliva has previously been found to contain numerous antibacterial components, such as lysozyme, histatins, members of the S-100 family and lactoferrin to limit pathogen colonization. Cows are dependent of a complex microbial community in their digestive system for food digestion. We wondered how this would influence the content of their saliva. We therefore sampled saliva from five humans and both nose secretions and saliva from six cows and separated the saliva on SDS-PAGE gradient gels and analyzed the major protein bands by LC-MS/MS. The cow saliva was found to be dominated by a few major proteins only, the carbonic anhydrase 6, a pH stabilizing enzyme, and the short palate, lung and nasal epithelium carcinoma-associated protein 2A (SPLUNC2A), also named bovine salivary protein 30kDa (BSP30). This latter protein has been proposed to play a role in local antibacterial response by binding bacterial lipopolysaccharide (LPS) and inhibit bacterial growth, but may instead according to more recent data instead have primarily surfactant activity. Numerous peptide fragments of mucin-5B were also detected in the MS analysis. However, mucins stain poorly by the gel staining solution and they are large and have difficult to enter regular gels why their presence easily are overseen. Interestingly, no major band on gel was detected representing any of the antibacterial proteins indicating that cows may produce them at very low levels not to harm the microbial flora of their digestive system. The nose secretions of the cows primarily contained the odorant protein, a protein thought to be involved in enhancing the sensing of smell by the olfactory receptors to enhance the possibility to quickly sense potential poisonous food components. High levels of secretory IgA was also found in one sample of cow mouth drippings indicating a strong upregulation during an infection. The human saliva we more complex containing both secretory IgA, amylase, carbonic anhydrase 6, lysozyme, histatins and a number of other less abundant proteins.

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization of movements. Their study, like that of any other scientific field, must use specific notions to get to grips with them. This review is therefore organized along a series of notions that are frequently used in motor control, and we will discuss them with particular emphasis on neurological conditions, which may disrupt normal motor functioning. We will start with a short description of the roles of space and time, in which movements take place. Subsequently we will deal with kinematics and kinetics (dynamics) of movements. Then, we will list the inputs to motoneurons (MNs), which, in different forms, convey signals from the central nervous system (CNS) to skeletal muscles and muscle spindles, including central pattern generators (CPGs), sensory inputs and supraspinal descending fiber systems. Some helpers in movement organization will be introduced, such as internal models and neuronal network models. A relatively brief section on sensory-motor learning will follow because learning abilities are required to endow the sensory-motor system with flexibility and adaptability. The major emphasis is placed on neurological processes, which result from genetic modifications, autoimmune diseases, neurodegenerative diseases, infections in the nervous system as well as vascular and traumatic lesions. These neurological diseases lead to a variety of impairments and symptoms, particularly movement derangements including cerebellar ataxia, spasticity, and (other) movement disorders such as Parkinson’s syndromes. The conclusion is that there is no unique top controller that controls ´motor control`.

Over the years, various models have been developed in the stages of the mining process that have allowed predicting and enhancing results, but it is the breakage the variable that connects all the activities of the mining process from the point of view of costs (drilling, blasting, loading, hauling, crushing and grinding). To improve this process, we come up with an idea to develop a breakage prediction model; on the basis of the main variables involved in the drilling and blasting process. For this purpose, we design a computer model based on an Artificial Neuronal Networks (ANN), built by using the most representative variables that come into play with drilling and blasting, such as: the properties of the explosives, the geomechanical parameters of the rock mass, and the design parameters of drilling-blasting. For its experimentation and validation, we have taken the data from a copper mine as reference located in the north of Chile, because of we have the dataset of that ore deposit, which is valid and reliable to evaluate prediction problems based on ANN applied to copper mines. The ANN architecture was of the supervised type, feedforward, with 3 layers and 13 neurons in the only hidden layer, trained with the input data using a dataset with the previously mentioned variables, which then were compared with the breakage results. The model was feed backed in its learning process until it becomes perfected, and is a prediction option that can be used in future blasting of ore deposits with similar characteristics using the same representative variables. Therefore, this is a valid alternative for predicting rock breakage, given that it has been experimentally validated, and has achieved moderately reliable results, providing higher correlation coefficients than traditional models, and with the additional advantage that an ANN model provides, due to its ability to learn and recognize compiled dataset patterns. In this way, using this computer model we can obtain satisfactory results that allow us to predict breakage, providing an alternative for evaluating the costs that this entails.

The extended cleavage specificity of catfish granzyme-like II has been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated by using a panel of recombinant substrates. This serine protease, which has previously been isolated as cDNA from a catfish natural killer-like cell line showed a preference for alanine in the P1 position of the substrate, and for multiple basic amino acids N-terminally of the cleavage site. Using a set of recombinant substrates revealed the enzyme was most active on substrates with an alanine preceded by 3 or 4 basic amino acids in a row, but also showed activity against substrates with two basic amino acids, as well as with two basic amino acids separated by one amino acid just N-terminally of the Ala. The characteristics of this separating amino acid seemed less important, as many different amino acids were accepted in this position, except for proline. The amino acids following the basic amino acids and the P1 Ala residue also appeared to be of major importance for efficient cleavage. The most preferred P1 residue was Ala, and replacing Ala with Gly or Leu resulted in a clear reduction in the cleavage rate. A closely-related zebrafish serine protease (Zebrafish esterase-like) showed a very similar cleavage specificity, indicating an evolutionary conservation of this protease specificity among various fish species. Two catfish serine proteases, originating from NK-like cells, have now been isolated and characterized. One of them is highly specific met-ase with similar characteristics as the mammalian granzyme M. This enzyme may be involved in the induction of apoptosis in virus infected cells, with a potential target in (catfish) caspase 6. In contrast to catfish granzyme -like I, the second enzyme analysed here, doesn’t seem to have a direct counterpart in mammalian NK-cells, and its role in the immune function of catfish NK cells is therefore still not known. However, this enzyme seems to be able to cleave a number of cytoskeletal proteins indicating a separate strategy to induce apoptosis in target cells. Both of these enzymes are very interesting targets for further studies of their roles in catfish immunity, as enzymes with similar specificities have been identified also in zebrafish.

At-home rapid antigen test (RAT) kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are valuable public health tools during the present coronavirus disease (COVID-19) pandemic. They provide fast identification of coronavirus infection, which can help to reduce the transmission rates and burden on the healthcare system. However, they have lower sensitivity when compared with the reverse transcription polymerase chain reaction (RT-PCR) tests. One of the reasons for the lower sensitivity is due to the RAT color indicators being indistinct or invisible to the naked eye after the measurements. For this reason, we propose a systematic approach, through which we investigated anonymously provided at-home RAT kit results by using our in-house open source image processing scripts developed for affordable Raspberry Pi computer and Raspberry Pi HQ camera systems (available at https://github.com/kmiikki/ratcv). Therefore, we aimed at minimizing the human-related analysis errors for such kits. We believe that our framework can contribute to reduced the delayed quarantines of infected individuals and spreading of the current infectious disease.

Background:Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins^® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins^® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN.Case Description:A fifty-one-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted with Walkasins^® and utilized the shoe inserts 8-10 hours/day for more than 1 year. Although, vibration and tactile thresholds were severely impaired at his 1^st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins^® above the ankles.Outcomes:Following Walkasins^® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33% to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 m/sec to 1.5 m/sec. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function.Discussion:Gait and balance improved with the use of the Walkasins^® and participation in the Neuro Wellness Program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins^®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins^®.

To date, several independent methods and algorithms exist exploiting constraint-based stoichiometric models to find metabolic engineering strategies that optimize microbial production performance. Optimization procedures based on metaheuristics facilitate a straightforward adaption and expansion of engineering objectives as well as fitness functions, while being particularly suited for solving problems of high complexity. With the increasing interest in multi-scale models and a need for solving advanced engineering problems, we strive to advance genetic algorithms, which stand out due to their intuitive optimization principles and proven usefulness in this field of research. A drawback of genetic algorithms is that premature convergence to sub-optimal solutions easily occurs if the optimization parameters are not adapted to the specific problem. Here, we conducted comprehensive parameter sensitivity analyses to study their impact on finding optimal strain designs. We further demonstrate the capability of genetic algorithms to simultaneously handle (i) multiple, non-linear engineering objectives, (ii) the identification of gene target-sets according to logical gene-protein-reaction associations, (iii) minimization of the number of network perturbations, and (iv) the insertion of non-native reactions, while employing genome-scale metabolic models. This framework adds a level of sophistication in terms of strain design robustness, which is exemplarily tested on succinate overproduction in Escherichia coli.

In California, water is a perennial concern. As competition for water resources increases due to growth in population, California’s tree nut farmers are committed to improving the efficiency of water used for food production. There is an imminent need to have reliable methods that provide information about the temporal and spatial variability of crop water requirements, which allow farmers to make irrigation decisions at field scale. This study focuses on estimating the actual evapotranspiration and crop coefficients of an almond and pistachio orchard located in Central Valley (California) during an entire growing season by combining a simple crop evapotranspiration model with remote sensing data. A dataset of the vegetation index NDVI derived from Landsat-8 was used to facilitate the estimation of the basal crop coefficient (Kcb), or potential crop water use. The soil water evaporation coefficient (Ke) was measured from microlysimeters. The water stress coefficient (Ks) was derived from airborne remotely sensed canopy thermal-based methods, using seasonal regressions between the crop water stress index (CWSI) and stem water potential (Ystem). These regressions were statistically-significant for both crops, indicating clear seasonal differences in pistachios, but not in almonds. In almonds, the estimated maximum Kcb values ranged between 1.05 to 0.90, while for pistachios, it ranged between 0.89 to 0.80. The model indicated a difference of 97 mm in transpiration over the season between both crops. Soil evaporation accounted for an average of 16% and 13% of the total actual evapotranspiration for almonds and pistachios, respectively. Verification of the model-based daily crop evapotranspiration estimates was done using eddy-covariance and surface renewal data collected in the same orchards, yielding an r² >= 0.7 and average root mean square errors (RMSE) of 0.74 and 0.91 mm day^-1 for almond and pistachio, respectively. It is concluded that the combination of crop evapotranspiration models with remotely-sensed data is helpful for upscaling irrigation information from plant to field scale and thus may be used by farmers for making day-to-day irrigation management decisions.

Benzylsuccinate is generated in anaerobic toluene degradation by radical addition of toluene to fumarate and further degraded to benzoyl-CoA by a beta-oxidation pathway. Using metabolic modules for benzoate transport and activation to benzoyl-CoA and the enzymes of benzylsuccinate beta-oxidation, we established an artificial pathway for benzylsuccinate production in Escherichia coli, which is based of its degradation pathway running in reverse. Benzoate is supplied to the medium, but needs to be converted to benzoyl-CoA by an uptake transporter and a benzoate-CoA ligase or CoA-transferase. In contrast, the second substrate succinate is endogenously produced from glucose under anaerobic conditions, and the constructed pathway includes a succinyl-CoA:benzylsuccinate CoA-transferase that activates it to the CoA-thioester. We present first evidence for the feasibility of this pathway and explore product yields under different growth conditions. Compared to aerobic cultures, the product yield increased more than 1000-fold in anaerobic glucose-fermenting cultures and showed further improvement under fumarate-respiring conditions. An important bottleneck to overcome appears to be product excretion, based on much higher recorded intracellular concentrations of benzylsuccinate, compared to those excreted. While no export system is known for benzylsuccinate, we observed an increased product yield after adding an unspecific mechanosensitive channel to the constructed pathway.

Fatigue-related subchondral bone injury of the third metacarpal/ metatarsal (McIII/ MtIII) bone is a common cause of wastage and welfare concern in racehorses. Better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. Porosity index (PI) of bone is an indirect measure of osseous pore size and number and is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods even with short echo times fails to generate enough signal to assess bone architecture as the water protons are tightly bound. Ultrashort echo time (UTE) sequences aim to increase the amount of signal detected in the equine McIII/MtIII condyle. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD). BMD and PI are inversely correlated in the equine distal Mc/ MtIII with a mean r value of -0.29. The r value is significantly different between fore- and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of the bone and to evaluate PI in horses with and without clinically relevant stress injury.

Iron-containing nickel sulfides, selenides, and sulfoselenides were synthesized via a simple two-step hydrothermal reaction (temperature 160 °C) for their application as electrocatalysts in the oxygen evolution reaction (OER) in an alkaline solution (1 mol L–1 KOH). The study demonstrated that iron-containing nickel cobalt sulfides and selenides exhibit superior OER performance with lower overpotentials compared to iron-free nickel cobalt sulfide and selenide, which highlights the significant role of iron in enhancing OER nickel cobalt electrocatalysts: Fe0.1Ni1.4Co2.9(S0.87O0.13)4, η50 = 318 mV; Fe0.2Ni1.5Co2.8(S0.9O0.1)4, η50 = 310 mV; Fe0.3Ni1.2Co2.5(S0.9O0.1)4, η50 = 294 mV; Fe0.6Ni1.2Co2.5(S0.83O0.17)4, η50 = 294 mV, Fe0.4Ni0.7Co1.6(Se0.81O0.19)4, η50 = 306 mV compared to Ni1.0Co2.1(S0.9O0.1)4, η50 = 346 mV and Ni0.7Co1.4(Se0.85O0.15)4, η50 = 355 mV (all values at current densities η50 of 50 mA cm–2). Furthermore, the iron-containing nickel cobalt sulfoselenide Fe0.5Ni1.0Co2.0(S0.57Se0.25O0.18)4 displayed exceptional OER performance with η50 = 277 mV, surpassing the benchmark RuO2 electrode with η50 = 299 mV. The superior performance of the sulfoselenide was attributed to its low charge transfer resistance (Rct) of 0.8 Ω at 1.5 V vs. the reversible hydrogen electrode (RHE). Moreover, the sulfoselenide demonstrated remarkable stability, with only a minimal increase in overpotential (η50) from 277 mV to 279 mV after a 20 h chronopotentiometry test. These findings suggest that trimetallic iron, nickel and cobalt sulfide, selenide and especially sulfoselenide materials hold promise as high-performance, cost-effective, and durable electrocatalysts for sustainable OER reactions. This study provides a valuable approach for the development of efficient electrocatalytic materials, contributing to the advancement of renewable energy technologies.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

1) Background: Several studies have shown the benefit of drawing when learning anatomy. Virtual Reality (VR) also appears to be useful to increase the understanding of the location of anatomical structures. This study aims to describe how students in an Operating Room Nursing (OR nursing) master study program perceive the benefit of active learning methods, including drawing and the use of VR. 2) Methods: We combined these two methods in a class of 29 students. 38 half-finished drawings of anatomical structures were made. The students were to complete these during lectures with guidance from the teacher. The students also attended a two-hour VR session where they were to find various anatomical structures. A paper questionnaire was applied to evaluate the teaching program. Data were analyzed statistically. 3) Results: The students highly appreciated these learning methods. They reported that drawing made them work more actively during lectures and increased their learning outcome. They also perceived that the use of VR technology increased their understanding of the location of anatomical structures. 4) Conclusion: The combination of drawing and VR technology may be of benefit to OR Nursing students when learning anatomy by both increasing student activity and learning outcomes.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants-small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.

This paper presents a comparison between a kite model with a constant-length tether and a model based on a system identification algorithm. The concept of system identification is applied to predict the uncertainties related to the variation of the wind speed and the shape deformation of the tethered membrane wing during flight. A pole-placement controller is used to ensure that the kite follows the planned flight path. Thus, we can determine the required locations of the closed loop poles, and then enforce them by changing the controller's gains in real-time. The capability of the system identification algorithm to recognize sudden changes in the dynamic model, and the ability of the controller to stabilize the system in the presence of such changes are confirmed. Furthermore, the system identification algorithm is applied to determine the parameters of a kite with variable-length tether used in a flight test of the 20 kW kite power system of TU Delft. Experimental data of this test were compared with the system identification results in real-time and significant changes were observed in the parameters of the dynamic model which heavily affect the resulting response.

Drones are being used more and more frequently and in various ways to attack people and critical infrastructures, which increases their level of danger and makes early detection and risk assessment even more difficult. There is no ultimate drone sensor. Rather, drones can only be effectively detected, if suitable sensor technologies are integrated within a system. Among the best suited sensorics for this purpose are radar and optical sensors, because the advantage of the radar, given by the long detection range, can be well combined with the additional visual-based information gained from a camera in the mid- and short-range, where usually the radar fails detecting micro drones. In this paper, a modular drone detection and assistance system MODEAS is presented, which can be used to automatically detect and track drones within a range up to some kilometers on the sky, but also in complex urban environments, where buildings and vegetation offer a perfect background for camouflage. The system provides an early detection of flying objects as potential drones, when those are not at all or only as small dots visible for the human eye. Main strengths of the system are the robust AI detection to differentiate such an object against clutter (birds, clouds) and its further classification by model and payload recognition, the latter aspect being considered as an indication of dangerousness. Moreover, once a drone is detected, the system follows it automatically, precisely and smoothly with a high-resolution pan-tilt-camera, measuring the distance to the sensor station with a laser rangefinder, compute the geocoordinates and visualize them live on a map. To improve the precision of the detection, a multisensorial fusion of all sensor detections is performed. Furthermore, alarms may be generated when a drone enters a restricted area.

Background: Misconceptions and knowledge gaps about antibiotic use contribute to inappropriate antibiotic use and antimicrobial resistance. Aim: Identifying and prioritizing misconceptions and knowledge gaps about antibiotic use from a healthcare professionals’ perspective. Methods: A modified Delphi study of two rounds with an expert meeting. A literature search was conducted to create statements about misconceptions and knowledge gaps about antibiotic use. These were rated by healthcare professionals from five EU countries representing general practice, out-of-hour services, nursing homes, and pharmacies. Consensus was achieved if ≥80% of the participants rated 4+ on a five-point Likert scale during the second Delphi round. Results. In total, 44 misconceptions were identified through the literature search within four themes: 1) antimicrobial resistance in general, 2) use of antibiotics in general, 3) use of antibiotics for respiratory tract infections, and 4) use of antibiotics for urinary tract infections. Consensus was reached for more than half of the statements within each setting. Conclusions. Experts from different settings and nationalities acknowledge that multiple misconceptions and knowledge gaps can contribute to inappropriate use of antibiotics in the community. These results provide valuable information to use in educational campaigns for patients and healthcare professionals to improve the use of antibiotics.

Metal-organic frameworks (MOFs) are investigated for the oxygen evolution reaction (OER) due to their structure diversity, high specific surface area, adjustable pore size and abundant active sites. However, the poor conductivity of most MOFs restricts this application. Herein, through a facile one-step solvothermal method, the Ni-based pillared metal-organic framework [Ni2(BDC)2DABCO] (BDC = 1,4-benzenedicarboxylate, DABCO = 1,4-diazabicyclo[2.2.2]octane), its bimetallic nickel-iron form [Ni(Fe)(BDC)2DABCO] and their modified Ketjenblack (mKB) composites were synthesized and tested towards OER in an alkaline medium (KOH 1 mol L–1). A synergistic effect of the bimetallic nickel-iron MOF and the conductive mKB additive enhance the catalytic activity of the MOF/mKB composites. All MOF/mKB composite samples (7, 14, 22, 34 wt.% mKB) indicated much higher OER performances than the MOFs and mKB alone. The Ni-MOF/mKB14 composite (14 wt. % of mKB) demonstrated an overpotential of 294 mV at a current density of 10 mA cm–2 and Tafel slope of 32 mV dec–1, which is comparable with commercial RuO2 commonly used as a benchmark material for OER. The catalytic performance of Ni(Fe)MOF/mKB14 (0.57 wt% Fe) was improved further to an overpotential of 279 mV at a current density of 10 mA cm–2. The low Tafel slope of 25 mV dec–1 as well as a low reaction resistance due to electrochemical impedance spectroscopy (EIS) measurement confirm the excellent OER performance of the Ni(Fe)MOF/mKB14 composite. For practical applications, the Ni(Fe)MOF/mKB14 electrocatalyst was impregnated into commercial nickel foam (NF), where overpotentials of 247 and 291 mV at current densities of 10 and 50 mA cm–2, respectively, were realized. The activity was maintained for 30 h at the applied current density of 50 mA cm–2. The electrocatalytic system consisting of earth-abundant Ni and Fe metals only would be attractive for the development of efficient, practical and economical energy conversion materials for efficient OER activity.

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.

Porous ceramics can be realized by different methods and are used for manifold applications, like cross-flow-membranes or wall-flow-filters, porous burners, solar receivers, structural design elements or catalytic supports. Within this paper three different alternative process routes are presented, which can be used to manufacture porous ceramic components with different properties or even graded porosity. The first process route bases on additive manufacturing (AM) of macro porous ceramic components, the second on AM of a polymeric template, which is used to manufacture porous ceramic components via replica technique. Finally, the third process route bases on an AM technology, which allows the manufacturing of multi-material or multi-property ceramic components, like components with dense and porous volumes in one complex shaped component.

In the design of educational robots, it seems undecided whether robots should show social behaviors and look human-like or that such cues are indifferent to learning. We conducted an experiment with different designs of social robots, rehearsing the multiplication tables with primary school children in Hong Kong. Results show that affective bonding tendencies may occur but did not significantly contribute to the learning progress of these children, perhaps due to the short interaction period. Nonetheless, 5 minutes of robot tutoring improved their scores with about 30% and only for a few challenged children, performance dropped. We discuss that topics such as teaching language skills may be fostered by human likeness in appearance and behaviors but that for STEM-related subjects, the social aspects of robots hardly matter.

For orthopaedic applications, additive manufactured (AM) porous scaffolds made of absorbable metals like magnesium, zinc or iron are of particular interest. They do not only offer the potential to design and fabricate bio-mimetic or rather bone equivalent mechanical properties, they also do not need to be removed in further surgery. Located in a physiological environment, scaffolds made of absorbable metals show a decreasing Young’s modulus over time, due to product dissolution. For WE43 scaffolds, during the first days an increase of the smeared Young's modulus can be observed, which is mainly attributed to a forming substrate layer of degradation products on the struts surfaces. In this study the influence of degradation products on the stiffness properties of metallic scaffolds is investigated. For this, analytical calculations and finite element simulations are performed to study the influence of the substrate layer thickness and Young's modulus for single struts and for a new scaffold geometry with adapted polar f2cc,z unit cells. The finite element model is further validated by compression tests on AM scaffolds made from Zn1Mg. The results show, that even low thicknesses and Young's moduli of the substrate layer increases significantly the smeared Young's modulus under axial compression.

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identifying and characterizing molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of transcriptomic data focusing on two TF genes, ZNF385D, HAND2, whose polymorphisms reportedly associate with carotid atherosclerosis. Gene expression data were measured from pieces of carotid endarterectomy of hypertensive patients each paired with one sample of distant macroscopically intact tissue. TF networks were reconstructed for ZNF385D and HAND2 and their association with carotid atheroma progression examined using gene-set enrichment analysis with high statistical significance (p<6.95e-7) suggesting involvement of expression quantitative loci (eQTL). Examination of the regulation and correlation patterns suggests high clinical and interventional impacts of the two TF genes on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Amyloid β-peptide (Aβ) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of Aβ oligomerization in neurons still need to be revealed. Förster Resonance Energy Transfer (FRET) is a simple but effective way to study molecular interactions. Here we use a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detect Aβ42 oligomerization in primary neurons. The neurons were incubated with fluorescently labelled Aβ42 in the cell culture medium for 24 hours. Aβ42 were internalized and oligomerized into the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of Aβ42 were significantly higher than for Aβ40. These findings provide a better understanding of Aβ42 oligomerization in neurons.

Actively controlling the camber angle to improve energy efficiency has recently gained interest due to the importance of reducing energy consumption and the driveline electrification trend that makes cost-efficient implementation of actuators possible. To analyse how much energy that can be saved with camber control, the effect of changeing the camber angles on the forces and moments of the tyre under different driving conditions should be considered. In this paper, Magic Formula tyre models for combined slip and camber are used for simulation of energy analysis. The components of power loss during cornering are formulated and used to explain the influence that camber angles have on the power loss. For the studied driving paths and the assumed driver model, the simulation results show that active camber control can have considerable influence on power loss during cornering. Different combinations of camber angles are simulated, and a camber control algorithm is proposed and verified in simulation. The results show that the camber controller has very promising application prospects for energy-efficient cornering.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Background: Physical activity is recommended to mitigate the incidence of obesity, but delivery of community wide initiatives is cumbersome. The challenges met by such programs are magnified when implementation transpires in the remote villages of Alaska. To overcome the difficulty of this challenge in the Arctic, the Skiku/AK Nordic cross-country skiing program was developed. The objective of this study was to evaluate whether access to Skiku/AK Nordic program would promote physical activity levels that met the daily recommendations for physical activity in Alaska Native children. Methods: Eight children (4 females and 4 males; 10±2 years/age) were recruited from Kaktovik, Alaska for participation in this study. Expert coaches and staff provided one week of cross-country ski instruction and access to ski equipment. Physical activity was monitored using ActiGraph GT3X+ accelerometers. Data collected from the devices was then downloaded and analyzed using ActiLife software. Results: The participants expended ~586 calories/day devoted to physical activity. Light and moderate physical activity was 68±38 minutes/day and 447±248 minutes/day, respectively. Conclusions: Delivery of the Skiku/AK Nordic program promoted favorable levels of physical activity in Alaska Native children. Further research is needed to assess the longitudinal and seasonal effectiveness of the Skiku/AK Nordic program.

The construction of different roads, such as freeways, highways, major roads or minor roads must be accompanied by constant monitoring and evaluation of service delivery. Pavements are generally assessed by engineers in terms of the smoothness, surface condition, structural condition and surface safety. Pavement assessment is often conducted using the qualitative indices such as international roughness index (IRI), pavement condition index (PCI), structural condition index (SCI) and skid resistance value (SRV), which are used for smoothness assessment, surface condition assessment, structural condition assessment, and surface safety assessment, respectively. In this paper, Tehran-Qom Freeway in Iran has been selected as the case study and its smoothness and pavement surface conditions are assessed. At 2-km intervals, a 100-meter sample unit is selected in the slow-speed lane (totally, 118 sample units). In these sample units, the PCI is calculated after a visual inspection of the pavement and the recording of distresses. Then, in each sample unit, the average IRI is computed. The purpose of this study is to provide a method for estimating PCI based on IRI. The proposed theory was developed by Random Forest (RF), and Random Forest optimized by Genetic Algorithm (RF-GA) methods and these methods were validated using correlation coefficient (CC), scattered index (SI), and Willmott’s index of agreement (WI) criteria. The proposed method reduces costs, saves time and eliminates the safety risks.

The high environmental impact of conventional methods of cooling and heating has increased the need for renewable energy deployment for covering thermal loads. Towards that direction, the proposed system aims at offering an efficient solar powered alternative, coupling a zeolite-water adsorption chiller with a conventional vapor compression cycle. The system is designed to operate under intermittent heat supply of low-temperature solar thermal energy (<90 °C) provided by evacuated tube collectors. A prototype was developed and tested in cooling mode operation. The results of separate components testing showed that the adsorption chiller was operating efficiently, achieving a maximum coefficient of performance (COP) of 0.65. With respect to the combined performance of the system, evaluated on a typical week of summer in Athens, the maximum reported COP was approximately 0.575, mainly due to the lower driving temperatures at a range of 75 °C. The corresponding mean energy efficiency ratio (EER) obtained was 5.8.

Abstract Introduction Exercise is an effective component in rehabilitation of a range of chronic conditions. There is a growing interest in the use of exercise-based nature interacted rehabilitation (EBNIR), but an overview of current evidence is missing. To provide an informed base for future work within this field of EBNIR, the objective of this scoping review was to map existing exercise-based rehabilitation interventions conducted with incidental or intentional nature interaction focusing on its populations, types of outcomes, and theoretical rationale for people with physical and mental disabilities. Methods This scoping review identified peer-reviewed publications, registered upcoming trials and grey literature. To map all available knowledge, we performed a comprehensive search of selected databases (MEDLINE; EMBASE; CINAHL; Cochrane; Web of Science; Pedro) from inception to October 2022. Data was synthesised in a thematic presentation guided by TIDieR, supplemented by a checklist developed for this study accounting nature incidental or intentional interaction by measuring all nature elements implemented in the intervention. Results Twelve studies including 856 participants met the inclusion criteria. 11 were completed trials and 1 was registered in clinicaltrials.gov to be run in 2023. A total of 856 patients were enrolled in the 12 studies (range 18-262, median 50). The included studies were different in terms of design (observational n=4, qualitative n=1, RCT=7), intervention dosage and frequency, control intervention, diagnosis, number of patients, and outcomes included. The used exercise-based interventions consisted of outdoor walks, neck exercises and surfing interventions in patients with physical or mental health conditions. The interventions were incidental or intentional interacted with nature to a varying degree. Conclusion This scoping review presents an overview of limited and diverse evidence within the field of exercise-based rehabilitation incidental or intentional interacting with nature, in patients with physical or mental health conditions. Our review provides an overview that will be helpful in the design of future EBNIR trials.

Energy system models have become indispensable to shape future energy systems by providing insights into different trajectories. However, sustainable systems with high shares of renewable energy are characterized by growing cross-sectoral interdependencies and decentralized structures. To capture important properties of increasingly complex energy systems, sophisticated and flexible modelling tools are needed. At the same time open science becomes increasingly important in energy system modelling. This paper presents the Open Energy Modelling Framework (oemof) as a novel approach in energy system modelling, representation and analysis. The framework forms a toolbox to construct comprehensive energy system models and has been published open source under a free license. With a collaborative development based on open processes the framework seeks for a maximum level of participation and transparency to facilitate open science principles in energy system modelling. Based on a generic graph based description of energy systems it is well suited to flexibly model complex cross-sectoral systems and incorporate various modelling approaches. This makes the framework a multi-purpose modelling environment for modelling and analyzing different systems ranging from an urban to a transnational scale.

: Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metallopro-teinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "biorector," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and pro-liferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wound. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

This paper provides the state of the art of data science in economics. Through a novel taxonomy of applications and methods advances in data science are investigated. The data science advances are investigated in three individual classes of deep learning models, ensemble models, and hybrid models. Application domains include stock market, marketing, E-commerce, corporate banking, and cryptocurrency. Prisma method, a systematic literature review methodology is used to ensure the quality of the survey. The findings revealed that the trends are on advancement of hybrid models as more than 51% of the reviewed articles applied hybrid model. On the other hand, it is found that based on the RMSE accuracy metric, hybrid models had higher prediction accuracy than other algorithms. While it is expected the trends go toward the advancements of deep learning models.

The article describes the study of the properties of polytetrafluoroethylene, modified using natural layered silicates—serpentinite. It is shown that the introduction of a small amount of layered silicates significantly increases the tribological characteristics of the material. The additional introduction of magnesium nano-spinels facilitated the formation of an intercalated polymer-silicate nanocomposite.

The COVID-19 is a highly contagious viral infection which played havoc on everyone's life in many different ways. According to the world health organization and scientists, more testing potentially helps governments and disease control organizations in containing the spread of the virus. The use of chest radiographs is one of the early screening tests to determine the onset of disease, as the infection affects the lungs severely. This study will investigate and automate the process of testing by using state-of-the-art CNN classifiers to detect the COVID19 infection. However, the viral could of many different types; therefore, we only regard for COVID19 while the other viral infection types are treated as non-COVID19 in the radiographs of various viral infections. The classification task is challenging due to the limited number of scans available for COVID19 and the minute variations in the viral infections. We aim to employ current state-of-the-art CNN architectures, compare their results, and determine whether deep learning algorithms can handle the crisis appropriately. All trained models are available at https://github.com/saeed-anwar/COVID19-Baselines

This study introduces an alternative to the existing methods for measuring ocean currents based on a recently developed technology. The SailBuoy is an unmanned surface vehicle powered by wind and solar panels that can navigate autonomously to predefined way-points and record velocity profiles using an integrated downward-looking Acoustic Doppler Profiler (ADCP). Data, collected on two validation campaigns, shows a satisfactory correlation between the SailBuoy current records and traditional observation techniques such as bottom mounted and moored current profilers and moored single-point current meter. While the highest correlations were found in tidal signals, strong current, and calm weather conditions, low current speeds and varying high wave and wind conditions reduced correlation considerably. Filtering out some events with high sea surface roughness associated with high wind and wave conditions may increase the SailBuoy ADCP listening quality and lead to better correlations. Not yet resolved is a systematic offset between the measurements obtained by the SailBuoy and the reference instruments of ± 0.03 m/s. Possible reasons are discussed to be the differences between instruments (various products) as well as changes in background noise levels due to environmental conditions.

1) Background: Ultrasound-based strain imaging is now available in several ultrasound (US) scanners. Strain ratio (SR) can be used to quantify strain recorded simultaneously in two different user-selected areas, ideally exposed to the same amount of stress. The aim of this study was to evaluate SR variability when assessed in an in-vitro setup with a tissue-mimicking phantom, on resected tissue samples and in live tissue scanning with endoscopic applications. 2) Material and methods: Retrospective analysis of SR for quantification of elastic contrasts in a tissue-mimicking phantom containing four homogenous inclusions, in 38 resected bowel wall lesions and in 48 focal pancreatic lesions examined in vivo. Median SR and the inter-quartile range (IQR) was calculated on all external and endoscopic US-applications. The IQR/median provides a measure of the SR variability focusing on the two percentiles of the data closest to the median value. 3) Results: The overall variability of SR was lowest in a tissue-mimicking phantom (mean QR/median SR: 0.07). In resected bowel wall lesions representing adenomas, adenocarcinomas or Crohn lesions, the variability increased (mean IQR/Median: 0.62). During an endoscopic examination of focal pancreatic lesions in vivo, the variability increased further (mean IQR/Median: 2.04). 4) Conclusion: SR variability increased when assessed on different targets with growing heterogeneity and biological variability as one moved from homogeneous media to live tissues and endoscopic application. This may indicate a limitation for the accuracy SR evaluation in clinical applications.

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by qRT-PCR, and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabil-ities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions on migration characteristics. Sclerostin expres-sion was evaluated in clinical cases by immunohistochemistry at the OSCC jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The re-sults presented are the first data suggesting a possible involvement of sclerostin in the bone inva-sion process of OSCC, which needs to be further investigated

Technological advancements in the Internet of Things (IoT), unmanned aerial vehicles (UAVs), and novel technological tools have transformed disaster management practices from localized approaches to a global framework. These innovations necessitate a unified understanding and application of diverse methodologies at an international level, ensuring they are accessible and operational across different sectors. This integration is crucial not only for technical personnel but also for medical teams, who play a pivotal role in disaster response and management. By fostering a comprehensive grasp of these methods, we can enhance coordination, efficiency, and effectiveness in addressing disasters on a global scale. The authors aimed to provide a comprehensive overview of emerging techniques that are driving shifts in strategic approaches and treatment technologies. Recognized as a domain of continuous research and development, this overview, by necessity, remains an incomplete snapshot of an evolving field. It highlights the dynamic nature of technological and strategic advancements, underscoring the importance of ongoing investigation and innovation to stay abreast of current trends and future directions. The article also highlights the importance of international collaboration beyond societal and national boundaries A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Studies of mast cell biology is dependent on relevant and validated in vitro models. We here present detailed information concerning the phenotype of both freshly isolated human skin mast cells (MCs), and of in vitro cultures of these cells that was obtained by analyzing their total transcriptome. Transcript levels of MC-related granule proteins and transcription factors were found to be remarkably stable over a 3-week culture period. Relatively modest changes were also seen for important cell surface receptors including the high affinity receptor for IgE, FCER1A, the low affinity receptor for IgG, FCGR2A, and the receptor for stem cell factor, KIT. FCGR2A was the only Fc receptor for IgG expressed by these cells. Comparisons of the present transcriptome against previously reported transcriptomes of mouse peritoneal MCs and mouse bone marrow derived MCs (BMMCs) revealed both similarities and major differences. Strikingly, cathepsin G was the most highly expressed granule protease in human skin MCs, in contrast to the almost total absent of this protease in both mouse MCs. Transcript levels for the majority of cell surface receptors were also very low compared to the granule proteases in both mouse and human MCs, with a difference of almost two orders of magnitude. An almost total absence of T cell granzymes was observed in human skin MCs, indicating that granzymes have no or only a minor role in human MC biology. Ex vivo skin MCs expressed high levels of selective immediate early genes and transcripts of heat-shock proteins. In validation experiments, we determined that this expression was an inherent property of the cells and not the result of the isolation process. Three to four weeks in culture results in an induction of cell growth related genes accompanying their expansion by 6-10-fold, which increases the number of cells for in vitro experiments. Collectively, we show that cultured human skin MCs resemble their ex vivo equivalents in many respects and are a more relevant in vitro model compared to mouse BMMCs for studies of MC biology, in particular human MC biology.

Parts of shotgun cartridges are a significant source of plastic litter in the marine environment. Empty cartridge shells may not be picked up by the hunter who fired them, and plastic wads that serve to separate the propellant from the shot load, are lost down-range when a shot is fired. Such litter items constitute a cosmetic and aesthetic problem on coastlines and may cause harm to marine animals and in the later stages of decomposition break down into harmful micro plastic particles. There exists no reliable estimate of the global exposure of marine ecosystems to this plastic source. However, in some countries it has been subject to closer examination, including for example, Denmark where the annual contribution of plastic wads into marine systems was estimated to 600,000 pieces (c2 tonnes), and the accumulated density of washed-up items (both wads and shells) was 3.7 items per 100 m coastline. Increasing awareness of this problem has caused scientists, hunters’ communities and governments to suggest altered practice including transition to the use of biodegradable cartridge components, first and foremost wads as this item is invariable lost during hunting. Several manufacturers provide shotgun cartridges containing biodegradable wads based on different types of materials, including fibers and various types of plastics, for example PVAL (poly(vinyl alcohol)) and PHA (polyhydroxyalkanoate). In this paper, we review the most recent literature on the amounts and related environmental hazards of plastic dispersed from hunting ammunition into marine ecosystems. We summarize the market availability of shotgun cartridges with biodegradable wads and discuss chemical, technical, economical and legal aspects of a transition to the use of such products.

Abstract: Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gut through the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and 3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lack of fiber affects the production of SCFAs and the vulnerability of the co-lon. Additionally, the involvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations in luminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs were applied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion of GLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of die-tary fiber significantly decreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, and butyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In the DSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severity was independent of FFAR2 and FFAR3 signaling.

Advanced ceramics are recognized as key enabling materials possessing combinations of properties not achievable in other material classes. They are characterized by very high thermal, chemical and mechanical resistance and also usually have a lower density than metals. These properties predestine ceramics for many different applications, especially space applications.In the aerospace sector aerospike nozzles promise performance and application advantages compared to classic bell nozzles but are also inherently more complex to manufacture due to their shape. AM methods drastically simplify or even enable the fabrication of those complex structures while minimising the number of individual parts. The applicability of ceramic AM (“CerAMfacturing”) on rocket engines and especially nozzles is consequently investigated in the frame of the “MACARONIS” project, a cooperation of the Institute of Aerospace Engineering at Technische Universität Dresden and the Fraunhofer Institute for Ceramic Technologies and Systems (IKTS) in Dresden. The goal is to develop novel large size aerospike thrust nozzles including areas of highest resolution and fineness. Finding a suitable AM process that enables the realisation of both aspects is extremely challenging. One possibility could be the hybridization of shaping methods, in that case CerAM VPP (ceramic additive manufacturing via vat photopolymerization) and CerAM FFF (ceramic additive manufacturing via fused filament fabrication) in combination with sinter joining. This contribution focuses on the high resolution CerAM VPP process, in particular the development, characterization and testing of a new photoreactive Al₂O₃ suspension validated by AM of novel aerospike nozzles.

In our study we investigated the additive manufacturing (AM) of ceramic-based Functionally Graded Materials (FGM) by the direct AM technology Thermoplastic 3D-Printing (T3DP). Zirconia components with a varying microstructure were additively manufactured by using thermoplastic suspensions with different contents of pore forming agents (PFA) and were co-sintered defect-free. Different materials were investigated concerning their suitability as PFA for the T3DP process. Different zirconia-based suspensions were prepared and used for AM of single- and multi-material test components. All samples were sintered defect-free and in the end we could realize a brick wall-like component consisting of dense (<1% porosity) and porous (approx. 5% porosity) zirconia areas to combine different properties in one component. The T3DP opens the door to AM of further ceramic-based 4D-components like multi-color or multi-material, especially multi-functional components.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

The traditional understanding of brain function has predominantly focused on chemical and electrical processes. However, new research in fruit fly (Drosophila) binocular vision reveals ultrafast photomechanical photoreceptor movements significantly enhance information processing, thereby impacting a fly's perception of its environment and behaviour. The coding advantages resulting from these mechanical processes suggest that similar physical motion-based coding strategies may affect neural communication ubiquitously. The theory of neural morphodynamics proposes that rapid biomechanical movements and microstructural changes at the level of neurons and synapses enhance the speed and efficiency of sensory information processing, intrinsic thoughts, and actions by regulating neural information in a phasic manner. We propose that morphodynamic information processing evolved to drive predictive coding, synchronising cognitive processes across neural networks to match the behavioural demands at hand effectively.

Each year in March, adherents of the Bahá’í faith abstain from eating and drinking from sunrise to sunset for 19 days. Thus, Bahá’í fasting (BF) can be considered as a form of daytime dry fasting. We tested if BF decreases energy expenditure after a meal and improves anthropometric measures, and systemic and tissue-level metabolic parameters. This was a self-controlled cohort study with 11 healthy men. We measured anthropometric parameters, metabolic markers in venous blood, and pre- and postprandial energy metabolism at systemic (indirect calorimetry) and tissue (adipose tissue and skeletal muscle microdialysis) level, both before and during BF. During BF, we found reduced body weight, body mass index, body fat and blood glucose. Postprandial increase in energy expenditure was lower, diet-induced thermogenesis tended to be lower. In adipose tissue, perfusion, glucose supply and lipolysis were increased. In skeletal muscle, tissue perfusion did not change. Glucose supply and lipolysis were decreased. Glucose oxidation was increased, indicating an improved insulin sensitivity. BF may be a promising approach to losing weight and improving metabolism and health. However, outside the context of religiously-motivated fasting, skipping a meal rather in the evening (dinner cancelling) might be recommended, as metabolism appears to be reduced in the evening.

The total enthalpies of the 16 different spin configurations that can be realized in the unit cell of the archetype spin crossover complex [Fe(phen)₂(NCS)₂] (phen=1,2-phenanthroline) were calculated applying periodic density functional theory combined with the Hubbard model and the Grimme-D2 dispersion correction (DFT+U/D2). The obtained enthalpy differences between the individual spin configurations were used to determine spin couplings of an Ising-like model and subsequent Monte Carlo simulations for this model allowed to estimate the phenomenological interaction parameter Г of the Slichter-Drickamer model, which is commonly used to describe the cooperativity of the spin transition. The calculational procedure described here, which led to an estimate of about 3 kJ/mol⁻¹ for Г, in good agreement with experiment, may be used to predict from first principles how modifications of spin crossover complexes can change the character of the spin transition from gradual to abrupt and vice versa.

Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms generally referred as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared sleep behavior at three different time points: pre-COVID-19, post-COVID-19 at initial presentation and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients, whilst 11% experienced moderate disease. Initial presentation occurred at a median of 20.4 weeks (6 weeks - 14 months) after infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82+8.7 points) to post-COVID-19 (49.40+8.3 points; p=&lt;0.01). The score then normalized at re-presentation (46.98+7.8; p=0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data show that children and adolescents with long COVID often suffer from sleep disturbance. For most children and adolescents these sleep disorders decreased over time without further medical intervention, aside from a basic sleep consultation.

The paper analyses the national DK-model Hydrological Information and Prediction (HIP) system and HIP portal viewed as a ‘Digital Twin’ and how the introduction of real-time dynamic updating of the DK-model HIP simulations can give room for plug-in sub-models with real-time boundary conditions made available from a HIP portal. The possible feedback to a national real-time risk knowledge base during extreme events (flooding and drought) is also discussed. Under climate change conditions, Denmark is likely to experience more rain in winter, more evapotranspiration in summer, intensified cloudbursts, drought, and sea level rise. These challenges have been addressed as part of the Joint Governmental Digitalization Strategy 2016-2020 for better use and sharing of public data about the terrain, water, and climate to support climate adaptation, water management, and disaster risk reduction. This initiative included the development of a new web-based data portal (HIP portal) developed by the Danish Agency for Data Supply and Infrastructure (SDFI). GEUS delivered 5 terra-byte of hydrological model data to the portal with robust calibration methods and hybrid Machine Learning (ML) being key parts of the deliverables. The paper discusses the challenges and potentials of further developing the HIP Digital Twin with ‘plug-in Digital Twins’ for local river basins including feedback to the national level.

Lactobacillus plantarum is a bacterium with promising applications to the food industry and agriculture and probiotic properties. So far, bacteriophages of this bacterium have been moderately addressed. We examined the morphology and diversity of five new L. plantarum phages via transmission electron microscopy, whole genome shotgun sequencing and in silico protein predictions. Moreover, we looked into their phylogeny and their potential genomic similarities to other complete phage genome records through extensive nucleotide and protein comparisons. The five phages share a high degree of similarity among them and belong to the family Myoviridae. They have a long genome of 137.973-141.344 bp, a G/C content of 36,3-36,6% that is quite distinct from their host’s, and, surprisingly, seven to 15 tRNAs. Only an average 35/174 of their predicted genes were assigned a function. Overall, the comparative analyses unraveled considerable genetic diversity for our five L. plantarum phages. Hence, the new genus “Semelevirus” was proposed, which comprises exclusively the five phages. This novel lineage of Lactobacillus phages provides further insight into the genetic heterogeneity of phages infecting Lactobacillus sp. Our results on Lactobacillus phages have a potential value for the development of anti-phage strategies as well as for the manipulation of L. plantarum fermentations.

The effect of river fronts on oil slick transport has been demonstrated using high resolution forcing models and a fully fledged oil drift model, OpenOil. The model system is used to simulate the 2010 DeepWater Horizon oil spill. Metocean forcing data are taken from the GoM-HYCOM 1/50° ocean model with realistic river input and ECMWF global forecast products of wind and wave parameters with 1/8° resolution. The simulations are initialized from satellite observations of the surface oil patch. OpenOil includes most of the relevant processes, such as emulsification, evaporation, wave entrainment, stranding and droplet formation. The model takes account of the actual oil type and properties, using the ADIOS oil weathering database of NOAA. The effect of using a newly developed parameterization for oil droplet size distribution is studied and compared to a traditional algorithm. Although the algorithms provide different distributions for a single wave breaking event, it is found that the net difference after long simulations is negligible, indicating that the outcome is robust regarding the choice of parameterization. That indicates that the wave entrainment, vertical mixing and re-surfacing mechanisms that are part of OpenOil are more important for determining the final droplet size spectrum than the spectrum prescribed for individual wave breaking events. In both cases, the size of the droplets controls how much oil is present at the surface and hence are subject to wind and Stokes drift. The effect of removing river outflow in the ocean model is investigated in order to showcase effects of river induced fronts on oil spreading. A consistent effect on the amount and location of stranded oil is found, and considerable impact of river induced fronts is seen on the location of the surface oil patch. During a case with large river outflow (May 20-27, 2010), the total amount of stranded oil is reduced by about 50% in the simulation with no river input. The results compares well with satellite observations of the surface oil patch.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of circulating tumour cells (CTCs) on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45- CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median DFS of 3.3 vs. 9.2 months and a median CSS of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 developed distant metastases (DM) and 29 cases isolated local recurrence (ILR) as first event. All patients with CTCs experienced DM. pN-status and histological grade &gt;2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. The impact of CTCs was comparable to that of histopathological risk factors and exceeded the effect size of other preoperative parameters. Thus, preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.

Biobanks linked to electronic health records provide a rich data resource for health-related research. With the establishment of large-scale infrastructure, the availability and utility of data from biobanks has dramatically increased over time. As more researchers become interested in using biobank data to explore a diverse spectrum of scientific questions, resources guiding the data access, design, and analysis of biobank-based studies will be crucial. The first aim of this review is to characterize the types of biobanks that are discussed in the recent literature and provide detailed descriptions of specific biobanks including their location, size, data access, data linkages and more. The development and accessibility of large-scale biorepositories provide the opportunity to accelerate agnostic searches, new discoveries, and hypothesis-generating studies of disease-treatment, disease-exposure and disease-gene associations. Rather than spending time and money designing and implementing a single study with pre-defined objectives, researchers can use biobanks’ existing data-rich resources to answer scientific questions as quickly as they can analyze them. While the data are becoming increasingly available, additional thought is needed to address issues related to the design of such studies and analysis of these data. In the second aim of this review, we discuss statistical issues related to biobank research in general including study design, sampling strategy, phenotype identification, and missing data. These issues are illustrated using data from the Michigan Genomics Initiative, UK Biobank, and Genes for Good. We summarize the current body of statistical literature aimed at addressing some of these challenges and discuss some of the standing open problems in this area. This work serves to complement and extend recent reviews about biobank-based research and aims to provide a resource catalog with statistical and practical guidance to researchers pursuing biobank-based research.

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p &lt; 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.