Using the unique combination of atomically resolved atom probe tomography (APT) and volume averaged neutron (resonance) spin echo (NRSE and NSE) experiments, the influence of nano-scaled clusters on the spin relaxation in spin glasses was studied. For this purpose, the phase transition from the paramagnetic phase to the spin glass phase in a Fe-Cr spin glass with a composition of Fe_17.8Cr_82.2 was studied in detail by means of NRSE. The microstructure was characterised by APT measurements, which show local concentration fluctuations of Fe and Cr on a length scale of 2 to 5 nm, which lead i) to the coexistence of ferro- and anti-ferromagnetic clusters and ii) a change of the magnetic properties of the whole sample, even in the spin glass phase, where spins are supposed to be randomly frozen. We show that a generalized spin glass relaxation function, which was successfully used to describe the phase transition in diluted spin glasses, can also be used for fitting the spin dynamics in spin glasses with significant concentration fluctuations.

Organised hiking and trekking tours are promoted by many providers in adventure travel. Such guided tours shall be engaging for the tourists and evoke positive attitudes towards enjoying nature. We present the Trekking Engagement Profile as a tool to evaluate engagement factors of such guided tours, based on engagement research performed in a different domain, namely evaluating engagement in museums and science centres. This tool shall strengthen guides’ soft skills and enable them to increase engagement during an ongoing arrangement. For instance, the Trekking Engagement Profile can be applied when tourists indicate that the quality of a guided tour is not entirely to their liking. We show the viability of using the Trekking Engagement Profile in a small study with guides and participants of trekking tours offered by the Norwegian Trekking Association. Further, we offer guidance and charts to promote its practical use.

Meixner's historical remark in 1969 "... it can be shown that the concept of entropy in the absence of equilibrium is in fact not only questionable but that it cannot even be defined...." is investigated from today's insight. Several statements --such as the three laws of phenomenological thermodynamics, the embedding theorem and the adiabatical uniqueness-- are used to get rid of non-equilibrium entropy as a primitive concept. In this framework, Clausius inequality of open systems can be derived by use of the defining inequalities which establish the non-equilibrium quantities contact temperature and non-equilibrium molar entropy which allow to describe the interaction between the Schottky system and its controlling equilibrium environment.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

The paper is a kind of a small guide book through the textures and structures of river deposits in valleys. It presents principles of the flument systems with morphological river terraces and fluments (terrace bodies), different stages of the morphological terraces, structure of the flument, texture of terrace flights, terrace stacks and terrace rows. Special topics deal with flument overlaps and insight into the valley ground.

Information is physically measurable as a selection from a set of possibilities, the domain of information. This defines the term "information". The domain of the information must be known together reproducibly beforehand. As a practical consequence, digital information exchange can be made globally efficient, interoperable and searchable to a large extent by online definition of application-optimized domains of information. There are even more far-reaching consequences for physics. The purpose of this article is to present prerequisites and possibilities for a physical approach that is consistent with the precise definition of information. This concerns not only the discretization of the sets of possible experimental results, but also the order of their definition along time. The access to or comparison with the domain of information is the more frequent, the earlier it was defined. The geometrical appearance of our space is apparently a delayed statistical consequence of a very frequent connection with the common primary domain of information.

As a first step a unification of the gravitational with the electromagnetic interaction within a classical framework is proposed. It is based on a V₅-geometry, with x₅ = q/m. The sole source term is mechanical stress energy, positioned along x₅. The trajectories of test-bodies are placed in V₄ (x₅ = const)-slices. The resulting field equation couples a geometric G-tensor to mechanical stress energy, its momentum with respect to V₅ and the change of this momentum with proper time τ. The following step proceeds to the quantization of space-time to enable the formalization of elementary particles und strong interaction. This is complimented by the inclusion of spin and the weak force, leading finally to a grand total equation, the stationary version of which corresponds to Schroedinger´s equation, the instationary version to the Einstein equation of General Relativity.

Light can interfere like a wave in a multi-path experiment, but it also has particle properties when interacting with matter. In a closer look, the interference pattern is created by many individual detections ("clicks"), which do not all occur simultaneously. An established assumption is therefore that a single light particle is capable of interfering with itself by superimposing all possibilities to get from the source to the detector. This is in stark contrast to our experience with macroscopic objects, which always "decide" in favour of only one of the alternative paths.In 2010, Jin et al. (Ref. 15) described an event-based model which allowed the authors to show that an interference pattern consisting of clicks can arise in a multi-path experiment even if photons, like macroscopic objects, only follow one path. To do this, photons must be able to transmit the information about their travelling duration to the detector and the detector must have a basic memory. A threshold function uses the message of several light quanta to decide whether a single detection is initiated, which is not the evidence for a single photon. In this "proof of principle", the authors do not claim that the detector function is a realistic one.In the present paper, this detector is replaced by a material consisting of ionizable molecules whose interaction with light takes place according to a modified version of Einstein's radiation laws. Based on this, a photon pair interaction mediated by matter takes place, which in a multi-path experiment generates an interference pattern of clicks at the detector, even if an arbitrary amount of time elapses between the individual detections. In the present model an interference pattern with minima that have less than half the intensity of the maxima is the result of a peculiar behaviour of the detector: In this case, the entirety of its electrons must be described as a unit (a “field”) with many equidistant energy levels. The results of a simulation are presented which enable the model to be tested in experiments.

Dynamic simulation of district heating and cooling networks has an increased importance in the transition towards renewable energy sources and lower temperature district heating grids, as both temporal and spatial behavior need to be considered. Even though a lot and research and development has been performed in the field, there are several pitfalls and challenges towards dynamic district heating and cooling simulation for everyday use. This article presents the experiences from working with district heating and cooling projects, along with relevant research, corresponding research gaps and proposed research directions.

A novel technique suitable for propulsion of small unmanned aerial vehicles (UAV) is discussed in this paper. This approach utilizes the rotational energy of airborne gyro rotors and converts it into translational propulsion for the vehicle. The energy conversion is achieved by generating precisely directed centrifugal force pulses through short-duration rotor unbalances. The accurate control of the timing and magnitude of these unbalances is crucial for successful propulsion generation. Our first-order theory of controlled unbalance propulsion (CUP) predicts the potential for achieving high translational accelerations and vehicle velocities up to orbital levels. Power saving levitation of UAVs can be attained. In this paper, we provide traceable evidence that pulsed centrifugal propulsion is based on well-established laws of physics and can be realized using state-of-the-art technologies.

Effective sports training should be attuned to the athlete's specific conditionings and characteristics. In motor learning research, two often neglected factors that influence this resonance are the learner's athletic background and the structural diversity of exercises (e.g., relative similarity). This study examines the effects of three learning approaches (i.e., contextual interference (CI), differential learning (DL), and free-play control condition (CO)) on the parallel learning of Handball (HB), Volleyball (VB), and Basketball (BB) skills, considering participants' prior sport backgrounds. Forty-five males (15 HB, 15 VB, and 15 BB players) with a mean age of 22±1.4 years and at least 6 years of experience in the mastered discipline voluntarily participated in this study. A pre-post-retention test design including a 6-week-intervention program was employed. In terms of short-term (pre-post) gain, only the DL- group significantly improved their performance in both non-mastered disciplines (p=0.03 for the BB free-throw and p=0.05 for the HB shooting tests), with a trend (ES=0.53) towards an improvement in the performance of the mastered VB underarm-pass skill. In terms of relatively permanent gains, the CI group significantly improved their performances from pre- to retention-test only in the non-mastered BB free-throw skill (p=0.018). In contrast, the DL group significantly improved their performance at retention compared to the pre-test in both non-mastered BB (p=0.004) and HB (p=0.003) skills, with a trend (ES=0.4) towards improvement in the mastered VB test. In both short, and relatively permanent terms, higher composite score gains were observed in DL compared to CI (p=0.001 and 0.002) and CO (p=0.001 and <0.0001). In conclusion, the present findings provide additional support for the potential advantages of the DL model over those of CI. These findings can serve as the basis for tailored training and intervention strategies and provide a new perspective for addressing various issues related to individual and situational learning.

Internal and mesoscopic variables differ from each other fundamentally: both are state space variables, but mesoscopic variables are additional equipped with a distribution function introducing a statistical item into consideration which is missing in connection with internal variables. Thus, the alignment tensor of liquid crystal theory can be introduced as an internal variable or as one generated by a mesoscopic background using the microscopic director as mesoscopic variable. Because the mesoscopic variable is part of the state space, the corresponding balance equations change into mesoscopic balances, and additionally an evolution equation of the mesoscopic distribution function appears. The flexibility of the mesoscopic concept is not only demonstrated for liquid crystals, but is also discussed for dipolar media and flexible fibers.

We report on an exploratory study conducted at a graduate school in Sweden with a humanoid robot, Baxter. First, we describe a list of potentially useful capabilities for a robot teaching assistant derived from brainstorming and interviews with faculty members, teachers, and students. These selected capabilities consist of reading, greeting, alerting, remote operation, clarification, and motion. Second, we present feedback on how the robot's capabilities, demonstrated in part with the Wizard of Oz approach, were perceived, and iteratively adapted over the course of several lectures, using the \EP tool. Third, we discuss observations and findings regarding the capabilities and the development process. Our findings suggest that using a social robot as a teaching assistant is promising using the chosen capabilities. We find that personalizing the capabilities and the role of embodiment are important topics to be considered in future work.

Opioid analgesics are effective pain therapeutics but cause various adverse effects and addiction. For safer pain therapy, biased opioid agonists selectively target distinct m opioid receptor (MOR) conformations, while the potential of biased opioid antagonists has been neglected. Agonists convert a dormant receptor form (MOR-m) to a ligand-free active form (MOR-m*), which mediates MOR signaling. Moreover, MOR-m converts spontaneously to MOR-m* (basal signaling). Persistent upregulation of MOR-m* has been invoked as a hallmark of opioid dependence. Contrasting interactions with both MOR-m and MOR-m* can account for distinct pharmacological characteristics of inverse agonists (naltrexone), neutral antagonists (6b-naltrexol), and mixed opioid agonist-antagonists (buprenorphine). Upon binding to MOR-m*, naltrexone but not 6b-naltrexol suppresses MOR-m*signaling. Naltrexone blocks opioid analgesia non-competitively at MOR-m*with high potency, whereas 6BN must compete with agonists at MOR-m, accounting for ~100-fold lower in vivo potency. Buprenorphine’s bell-shaped dose-response curve may also result from opposing effects on MOR-m and MOR-m*. In contrast, we find that 6b-naltrexol potently prevents dependence, below doses affecting analgesia or causing withdrawal, possibly binding to MOR conformations relevant to opioid dependence. We propose that 6b-naltrexol is a biased opioid antagonist modulating opioid dependence at low doses, opening novel avenues for opioid pain therapy and use management.

We discuss slip bonds, catch bonds and the tug-of-war mechanism using mathematical arguments. We propose simple 2-dimensional surface models to demonstrate how the potential energy surface of a molecule under an external force behaves. Examples are selectines. Catch bonds in particular are explained in more detail. We demonstrate that Newton trajectories are a powerful tool to describe these phenomena. Newton trajectories form the theoretical background of Mechanochemistry.

In the present work, three different atmospheric plasma sprayed (APS) alumina coatings were fabricated using three fused and crushed alumina powders of different particle size fine, medium and coarse. The influence of the particle size on thermal properties and micro-structural features of the produced coating were investigated by thermal insulation test and detailed image analysis technique, respectively. The analyzed micro-structural features include the total porosity, pore size (fine, medium, and large) and cracks. All types of cracks were considered in calculations as voids and were evaluated according to their sizes as pores. All spray parameters except the particle size were fixed throughout the spraying process. The results revealed that the fine starting powder has produced the densest coating with the lowest total porosity and that the total porosity increases with an increasing particle size. This was expected as powders of smaller particle size will reach a higher in-flight temperature and velocity than powders of bigger particle sizes as long as the same spray parameters are applied. However, a detailed image analysis investigation on the three produced coatings showed that the fraction of fine pores and cracks versus the total porosity is substantially higher in coatings produced by using fine starting powders than those produced using medium and coarse powders. In this work, a connection between the thermal insulation and the porosity fraction, which includes fine pores and cracks, was revealed.

Self-assembling films typically used for colloidal lithography have been applied to pine wood substrates to change the surface wettability. Therefore, monodisperse polystyrene (PS) spheres have been deposited onto a rough pine wood substrate via dip coating. The resulting PS sphere film resembled a polycrystalline FCC-like structure with typical domain sizes of 5 – 15 single spheres. This self-assembled coating was further functionalized via an O2 plasma. This plasma treatment strongly influenced the particle sizes in the outermost layer, and hydroxyl as well as carbonyl groups were introduced to the PS spheres’ surfaces, thus generating a superhydrophilic behaviour.

This review summarizes experimental and theoretical studies of transition metal complexes with two types of novel metal-carbon bonds. One type features complexes with carbones CL2 as ligands, where the carbon(0) atom has two electron lone pairs which engage in double (σ and π) donation to the metal atom [M] CL2. The second part of this review reports complexes which have a neutral carbon atom C as ligand. Carbido complexes with naked carbon atoms may be considered as endpoint of the series [M]-CR3 → [M]-CR2 → [M]-CR → [M]-C.

Light can interfere like a wave in a multi-path experiment, but it also has particle properties when interacting with matter. In a closer look, the interference pattern is created by many individual detections ("clicks"), which do not all occur simultaneously. An established assumption is therefore that a single light particle is capable of interfering with itself by superimposing all possibilities to get from the source to the detector. This is in stark contrast to our experience with macroscopic objects, which always "decide" in favour of only one of the alternative paths.In 2010, Jin et al. (Ref. 15) described an event-based model which allowed the authors to show that an interference pattern consisting of clicks can arise in a multi-path experiment even if photons, like macroscopic objects, only follow one path. To do this, photons must be able to transmit the information about their travelling duration to the detector and the detector must have a basic memory. A threshold function uses the message of several light quanta to decide whether a single detection is initiated, which is not the evidence for a single photon. In this "proof of principle", the authors do not claim that the detector function is a realistic one.In the present paper, this detector is replaced by a material consisting of ionizable molecules whose interaction with light takes place according to a modified version of Einstein's radiation laws. Based on this, a photon pair interaction mediated by matter takes place, which in a multi-path experiment generates an interference pattern of clicks at the detector, even if an arbitrary amount of time elapses between the individual detections. In the present model an interference pattern with minima that have less than half the intensity of the maxima is the result of a peculiar behaviour of the detector: In this case, the entirety of its electrons must be described as a unit (a “field”) with many equidistant energy levels. The results of a simulation are presented which enable the model to be tested in experiments.

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

Cutaneous melanoma (CM) is a candidate for screening programs, since its prognosis is excellent when diagnosed in an early disease stage. Targeted screening of those at high risk for developing CM, a cost-effective alternative to population-wide screening, requires valid procedures to identify the high-risk group. Self-assessment of the number of nevi has been suggested as a component of such procedures, but its validity has not yet been established. We analyzed the level of agreement between self-assessments and expert assessments of the number of melanocytic nevi in the area between the wrist and the shoulder of both arms based on 4548 study subjects in whom mutually blinded double counting of nevi was performed. Nevus counting followed the IARC protocol. Study subjects received written instructions, photographs, a mirror, and a “nevometer” to support self-assessment of nevi larger than 2 mm. Nevus counts were categorized based on the quintiles of the distribution into five levels defining a nevus score. Cohen’s weighted kappa-coefficient was estimated to measure the level of agreement. In the total sample, agreement between self-assessments and expert-assessments was moderate (raw agreement: 50.29%, weighted κ=0.596). Self-assessed nevus counts were higher than those determined by experts (mean differ-ence: 3.33 nevi). The level of agreement was independent of sociodemographic and cutaneous factors; however, participants’ eye color had a significant impact on the level of agreement. Our findings show that even with comprehensive guidance, only a moderate level of agreement between self-assessed and expert-assessed nevus counts can be achieved. Self-assessed nevus information does not appear to be reliable enough to be used in individual risk assessment to target screening activities.

We apply hierarchical clustering (HC) of DNA k-mer counts on multiple Fastq files. The tree structures produced by HC may reflect experimental groups and thereby indicate experimental effects, but clustering of preparation groups indicates the presence of batch effects. Hence, HC of DNA k-mer counts may serve as an unspecific diagnostic device. In order to provide a simple applicable tool we implemented sequential analysis of Fastq reads with low memory usage in an R package (seqTools) available on Bioconductor. The approach is validated by analysis of Fastq file batches containing RNAseq data. Analysis of three Fastq batches downloaded from ArrayExpress indicated experimental effects. Analysis of RNAseq data from two cell types (dermal fibroblasts and Jurkat cells) sequenced in our facility indicate presence of batch effects. The observed batch effects were also present in reads mapped to the human genome and also in reads filtered for high quality (Phred > 30). We propose, that hierarchical clustering of DNA k-mer counts provides an unspecific diagnostic tool and a quality criterion and for RNAseq experiments.

Natural products have been used for the treatment of human diseases since ancient history. Over time, due to the lack of precise tools and techniques for the separation, purification, and structural elucidation of active constituents in natural resources there has been a decline in financial support and efforts in characterization of natural products. Advances in the design of chemical compounds and the understanding of their functions is of pharmacological importance for the biomedical field. However, natural products regained attention as sources of novel drug candidates upon recent developments and progress in technology. Natural compounds were shown to bear an inherent ability to bind to biomacromolecules and cover an unparalleled chemical space in comparison to most libraries used for high-throughput screening. Thus, natural products hold a great potential for the drug discovery of new scaffolds for therapeutic targets such as Sirtuins. Sirtuins are Class III histone deacetylases that have been linked to many diseases such as Parkinson`s disease, Alzheimer’s disease, type II diabetes, and cancer linked to aging. In this review, we examine the revitalization of interest in natural products for drug discovery and discuss natural product modulators of Sirtuins that could serve as a starting point for the development of isoform selective and highly potent drug-like compounds.

Up-conversion nanoparticles (UCNP) under near-infrared (NIR) light irradiation have been well investigated in the field of bio-imaging. However, the low up-conversion luminescence (UCL) intensity limits applications. Plasmatic modulation has been proposed as an effective tool to adjust the luminescence intensity and lifetime. In this study discrete dipole approximation (DDA) was explored concerning guiding the design of UCNP@mSiO2-Au structures with enhanced UCL intensity. The extinction effects of gold shells could be changed by adjusting the distance between the UCNPs and the Au NPs by synthesized tunable mesoporous silica (mSiO2) spacers. Enhanced UCL was obtained under 808 nm irradiation. Theoretical predictions could not be demonstrated to full extend by experimental data, indicating that better models for simulation need to better take into account inhomogeneities in particle morphologies.

Parasitic diseases continue represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. Suggestions for future drug development from African medicinal plants have also been provided.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that succinate-SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between succinate-SUCNR1 axis and placental angiogenesis. In our in-vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

During quasi-stationary tensile deformation of ultrafine-grained Cu-0.2 mass%Zr at 673 K and a deformation rate of about 10⁻⁴ s⁻¹ load changes were performed. Relative load reductions by more than about 25% to relative loads R < 0.75 initiate anelastic back flow. Subsequently the creep rate turns positive again and goes through a relative maximum. This is interpreted by a strain rate contribution ε ̇− from recovery of dislocations. Back extrapolation indicates that ε ̇− contributes about (20 ± 10)% to the quasi-stationary strain rate. The stress dependences of the recovery-strain rate ε ̇− and the rate ε ̇+ related with generation and storage of dislocations are discussed in terms of thermally activated processes characterized by different kinetics.

Towards smart batteries for electric vehicles (EVs) smart algorithms to control battery packs, mainly reconfigurable batteries, have to be developed. This work proposes a reinforcement learning (RL) algorithm to balance the State of Charge (SoC) of reconfigurable batteries based on the topologies half-bridge and battery modular multilevel management (BM3). As RL algorithm, Amortized Q-learning (AQL) is implemented, which allows enourmous numbers of possible configurations of the reconfigurable battery to be controlled, as well as the combination of classical controlling approach and machine learning methods. This enables safety mechanisms in control. As a neural network of the AQL a Feedforward Neuronal Network (FNN) is implemented consisting of three hidden layers. The experimental evaluation using a 12-cell hybrid cascaded multilevel converter illustrates the applicability of the method to balance the SoC and maintain the balanced state during discharge. The evaluation shows a 20.3% slower balancing compared to the classical. Nevertheless, AQL shows great potential to be applied for multiobjective optimizations as an applicable RL algorithm for control in power electronics.

Objective: The aim of this study was to evaluate the clinical outcome of patients suffering from chronic limb threatening ischemia (CLTI) and tissue loss treated with primary isolated femoral bifurcation endarterectomy (FBE) or with FBE combined with bypass surgery. Methods: This retrospective study was performed in a tertiary university based care center. Between January 2008 and December 2019 a prospectively collected database of patients suffering from CLTI and tissue loss and undergoing either primary FBE (group A) or FBE in combination with bypass surgery (group B) was analysed. Study endpoints were ulcer healing, primary and secondary patency rate, limb salvage and survival. Results: In total, FBE was performed in 73 and FBE with bypass in 60 patients. Between both groups there were no significant differences regarding demographic data or the Global Limb Anatomic Staging System (GLASS) grade III and IV of femoropopliteal lesions. After 3 years, ulcer healing could be achieved in 72% of FBE and in 75% of FBE with bypass patients. The primary patency rate was 95% and 91% for FBE and 83% and 80% for FBE with bypass after one and three years, respectively. The 3-year limb salvage rate was 78% for FBE and 84% for FBE with bypass. The secondary patency rate after one and three years was 99% and 97% for FBE and 93% and 88% for FBE with bypass. Conclusion: FBE and FBE with bypass are equally effective for ulcer healing in cases of combined CFA and superficial femoral artery lesions. There was no significant difference between both groups regarding primary and secondary patency

We transformed the existing learning program Language Shower, which is used in some Norwegian day-care centers in the Grorud district of Oslo municipality, into a digital solution using an app for smartphone or tablet with the option for further enhancement of presentation by a NAO robot. The solution was tested in several iterations and multiple day-care centers over several weeks. Measurements of the children’s progress across learning sessions indicate a positive impact of the program using a robot as compared to the program without robot. In-situ observations and interviews with day care center staff confirmed the solution’s many advantages, but also revealed some important areas for improvement. In particular, the speech recognition needs to be more flexible and robust, and special measures have to be in place to handle children speaking simultaneously.

Between a vineyard and the foliage wall of an adjacent forest, 25 traps containing different Drosophila attractants were applied on three occasions in autumn after the grape harvest. The attractant liquid was Pinot Blanc grape juice to which pure Saccharomyces cerevisiae yeast had been added to initiate fermentation. The five test variants differed in only one characteristic, namely the fermentation time, which was changed in two-day steps. Nine species of the genus Drosophila were captured, but only two were abundant enough to allow statistical analysis of variant differences in capture frequencies. Both species, D. suzukii and D. simulans, can affect the quality of the berries and ultimately the wine even before the harvest and are therefore considered pests. The studies showed that fermenting grape juice is significantly more attractive to both species than unfermented grape juice and that the attractiveness of the attractant liquid is maximised for D. simulans males with a fermentation time of seven to eight days.Parallel to this experiment, an analysis of the aroma spectrum of the fermenting grape juice was carried out with a temporal resolution of one day for the first twenty days. This made it possible to identify the aroma substances that had the highest concentrations in the time frame in which the attractant was particularly attractive and whose attractant effect should therefore be investigated further.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

More than twenty-five years ago the Global Solar UV index (UVI) has been introduced as a simple means of visualizing the intensity of ultraviolet radiation and to alert people to the need for sun protection. In our survey among directors of 436 kindergartens in southern Germany we investigated the level of awareness and knowledge about the UVI as well as the practical consequences for sun protection in kindergartens. Less than half of the directors (n=208, 47.7%) had ever heard of the UVI, and only a small minority of them (n=34, 8.7%) used the daily UVI information to adapt sun protective measures in their kindergartens. Detailed knowledge about the UVI was a rarity among the respondents. The proportion of respondents with self-perceived detailed UVI knowledge was five times higher than actual knowledge assessed by an in-depth structured interview using open-ended questions about the UVI (14.2% vs. 2.8%). No clear relationship of UVI awareness, knowledge, and use to directors' age and gender was found. The UVI-related variables also showed no association with directors' knowledge of risk factors for skin cancer and their attitudes towards tanned skin. Overall, the results paint a sobering picture regarding the penetration of the UVI into sun protection policies of German kindergartens. Future public health campaigns should target increasing awareness and understanding of the UVI as well as its importance for sun protection of children.

In this paper, we present a comprehensive 4D study of the early stage of plastic deformation in a polycrystalline binary AlLi alloy. The entire microstructure is mapped with X-ray diffraction contrast tomography and a set of bulk grains is further studied via X-ray topotomography during mechanical loading. The observed contrast is analyzed with respect to the slip system activation and the evolution of the orientation spread is measured as a function of applied strain. The experimental observations are augmented by the mechanical response predicted by crystal plasticity finite element simulations to analyze the onset of plasticity in details. Simulation results show a general agreement of the individual slip system activation during loading and that comparison with experiments at the length scale of the grains may be used to fine tune the constitutive model parameters.

Pearl millet is an important food crop in the arid and semi-arid tropical regions of Africa and Asia. These regions are home to millions of poor smallholder’s households living in harsh agro ecology and reported higher prevalence of malnutrition. Such poor households have few options in terms of food crops, besides the limited markets. Indeed, pearl millet is one of the food crops they continue to grow for their food and nutritional security. Pearl millet is important sources of dietary carbohydrates, energy, protein, and important minerals such as calcium, iron and zinc. Considering inherent high nutritional values and climate resilient nature (drought and heat), demand for pearl millet as food, beside valued for its Stover as a source of livestock fodder, is projected to grow strongly in Asia (India) and Africa (West and Central Africa). Iron (cause anemia) and zinc (cause stunting) deficiencies are widespread and serious public health problems worldwide, including India and Africa. Biofortification is a cost-effective and sustainable agricultural strategy to address this problem. Research on pearl millet has shown that large genetic variability (30-140 mg/kg Fe and 20-90 mg/kg Zn) available in this crop can be effectively utilized to develop high-yielding cultivars with high iron and zinc densities. Both Open –pollinated varieties (Dhanshakti and Chakti) and hybrids (ICMH 1202, ICMH 1203 and ICMH 1301) of pearl millet with high grain yield (>3.5 tons/ha in hybrids) and high levels of iron (70-75 mg/kg) and zinc (35-40 mg/kg) densities have been developed and released. Currently, India growing >70,000 ha of biofortified pearl millet, besides more pipeline hybrids and varieties are under various stage of testing at the national (India) and international (west Africa) trials for possible release. Genomic tools will be an integral part of breeding program particularly for nutritional traits to use diagnostic markers and genomic selection. Clinical studies showed that 200g grains from biofortified cultivar would provide bioavailable Fe to meet full recommended daily allowance (RDA) in children, adult men and 80% of the RDA in women. Till today, no markets to promote biofortified cultivars/grains/products as no incentive price and such products aims to address food and nutritional security challenges simultaneously. The demand is likely to increase only after investment and integration into modern public distribution system, nutritional intervention schemes, private seed and food companies with strong mainstreaming nutritional policies. In the non-traditional regions, this will contribute to livestock and poultry feed industry as spill-over benefits to improve nutrition.

The need for multi-gene analysis in evolutionary and taxonomic studies is generally accepted. However, sequencing of multiple genes is not always possible. For various reasons, short mito-chondrial DNA barcodes are the only source of molecular information for some species in many genera, although multilocus data are available for other species of the same genera. In particular, such a situation exists in the species-rich butterfly subgenus Polyommatus (Agrodiaetus). Here, we analysed partitioning of this subgenus into species groups by using three data sets. The first data set was represented by short mitochondrial DNA barcodes for all analysed samples. The second and third data sets were represented by combination of short mitochondrial DNA barcodes for a part of the taxa with longer mitochondrial sequences COI+tRNA-Leu+COII (data set 2) and with longer mitochondrial COI+tRNA-Leu+COII and nuclear 5.8S rDNA+ITS2+28S rDNA sequences (data set 3) for the remaining species. We show that DNA barcoding approach (data set 1) failed to reveal the taxonomic structure resulting in numerous polytomies in the phylogenetic tree ob-tained. Combined analysis of the mitochondrial and nuclear sequences (data sets 2 and 3) re-vealed the species groups and position within these species groups even for the taxa for which only short DNA barcodes were available.

The strength of laser joined metal and plastic hybrids is based purely on adhesion. Unpolar plastics like polypropylene depend solely on the mechanical adhesion while polar plastics like polyamide 6.6 develop covalent bonds with the metal. In this research the influence of different surface metallizations on the lap shear strength of laser joined hybrids was investigated. Sandblasted AISI 304 was used as base metal and reference. Aluminum and titanium coatings were deposited by the means of Arc-PVD. Polypropylene and polyamide 6.6 were utilized as polar und unpolar plastics. The lap shear strength of all hybrids with polyamide 6.6 was higher than the polypropylene samples. For all investigated variations of the laser power, scanning speed and the cohesive and adhesive failure modes, the samples joined with the sandblasted AISI 304 showed the highest lap shear strength. The reduction in lap shear strength for the coated samples was due to the increased difference in thermal conductivity between the plastics and the coating materials. This lead to increased warping and residual stresses. It can be concluded that the thermal properties of the metallization in laser joined metal and plastic hybrids has a high impact on the lap shear strength.

Appropriate techniques for promoting reading fluency are difficult to implement in the classroom. There is little time to provide students with individualized feedback on reading aloud or to moti-vate them to do so. In this context, VR can be beneficial for learning, to provide individualized feedback and for increasing learners' engagement. Studies analyzing established methods of lan-guage learning in school in VR seem to be lacking so far. Therefore, this study project was the first to analyze the acceptance of students towards the implementation of a concept of reading fluency training with students at a secondary school in VR. The study method was developed based on the Technology Acceptance Model. The VR environment developed is web-based and provides indi-vidual and collaborative opportunities for training reading fluency, giving, and receiving feed-back, and deepening content understanding of the reading texts. To analyze the acceptance of the VR environment, 5 guided interviews were conducted. The results show that despite technical challenges with the VR environment, students accepted and appreciated the reading fluency training in VR. The integration of established concepts of reading fluency training in foreign lan-guage classrooms has great potential as additional added value can be created to address the challenges of face-to-face instruction.

Objective: CAD/CAM generated ceramic implant abutments have recently attracted interest due to their superior customization possibilities and aesthetic advantages. Despite their widespread clinical use, little information is currently available on their surface topography, however. The transmucosal portion of the abutment shoulder is of particular interest, as it ideally supports soft tissue but minimizes mechanical plaque retention. The aim of this in vitro study was to topographically characterize the trans- and subgingival roughness of CAD/CAM zirconia abutments from different manufacturers and compare them with zirconia stock abutments. Material and Method: The surface topography of eight CAD/CAM zirconia implant abutments (tests) and two prefabricated zirconia stock abutments (controls) was determined using focus variation microscopy. Two points on the abutment shoulder were subjected to profilometric examination. 2D and 3D parameters of roughness were obtained and compared. Results: The surface roughness of all the test abutments exceeded the recommended threshold of Ra = 0.2 µm and therefore exhibited an increased risk of mechanical plaque retention. Obvious differences in surface structure were apparent, allowing conclusions to be drawn about the manufacturing method and subsequent reworking processes. Conclusion: Manually reworking the trans- and submucosal area of the investigated CAD/CAM zirconia abutments appears necessary to fulfil the conditions for optimal surface topography. The Sa value as arithmetic mean, taking the maximum height (Sz value) and surface excess (Sdr) into account, is an essential parameter for assessing the surface topography of implant abutments.

A paper impregnated with silver nanoparticles (AgNPs) has been prepared. For the preparation of the substrates, aqueous suspensions of pulp fines, a side product from the paper production, have been mixed with Ag nanoparticles (AgNP) suspensions. The nanoparticle synthesis thereof was carried out via laser ablation of pure Ag in water. After the sheet formation process, the leaching of the AgNPs was determined to be low while the sheets exhibited antimicrobial activity towards E. Coli.

This paper investigates if the polar groups induced by a plasma treatment can increase the lap shear strength of laser joined metal and plastic hybrids. Optimal laser joining parameters for cold-rolled AISI304 – Polyamide 6.6 and sandblasted AISI304 - Polypropylene hybrids are developed. The OWRK-method was utilized to identify the change in surface free energy of a low-pressure plasma treatment. Plasma treated samples were joined and tested. The fractured surfaces were investigated via light microscopy and SEM. The arithmetic means of the plasma treated hybrids lap shear strength with polyamide 6.6 varied slightly but all measured values were within the range of the untreated samples. The lap shear strengths of the polypropylene hybrids were significantly reduced. This was attributed to an overaging and the development of low molecular weight oxidized materials which lead to a weak boundary layer. No correlation between surface free energy and the lap shear strength could be found.

The formation of hydrogen sulfide (H₂S) in petroleum reservoirs by anaerobic microbial activity is called biogenic souring of reservoirs and is a risk in the oil and gas industry as the compound is extremely toxic, flammable and corrosive. In this paper, we present a workflow and the tools to assess biogenic souring from a pragmatic engineering perspective. The retention of H₂S in the reservoir due to the reactions with iron-bearing rock minerals (e.g. siderite) is shown in a theoretical approach here and supported with literature data. Cases are given for two fields under secondary (waterflooding) and tertiary flooding with microbial enhanced oil recovery (MEOR). The use of the Monte Carlo method as a numerical modelling tool to incorporate uncertainties in the measured physical/chemical/ biochemical data is demonstrated as well. A list of studies conducted with different chemicals alone or in combination with various biocides to mitigate biogenic souring provides an overview of potential inhibitors as well as possible applications. Furthermore, the results of static and dynamic inhibition tests using molybdate are presented in more detail due to its promising mitigation ability. Finally, a three-step workflow for the risk assessment of biogenic souring and its possible mitigation is presented and discussed.

Two histamine receptor subtypes (HR), namely H1R and H4R, as key components, are involved in the transmission of histamine-induced itch. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. Aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo and in vitro via Ca2+ imaging of murine sensory dorsal root ganglia (DRG) neurons. The TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch and reduced Ca2+ influx into the neurons. The TRPA1 inhibitor reduced H4R-induced itch and both H1R- and H4R-induced Ca2+ influx. In conclusion, these results indicate that both channels, TRPV1 and TRPA1 are involved in the transmission of histamine-induced pruritus.

In this work, an evanescent Bragg grating sensor inscribed in a few-mode planar polymer waveguide was integrated in microchannel structures and characterized with various chemical applications. The planar waveguide and the microchannels consisted of epoxide-based polymers. The Bragg grating structure was post-processed using point-by-point direct inscription technology. By monitoring the central wavelength shift of the reflected Bragg signal, the sensor showed a temperature sensitivity of -47.75 pm/K. Moreover, the functionality of the evanescent field-based measurements is demonstrated with two application examples: refractive index sensing of different aqueous solutions and gas-phase hydrogen concentration detection. For the latter application, the sensor was additionally coated with a functional layer based on palladium nanoparticles. During the refractive index sensing measurement, the sensor achieved a sensitivity of 6.5 nm/RIU from air to 99.9% pure isopropyl alcohol. For the gas-phase hydrogen detection, the coated sensor achieved a reproducible concentration detection up to 4 vol% hydrogen. According to the reported experimental results, the integrated Bragg grating-based waveguide sensor demonstrates high potential for applications based on lab-on-a-chip concept.

The hydrogen evolution reaction (HER) has garnered attention to access sustainable energy generation with a pollutant-free combustion product in the form of H2 gas. Despite the utility of this pathway in the context of growing climate concerns, stable HER electrocatalysts which avoid the use of rare-earth platinum while retaining high catalytic performance and efficiency remains a challenge. In this work, we present the application of a binuclear nickel (II/III) Schiff base complex [Ni]2[L]2 2 for HER electrocatalysis. The design of the electrocatalyst provides optimal HER activity as the presence of electronegative heteroatoms in proximity to the metal centers augments proton affinity. As a result, the catalyst displays excellent HER activity with 100% faradaic efficiency (FE) at an onset potential of 0.4 V vs. reverse hydrogen electrode (RHE), sustained catalytic activity during prolonged electrolysis for greater than 17 hours, and provided a turn over number (TON) of 0.0006 s-1.

The influence of the grain structure on the tensile deformation strength is studied for precipitation-strengthened Cu-0.2%Zr at 673 K. Subgrains and grains are formed by ECAP and annealing. The fraction of high-angle boundaries increases with prestrain. Subgrains and grains coarsen during deformation. This leads to softening in the quasi-stationary state. The initial quasi-stationary state of severely predeformed, ultrafine-grained material exhibits relatively high rate-sensitivity at relatively high stresses. This is interpreted as result of the stress dependences of the quasi-stationary subgrain size and the volume fraction of subgrain-free grains.

LC–NMR combines the advantage of the outstanding separation power of liquid chromatography (LC) and the superior structural elucidating capability of nuclear magnetic resonance (NMR). NMR has proved that it is a standout detector for LC by providing maximum structural information about plant originated extracts particularly in its isolating ability of isomeric (same molecular formula) and/or isobaric (same molecular weight) compounds as compared to other detectors. The present review provides an overview of the LC–NMR developmental trends and its application in natural products analysis. The different LC–NMR operational modes are described, as well as how technical improvements assist in establishing this powerful technique as an important analytical tool in the analysis of complex plant-derived compounds. On-flow, stop-flow and loop-storage modes, as well as the new offline mode LC–SPE–NMR and capLC-NMR configurations that avoid the ingestion of expensive deuterated solvents throughout the experiment are mentioned. Utilization of cryogenic probe and microprobe technologies which are the other important promising approaches for guaranteeing the sensitivity issues are also described. Concluding remarks and future outlooks are also discussed.

The Norwegian Museum of Science and Technology have developed a learning concept for school classes in science centres named ‘learning trails’. In this concept, groups of students perform a series of thematically related experiments with installations in the science centre. The learning trails are designed to support the generic learning outcomes for science centre visits. We argue for using the previously developed Engagement Profile in an indicator to determine both media forms and generic learning outcomes for such learning concepts. Further, we implemented the learning trails in two modes: one mode used paper-based content to guide the students, while the other mode supported the use of tablet PCs where engaging content is triggered when the students approach the location of an experiment in the learning trail. We studied the engagement factors of the learning trails and observed how school classes use these. In a study with 113 students from lower secondary school, they answered short questionnaires that were integrated into the implementation of the learning trails. While the concept of the learning trails was evaluated positively, we could not find significant differences in how engaging the two implemented modes were.

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world's population with vaccines, demonstrating protection from infection and transmission, being available in large quantities and at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g., as a consequence of allograft transplantation, cannot be immunized actively nor produce sufficient immune responses to prevent SARS-CoV-2 infections. These subjects desperately need other strategies, such as sophisticated protection measures and active immunization. Hypertonic salt solutions attack vulnerable core areas of viruses, i.e., salt denatures surface proteins and thus prohibits virus penetration of somatic cells. It has to be ensured that somatic proteins are not affected by denaturation regarding this unspecific virus protection. Impregnating filtering facepieces with hypertonic salt solutions is a straightforward way to inactivate viruses and other potential pathogens. As a result of the contact of salt crystals on the filtering facepiece, these pathogens become denatured and inactivated almost quantitatively. Such a strategy could be easily applied to fight against the COVID-19 pandemic and other ones that may occur in the future. Another possible tool to fight the COVID-19 pandemic is passive immunization with antibodies against SARS-CoV-2, preferably from human origin. Such antibodies can be harvested from patients´ human sera, which have successfully survived their SARS-CoV-2 infection. The disadvantage of a rapid decrease of the immunoglobulin titer after infection ends can be overcome by immortalizing antibody-producing B-cells via fusion with, e.g., mouse myeloma cells. The resulting monoclonal antibodies are then of human origin and available in, at least theoretically, unlimited amounts. Finally, dry blood spots are a valuable tool for surveilling the population´s immunity.

The research methods were used to investigate the following questions: Does a mobility training intervention change tissue stiffness, joint range of motion, and compensate for possible imbalances? Do the interventions influence the pressure pain threshold and the overall well-being?

Variable during practice is widely accepted to be advantageous for motor learning and therefor a valuable strategy to effectively reduce high-risk landing mechanics and prevent primary anterior cruciate ligament (ACL) injury. Few attempts have examined the specific effects of variable train-ing in athletes who have undergone ACL reconstruction. Thereby it is still unclear to what extent the variations in different sensor areas lead to different effects. Accordingly, we compared the effects of versatile movement variations (DL) with variations of movements with emphasis on disrupting visual information (VMT) in athletes who had undergone ACL reconstruction. For-ty-five interceptive sports athletes after ACL reconstruction were randomly allocated to a DL group (n= 15), VT group (n= 15) or control group (n= 15). The primary outcome was functional performance (Triple Hop Test). The secondary outcomes included dynamic balance (Star Excur-sion Balance Test (SEBT)), biomechanics during single-leg drop-landing task hip flexion (HF), knee flexion (KF), ankle dorsiflexion (AD), knee valgus (KV), and vertical ground reaction force (VGRF), and kinesiophobia (Tampa Scale of Kinesiophobia (TSK)) assessed before and after the 8-weeks of interventions. Data were analyzed be means of 3×2 repeated measures ANOVA fol-lowed by post hoc comparison (Bonferroni) at the significance level of p≤0.05. Significant group × time interaction effects, main effect of time and main effect of group were found for triple hop test, all eight directions of SEBT, HF, KF, AD, KV, VGRF and TSK. There was no significant main ef-fect of group in HF and triple hop test. Also, significant differences in triple hop test, seven direc-tions of SEBT, HF, KF, KV, VGRF and TSK were found between control group with the DL and VMT groups. Between group differences in AD and medial direction of SEBT were not signifi-cant. Also, there was no significant differences between VMT and control groups in triple hop test and HF variables. Both motor learning (DL and VMT) programs improved outcomes in patients after ACL reconstruction. Findings suggest that DL and VMT training programs lead to compa-rable improvements in rehabilitation.

The demand for explainable and transparent models increases with the continued success of reinforcement learning. In this article, we explore the potential of generating shallow decision trees (DT) as simple and transparent surrogate models for opaque deep reinforcement learning (DRL) agents. We investigate three algorithms for generating training data for axis-parallel and oblique DTs with the help of DRL agents ("oracles") and evaluate these methods on classic control problems from OpenAI Gym. The results show that one of our newly developed algorithms, the iterative training, outperforms traditional sampling algorithms, resulting in well-performing DTs that often even surpass the oracle from which they were trained. Even higher dimensional problems can be solved with surprisingly shallow DTs. We discuss the advantages and disadvantages of different sampling methods and insights into the decision-making process made possible by the transparent nature of DTs. Our work contributes to the development of not only powerful but also explainable RL agents and highlights the potential of DTs as a simple and effective alternative to complex DRL models.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low dose. Secondary aims were to identify associated behavioural side effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, a single intravenous bolus of 1 mg/kg racemic ketamine was administered over 2 minutes. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 minute, followed by an infusion at 0.01 mg/kg/min for 1 hour. Blood samples were collected from the left cephalic vein for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. However, levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady state racemic ketamine plasma concentration of 150 ng/mL was 1.7 mg/kg/h. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

Objectives and Background: Gestational diabetes (GDM) is a common pregnancy complication, defined as a glucose intolerance diagnosis during pregnancy. GDM is strongly associated with adverse fetal and maternal outcomes. In Germany, to screen and diagnose GDM we use a 1-hour 50g oGCT (oral glucose challenge test) followed by a 2-hour 75g oGTT if the first was pathological. This analysis examines the correlation of 75g oGTT glucose levels and fetomaternal outcome. Methods: Data of 1664 patients from a gestational diabetes consultation clinic at the Charité University hospital in Berlin, Germany, were analyzed retrospectively from 2015 until 2022. The 75g oGTT blood glucose levels were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated post-load hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1-hour and 2-hour values after glucose application. These subtypes were compared regarding baseline characteristics as well as fetal and maternal outcome. Results: GDM-IFH and GDM-CH women displayed higher preconceptional BMI and required insulin therapy more frequently (p<0,001). The GDM-IFH group was at higher risk of having a primary cesarean section (p=0,047), while GDM-IPH women were significantly more likely to have an emergent cesarean section (p=0,013). The offspring of GDM-IFH and GDM-CH women were born with a significantly higher mean birthweight (p<0,001) and birth weight percentiles (p<0,001) and were at increased risk of being large for gestational age (LGA) (p=0,004). Women from the GDM-IPH group delivered significantly more neonates who were small for gestational age (p=0,027) or with low fetal weight <30th percentile (p=0,003). Conclusion: This analysis shows a strong association between glucose response pattern in the 75g oGTT and adverse perinatal fetomaternal outcome. The differences among the subgroups, specifically concerning insulin therapy, mode of delivery and fetal growth, suggest an individualized approach in prenatal care after a GDM diagnosis.

Museums and Science Centres are informal education environments that intend to engage the visitors with their exhibits. We present an efficient design process that allows an improved working relationship between museum practitioners, exhibition designers, and visitors. We present the principles and a graphical representation based on the Engagement Profile from previous work. Elements of the design process are evaluated using a learning game at the science centre Engineerium. The evaluation is based on a study with over five hundred visitors to the science centre.

Plastics have become an important environmental concern due to their durability and resistance to degradation. Out of all plastic materials, polyesters such as polyethylene terephthalate (PET) are amenable to biological degradation due to the action of microbial polyester hydrolases. The hydrolysis products obtained from PET can thereby be used for the synthesis of novel PET as well as becoming a potential carbon source for microorganisms. In addition, microorganisms and biomass can be used for the synthesis of the constituent monomers of PET from renewable sources. The combination of both biodegradation and biosynthesis would enable a completely circular bio-PET economy beyond the conventional recycling processes. Circular strategies like this could contribute to significantly decrease the environmental impact of our dependence on this polymer. Here we review the efforts made towards turning PET into a viable feedstock for microbial transformations. We highlight current bottlenecks in the degradation of the polymer and the metabolism of the monomers and we showcase fully biological or semisynthetic processes leading to the synthesis of PET from sustainable substrates.

Whole-body electromyostimulation (WB-EMS) can be considered as a time-efficient, joint-friendly and highly customizable training technology that attracts a wide range of users. The present evidence map aimed to provide an overview of different non-athletic cohorts addressed by WB-EMS research. Based on a comprehensive systematic search according to PRISMA, eighty-six eligible longitudinal trials were identified that correspond with our eligibility criteria. In summary, WB-EMS research sufficiently covers all adult age categories in males and females. Most cohorts addressed (58%) were predominately or exclusively overweight/obese and in about 60% of them, diseases or conditions were inclusion criteria for the trials. Cohorts specifically addressed by WB-EMS trials suffer from cancer/neoplasm (n=7), obesity (n=6), diabetes mellitus (n=5), the metabolic syndrome (n=2), nervous system diseases (n=2), chronic heart failure (n=4), stroke (n=1), peripheral arterial diseases (n=2), knee arthrosis (n=1), sarcopenia (n=3), chronic unspecific low back pain (n=4), and osteopenia (n=3). Chronic kidney disease was an eligibility criterion in five WB-EMS trials. Finally, three studies included only critically ill patients, two further studies considered frailty as an inclusion criterion. Of importance, no adverse effects of the WB-EMS intervention were reported. In summary, evidence gaps of WB-EMS research were particular evident for cohorts with diseases of the nervous and cerebrovascular system.

Arf-like protein 2 (ARL2) is a ubiquitously expressed small GTPase with multiple functions. In cell culture, ARL2 participates with tubulin cofactor D (TBCD) in the neogenesis of tubulin αβ-heterodimers, the building blocks of microtubules. To evaluate this function in retina, we conditionally deleted ARL2 in mouse retina at two distinct stages, either during embryonic development (retArl2-/-) or after ciliogenesis specifically in rods (rodArl2-/-). retArl2-/- retina sections displayed distorted nuclear layers and a disrupted microtubule cytoskeleton (MTC) as early as postnatal day 6 (P6). Rod and cone outer segments (OS) did not form. By contrast, rod ARL2 knockouts were stable at postnatal day 35 and revealed normal ERG responses. Cytoplasmic dynein is reduced in retArl2-/- inner segments (IS), suggesting that dynein may be unstable in the absence of a normal MTC. We investigated microtubular stability in the absence of either ARL2 (retARL2-/-) or DYNC1H1 (retDync1h1-/-), the dynein heavy chain, and found that both the retArl2-/- and retDync1h1-/- retinas exhibited reduced microtubules and nuclear layer distortion. The results suggest that ARL2 and dynein depend on each other to generate a functional MTC during early photoreceptor development.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

Due to its time effective, joint friendly and highly customizable character whole-body-electromyostimulation (WB-EMS) is regarded as a feasible solution for a large variety of training issues particularly in the area of non-athletic application. To identify gaps in research and summarize prevalent evidence we conducted an evidence map on outcomes addressed by WB-EMS trials in middle-aged to older, non-athletic adults. Based on a comprehensive systematic search in five databases and two study registers according to PRISMA, 54 projects published in 80 articles were included. More than 90% of the studies reported outcomes related to the physical fitness or function domain. Body composition parameters were addressed by two thirds of the projects. Health-related outcomes addressed by WB-EMS included cancer/neoplasm (n=7), endocrine regulation (n=8), glucose metabolism (15), nervous system diseases (n=2), cardiovascular system diseases (n=22), non-specific chronic low back pain (n=4), osteopenia (n=5) and diseases of the renal system (n=12). Outcomes related to inflammation were addressed 18 times. Of importance, no studies reported clinically relevant adverse effects related to the WB-EMS intervention. In summary, while considerable evidence on outcomes related to fitness/function and body composition is prevalent, evidence gaps of WB-EMS research were particular evident for diseases of the nervous and cerebrovascular system.

Sirtuins are nicotinamide adenine dinucleotide (NAD⁺)-dependent class III histone deacetylases and have been linked to the pathogenesis of numerous diseases such as HIV, metabolic disorders, neurodegeneration and cancer. Docking of the virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted in the identification of two inhibitors of sirtuin 1, 2 and 3 (sirt1-3). Two bichalcones; rhuschalcone IV (8) and rhuschalcone I (9), previously isolated from the medicinal plant Rhus pyroides, were shown to be active in the in vitro assay, with rhuschalcone I showing the best activity against sirt1, having an IC₅₀ = 40.8 µM. Based on the docking experiments, suggestions for improving the biological activities of the newly identified hit compounds have been provided.

The current state-of-the-art does not provide a universal and rapid method of determining the state of health (SOH) of a battery or a supercapacitor without carefully examining the degradation of hundreds of full charge/discharge cycles. Lithium-ion batteries, sodium-ion batteries and supercapacitors of different cell chemistries were studied by impedance spectroscopy during lifetime tests. Faradaic and capacitive charge storage are distinguished by the relationships between stored electric charge and capacitance. For batteries, impedance spectroscopy is best applicable in the flat region of the voltage-charge curve. An approximately linear correlation between pseudocapacitance and Ah capacity is observed as long as overcharge and deep discharge are avoided. The correct calculation of quantities related to complex impedance and differential capacitance is outlined – which may also be useful as an introductory text and tutorial for newcomers to the field. Novel diagram types are proposed for the purpose of instant performance and failure diagnosis of batteries and supercapacitors.

Objective: This prospective study aimed to compare the efficacy of caudal block (CB) and inguinal block (IB) for providing additional analgesia during unilateral orchidopexy. Methods: Seventy-two boys aged &lt;48 months, classified as ASA I/II, were assigned into CB (n=37) and IB (n=34) groups. Outcome measures included intra- and postoperative analgesic requirements, pain scores, and administration duration. Additional intraoperative analgesia was administered for a 10% increase in heart rate, while postoperative pain was assessed using the Children's and Infants Postoperative Pain Scale (CHIPPS), with scores &gt;4 prompting supplementary analgesia. Monitoring extended for 24 hours post-surgery. Results: CB significantly reduced the need for intraoperative (p&lt;0.001) and early postoperative (p=0.008) analgesia compared to IB. Although the CB group exhibited a slightly higher but non-significant analgesic requirement on the ward. No clinically relevant side effects were observed in either group. Conclusion: Both CB and IB are effective and safe methods for providing regional analgesia during orchidopexy. CB demonstrated superior efficacy intraoperatively and in the early postoperative period, while IB may offer advantages in the later recovery phase. However, additional analgesia is often required for orchidopexy, particularly in outpatient settings.

Background/Objectives: We defined the value of a machine learning algorithm to distinguish between the EEG response to no light or any light stimulation, and between red or green light stimulation in awake volunteers with closed eyelids. This new method of EEG analysis is visionary in the understanding of visual signal processing and will facilitate anaesthetic depth research. Methods: X-gradient boosting models were used to classify the cortical response to VEP stimulation (no light vs. any light stimulation; red vs. green light stimulation). For each of the two classifications, three scenarios were tested: training and prediction in all participants (all), training and prediction in one participant (individual), training across all but one participant with prediction in the participant left out (one out). Results: Ninety-four Caucasian adults were included. The machine learning algorithm had a very high predictive value and accuracy in differentiating between no light and any light stimulation (AUCROCall: 0.96; accuracyall: 0.94; AUCROCindividual: 0.96±0.05, accuracyindividual: 0.94±0.05; AUCROConeout: 0.98±0.04; accuracyo-neout:0.96±0.04). The machine learning algorithm was highly predictive and accurate in distinguishing between green and red colour stimulation (AUCROCall: 0.97; accuracyall: 0.91; AUCROCin-dividual: 0.98±0.04, accuracyindividual: 0.96±0.04; AUCROConeout: 0.96±0.05; accuracyoneout: 0.93±0.06). The predictive value and accuracy of both classification tasks was comparable between males and females. Conclusions: Machine learning algorithms could almost continuously and reliably differentiate between the cortical EEG responses to no light or any light stimulation and between green or red colour stimulation using VEPs in awake female and male volunteers with eyes closed. Our findings may open new possibilities for using VEPs in the intraoperative setting.

The South-to-North Water Transfer Jiangsu Water Supply Area (JWSA) is a mega inter-basin water transfer area (water source) that provides water resources from JiangHuai, combines drainage and flooding management, and regulates nearby rivers and lakes. Analyzing the spatiotemporal soil moisture dynamics in the area will inform agricultural drought and flood disaster assessment and early warning studies. Therefore, we evaluated the quality of European Space Agency Climate Change Initiative Soil moisture (ESA CCI_SM) data in the South-North Water Transfer JWSA. Then, we used ensemble empirical modal decomposition, Mann-Kendall tests, and regression analysis to study the spatiotemporal variation in soil moisture for the past 29 years. The CCI _SM data showed a high correlation with local soil measurements at nine sites. We then analyzed the CCI_SM data from three pumping stations (the Gaogang, Hongze, and Liushan stations) in the South-North Water Transfer JWSA. These stations had similar periodic characteristics of soil moisture, with significant periodic fluctuations around 3.1 d. The overall soil moisture at the three typical pumping stations showed an increasing trend. We then investigated whether there were abrupt soil moisture changes at each station. The spatial distribution of soil moisture in the South-North Water Transfer JWSA was characterized by “dry north and wet south”, with higher soil moisture in winter, followed by autumn, and low soil moisture in spring and summer. Although the linear trend of soil moisture in the South-North Water Transfer JWSA varied in significance, the overall soil moisture in the JWSA has increased over the past 29 years. The areas with significantly enhanced soil moisture are mainly distributed in the Yangzhou and Huai'an areas in the southeastern part of the study area. The areas with significantly decreased soil moisture are small in size and mainly located in northern Xuzhou.

This paper presents a control algorithm for soft-switching series LC converters. The conventional voltage-to-voltage controller is split into a master and a slave controller. The master controller implements constant-current-constant-voltage (CCCV) control, required for demanding applications, i.e. lithium battery charging or laboratory power supplies. It defines the set-current for the open-loop current slave controller, which generates the PWM parameters. The power supply achieves fast large-signal responses, e.g. from 5 V to 24 V, where 95% of the target value is reached in less than 400 µs. The design is evaluated extensively in simulation and on a prototype. A consensus between simulation and measurement is achieved.

Due to the high specific surface area of titanium aluminide powders, significant and unavoidable surface oxidation takes place during processing. The resulting oxides disrupt the conventional powder metallurgical process route (pressing and sintering) by reducing green strength and sintered properties. Oxide-free particle surfaces offer the potential to significantly increase particle bond strength and enable the processing of difficult-to-press material powders. In this work, the effect of milling titanium aluminide powder in a silane-doped atmosphere on the component properties after pressing and subsequent sintering was investigated. Ball milling was used to break up the oxide layers and create bare metal surfaces on the particles. With the help of silane-doped inert gas, the oxygen partial pressure was greatly reduced during machining. It was investigated whether oxide-free surfaces could be produced and maintained by milling in silane-doped at-mospheres. Furthermore, the resulting material properties after pressing and sintering were an-alyzed using density measurements, hardness tests, EDX-measurements and micrographs. It was concluded, that ball milling in a silane-doped atmosphere produces and maintains oxide-free particle surfaces. These oxide-free surfaces and smaller particle sizes improve the component properties after pressing and sintering.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

Background. In a cannot ventilate cannot intubate situation, careful preoxygenation with high FiO₂ allowing subsequent apneic oxygenation can be life-saving. The best position for an oxygen supply line within the human airway at which oxygen insufflation is more effective than standard preoxygenation with a face mask, or comparably effective as intratracheal insufflation, is unknown. Methods. In this experimental study, we compared effectiveness of preoxygenation by placing an oxygen cannula at the nose entrance, through the nose at the soft palatine, or at the base of tongue; as control we used ambient air. We connected a fully preoxygenated test lung on one side to an oximeter with a flow rate of 200ml/min simulating oxygen consumption of a normal adult, and on the other side to the trachea of an anatomically correctly shaped airway manikin over a 20 min observation period five times for each cannula placement in random order. Results. Oxygen percentage in the test lung dropped from 100% in all groups to 53±1% in the ambient air control group, to 87±2% in the nasal cannula group, to 96±2% in the soft palatine group, while it remained at 99±1% in the base of tongue group (p=0.003 for soft palatine vs base of tongue; and p<0.001 between all other groups). Conclusions. When simulating apneic oxygenation in a preoxygenated manikin, oxygen insufflation at the base of tongue kept oxygen percentage at baseline values of 99% demonstrating a complete block for ambient air flowing into the manikin’s airway. Oxygen insufflation at the soft palatine or insufflation via nasal cannula were less effective in regard of this effect.

In the multicenter, non-randomized, exploratory C-reactive protein (CRP) Apheresis in Myocardial Infarction (CAMI-1) study, CRP apheresis after ST-Elevation Myocardial Infarction (STEMI) significantly decreased blood CRP concentrations in humans. Cardiac damage was assessed by Cardiac Magnetic Resonance (CMR1) 3-9 d after onset of STEMI symptoms and quantified by myocardial infarct size (IS; %), left ventricular ejection fraction (LVEF; %), circumferential strain (CS) and longitudinal strain (LS) Compared with the control group (n=34), cardiac damage was significantly lower in the apheresis group (n=32). These findings suggested improved wound healing due to CRP apheresis already within few days after the STEMI event. In the current supplementary data analysis of CAMI-1, we have tested by a follow-up CMR (CMR2) after an average of 88 (65-177) d whether the effect of CRP apheresis is clinically maintained. After this time period wound healing in STEMI is considered complete. Whereas patients with low CRP production and a CRP gradient cut off of &lt;0.6 mg/L/h in the hours after STEMI (9 of 32 patients in the CRP apheresis group) did not significantly benefit from CRP apheresis in CMR2, patients with high CRP production and a CRP gradient cut off of &gt;0.6 mg/L/h (23 of 32 patients in the CRP apheresis group) showed significant treatment benefit. In the latter patients, CMR2 revealed a lower IS (-5.4%; p=0.05), a better LVEF (+6.4%; p=0.03), and an improved CS (-6.1%; p=0.005). No significant improvement, however, was observed for LS (-2.9%; p=0.1). These data suggest a sustained positive effect of CRP apheresis on the heart physiology in STEMI patients with high CRP production well beyond the period of its application. The data demonstrate the sustainability of the CRP removal from plasma which is associated with less scar tissue.

Currently, SARS-CoV-2 infection which is the causative agent for COVID-19 disease is a worldwide pandemic with more than 100 million global cases and more than 2.0 million deaths (as of January, 2021). While several vaccines for prevention of COVID-19 have already been registered by the regulatory authorities, the problem is that the substitution rate of this virus is estimated to be one change per 2 weeks, thus mutations could arise that threaten the efficacy of vaccines. Unfortunately, there is no current evidence from random clinical trials to recommend any specific post-exposure treatment for patients with suspected or confirmed COVID-19 disease. Here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated harmless viruses might interact in patients infected with pathogenic virus. During SIT, the patient benefits from superinfection with an apathogenic double-stranded RNA (dsRNA) virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). The safety of orally administered acid-resistant IBDV strain R903/78 reverse engineered viral drug candidate was demonstrated in 10 stage IV cancer patients who exhausted all conventional therapy. Following repeated oral administration of the virus up to 10⁹ infectious units (IU)/ dose, only mild flu-like side effects were reported in some patients. Proof-of-principle efficacy was demonstrated in an early COVID-19 patient who was successfully treated with 3x10⁶ IU of an attenuated IBDV vaccine. A small scale dose-finding Phase I safety study is proposed.

The holistic approach of One Health, which sees human, animal, plant, and environmental health as a unit, rather than discrete parts, requires not only interdisciplinary cooperation, but standardized methods for communicating and archiving data, enabling participants to easily share what they have learned and allow others to build upon their findings.Ongoing work by NCBI and the GenomeTrakr project illustrates how open data platforms can help meet the needs of federal and state regulators, public health laboratories, departments of agriculture, and universities. Here we describe how microbial pathogen surveillance can be transformed by having an open access database along with Best Practices for contributors to follow. First, we describe the open pathogen surveillance framework, hosted on the NCBI platform. We cover the current community standards for WGS quality, provide an SOP for assessing your own sequence quality and recommend QC thresholds for all submitters to follow. We then provide an overview of NCBI data submission along with step by step details. And finally, we provide curation guidance and an SOP for keeping your public data current within the database. These Best Practices can be models for other open data projects, thereby advancing the One Health goals of Findable, Accessible, Interoperable and Re-usable (FAIR) data.

The aquaculture sector has become increasingly reliant on soybean meal (SBM) and soy-derived proteins, because of their large abundance, low price and favorable amino acid profile. However, for Atlantic salmon, a major aquaculture species, the inclusion of soybean meal, and soy protein concentrate (SPC) in certain combinations has adverse impacts on its gut health and welfare. This study evaluated two enhanced SBM targeting improved gut health for inclusion in freshwater phase salmon diets, enzyme pre-treatment (ETS) and addition of fructose oligosaccharide (USP), respectively in comparison to untreated soybean meal (US) and fish meal (FM). The impact on growth performance, gut microbiome, and behaviors relevant to welfare was investigated. Both enhancements of SBM were found to support comparable growth performance to FM. Both targeted treatments altered the gut microbiome community. Fish fed SBM showed a tendency for more reactive behavior compared to those fed the FM-based control. All fish had a similarly low response to elicited stress, although ETS fed fish responded more actively than those fed the US diet. SBM fed fish also had lower repeatability of behavior, which may have implications for welfare. Both enhancements provide a promising basis to optimize the application of this widely used protein source.

This study applies a cluster analysis to identify typical physical activity (PA) and sedentary behaviour (SB) patterns in people with chronic obstructive pulmonary disease (COPD) before starting pulmonary rehabilitation (PR). We implemented an observational design which assessed baseline data on objectively measured PA and SB from the STAR (Stay Active after Rehabilitation) study. 355 persons wore a accelerometer (Actigraph wGT3X) for seven days before the start of their PR. Sociodemographic and disease-related parameters were assessed at the start of PR. We applied cluster analysis and compared groups applying univariate variance analyses. Data was available for 326 persons (31.6% women; age ø = 58 yr.). Cluster analysis revealed four movement clusters with distinct PA and SB patterns: sedentary non-movers (28.5%), sedentary occasional movers (41.7%), sedentary movers (19.6%), and sedentary exercisers (10.1%). The four clusters showed very different levels of moderate PA before rehabilitation (Ø daily minutes: 9; 28; 38; 70). Notably, all four clusters displayed considerably long average sitting time per day (Ø daily minutes: 644; 561; 490; 446). The groups differed significantly in disease-related parameters of GOLD severity, FEV1, CAT, and 6-Min-Walk-Test. In addition to PA promotion, PR programs should consider the reduction of sitting time as a valuable goal.

Background: The microbiome of the ocular surface has been characterised, but only limited in-formation is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed next generation sequencing (NGS) of 16S rDNA genes in aqueous hu-mor. Methods: Aqueous humor was sampled from three patients during cataract surgery. Air swabs, patient’s and healthy donor conjunctival swab served as controls. Following DNA extraction, the V3 and V4 hypervariable regions of the 16S rDNA gene were amplified and sequenced fol-lowed by denoising. The resulting Amplicon Sequence Variants were matched to a subset of the Ribosomal Database Project 16S database. The deduced bacterial community was then statis-tically analysed. Results: DNA content in all samples was low (0-1.49 ng/µl) but sufficient for analysis. Main phyla in all samples were Acinetobacteria (48%), Proteobacteria (26%), Firmicutes (14%), Acidobac-teria (8%) and Bacteroidetes (2%). Patients conjunctival control samples and anterior chamber fluid showed similar patterns of bacterial species containing many waterborne species. Non-disinfected samples showed a different bacterial spectrum than the air swab sample. Conclusions: The data confirm the existence of an ocular surface microbiome. A distinct intraoc-ular microbiome was not discernable from the background, suggesting the absence of an intra-ocular microbiome in normal eyes.

Life-threatening inflammatory conditions such as acute respiratory distress syndrome or sepsis often go hand in hand with severe vascular leakage. During inflammation, endothelial cell integrity and intact barrier function are crucial to limit leukocyte and plasma extravasation. Prostaglandin D₂ (PGD₂) is a potent inflammatory lipid mediator with vasoactive properties. It has been suggested that PGD^­₂ is involved in the regulation of endothelial barrier function; however, it is unclear whether this is also true for primary human pulmonary microvascular endothelial cells. Furthermore, as PGD₂ is a highly promiscuous ligand, we set out to determine which receptors are important in human pulmonary endothelial cells. In the current study, we found that PGD₂ and the DP1 agonist BW245c potently strengthened pulmonary and dermal microvascular endothelial cell barrier function and protected against thrombin-induced barrier disruption. Yet surprisingly, these effects were mediated only to a negligible extent via DP1 receptor activation. In contrast, we observed that the EP4 receptor was most important and mediated the barrier enhancement by PGD₂ and BW245c. These data demonstrate a novel mechanism by which PGD₂ may modulate inflammation and emphasizes the role of EP4 receptors in human endothelial cell function.

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

The zoonotic disease anthrax caused by the endospore-forming bacterium Bacillus anthracis is very rare in Germany. In the state of Bavaria, the last case occurred in July of 2009 resulting in four dead cows. In August of 2021, the disease reemerged after heavy rains, killing one gestating cow. Notably, both outbreaks affected the same pasture, suggesting a close epidemiological connection. B. anthracis could be grown from blood culture and the presence of both virulence plasmids (pXO1 and pXO2) were confirmed by PCR. Also, recently developed diagnostic tools enabled rapid detection of B. anthracis cells and nucleic acids directly in clinical samples. The complete genome of the strain isolated from blood, designated BF-5, was DNA-sequenced and phylogenetically grouped within the B.Br.CNEVA clade that is typical for European B. anthracis strains. The genome was almost identical to BF-1, the isolate of 2009, separated only by three single nucleotide polymorphisms on the chromosome, one on plasmid pXO2 and three indel-regions. Further, B. anthracis DNA was detected by PCR from soil-samples taken from spots, where the cow had fallen onto the pasture. New tools based on phage receptor binding proteins enabled the microscopic detection and isolation of B. anthracis directly from soil-samples. These environmental isolates were genotyped and found to be SNP-identical to BF-1. Therefore, it seems that the BF-5 genotype is currently the prevalent one at the affected premises. The contaminated area was subsequently disinfected with formaldehyde.

For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins and carbohydrates in their seeds, distinctly dominate modern agronomic practice. Indeed, these plants play an essential role in the food industry and fuel production. Therefore, the seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, not only seed development and germination, but also age- and stress-related alterations in seed vigor, longevity, nutritional value and safety can be addressed by a broad panel of analytical, biochemical and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes, accompanying plant development, senescence and response to biotic or environmental stress. Among individual methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. Here we discuss the main methodological approaches employed by seed proteomics in the context of physiological changes related to seed development, ageing and response to environmental stress.

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

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

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

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

Natural products have long played a major role in medicine and science. The garden snail Cornu aspersa is a rich source of biologically active natural substances which might be an important source for new drugs to treat human disease. Based on our previous studies seven fractions containing compounds with Mw &lt;3 kDa, &lt;10 kDa, &lt;20 kDa, &gt;20 kDa, and between 3-5 kDa, 5-10 kDa, and 10-30 kDa were purified from the mucus of C. aspersa and analyzed by tandem mass spectrometry (MALDI-TOF/TOF). Seventeen novel peptides with potential antibacterial activity have been identified by de novo MS/MS sequencing using tandem mass spectrometry. The different fractions were tested for antibacterial activity against Gram─ (Pseudomonas aureofaciens and Escherichia coli) and Gram+ (Brevibacillus laterosporus) bacterial strains as well anaerobic bacterium Clostridium perfringens. These results revealed that the peptide fractions exhibit a predominant antibacterial activity against B. laterosporus, the fraction with Mw 10 – 30 kDa against E. coli, another peptide fraction &lt;20 kDa against P. aureofaciens, and the protein fraction &gt;20 kDa against the bacterial strain C. perfringens. The discovery of new antimicrobial peptides (AMPs) from natural sources is of great importance for public health due to their effective antimicrobial activities and low resistance rates.

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair successful vaccination of elderly people. Thus, improved vaccination strategies specifically adapted to an aged immune system are required. We characterized a recombinant MVA expressing a stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, protection correlated with potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation as clinical candidate vaccines in elderly people to overcome limitations of age-dependent immunosenescence.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.