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

The study presents an updated overview of the 14 non-endemic threatened Crop Wild Relatives (CWR) in Italy: Aegilops biuncialis, Ae. uniaristata, Ae. ventricosa, Asparagus pastorianus, Beta macrocarpa, Brassica insularis, B. montana, Crambe hispanica subsp. hispanica, C. tataria subsp. tataria, Ipomoea sagittata, Lathyrus amphicarpos, L. palustris, Vicia cusnae and V. serinica. Geographical distribution, ecology (with plant communities and habitat 92/43/EEC aspects), genetics (focused on gene pools), property, and in situ and ex situ conservation were analyzed. In addition, with the aim of their protection and valorization, specific actions are recommended.

Augmented reality (AR) provides an opportunity for mobile fitness applications to show users real-time feedback on their current fitness activity. For such applications, it is essential to accurately track the user’s current fitness activity using available mobile sensors, such as inertial measurement units (IMUs). Convolutional neural networks (CNNs) have been shown to produce strong results in different time series classification tasks, including the recognition of activities of daily living. However, fitness activities can present unique challenges to the human activity recognition task (HAR), including greater similarity between individual activities and fewer available data for model training. In this paper, we evaluate the applicability of CNNs to the fitness activity recognition task (FAR) using IMU data and determine the impact of input data size and sensor count on performance. For this purpose, we adapted three existing CNN architectures to the FAR task and designed a fourth CNN variant, which we call the scaling fully convolutional network (Scaling-FCN). We designed a preprocessing pipeline and recorded a running exercise data set with 20 participants, in which we evaluated the respective recognition performances of the four networks, comparing them with three traditional machine learning methods commonly used in HAR. On our data set, all CNN architectures significantly outperformed traditional machine learning methods, reaching up to 97.14±1.36% classification accuracy on the test set for ResNet. Whereas a reduced input data size invariably led to a performance loss, removing specific sensors improved the performance of all CNN architectures, with our Scaling-FCN reaching the highest accuracy of 99.86±0.11%. Our results suggest that CNNs are generally well suited for fitness activity recognition, and noticeable performance improvements can be achieved if sensors are dropped selectively.

This study explores the determinants of ICO success, where success is defined as the amount of capital a project was able to raise. ICOs are a tool for startups in the blockchain ecosystem to raise early capital with relative ease. The market for ICOs has grown at a rapid pace since its start in 2013. We analyze a unique dataset of 278 projects that finished their ICOs by August 2017 to assess determinants of funding success that we derive from the crowdfunding and venture capital literature. Our results show that ICOs exhibit similarities to classical crowdfunding and venture capital markets. Specifically, we identify resemblances in determinants of funding success regarding human capital characteristics, business model quality, project elaboration and social media activity.

Human-to-human communication via the computer is mainly done using a keyboard or microphone. In the field of Virtual Reality (VR), where the most immersive experience possible is desired, the use of a keyboard contradicts this goal, while the use of a microphone is not always desirable (e.g. silent commands during task force training) or simply not possible (e.g. if the user has a hearing loss). Data gloves help to increase immersion within the VR as they correspond to our natural interaction. At the same time, they offer the possibility to accurately capture hand shapes, such as those used in non-verbal communication (e.g. thumbs up, okay gesture, ...) and in sign language. In this paper, we present a hand shape recognition system using Manus Prime X data gloves, including data acquisition, data preprocessing, and data classification to enable nonverbal communication within VR. We investigate the impact on accuracy and classification time of using an Outlier Detection and a Feature Selection approach in our data preprocessing. To obtain a more generalized approach, we also studied the impact of artificial Data Augmentation, i.e., we create new artificial data from the recorded and filtered data to augment the training dataset. With our approach, 56 different hand shapes could be distinguished with an accuracy of up to 93.28%. With a reduced number of 27 hand shapes, an accuracy of up to 95.55% could be achieved. Voting Meta-Classifier (VL2) has proven to be the most accurate, albeit slowest, classifier. A good alternative is Random Forest (RF), which was even able to achieve better accuracy values in a few cases and was generally somewhat faster. Outlier Detection has proven to be a effective approach, especially in improving classification time. Overall, we have shown that our hand shape recognition system using data gloves is suitable for communication within VR.

Poly(dA:dT) tracts cause nucleosome depletion in many species, e.g., at promoters and replication origins. Their intrinsic biophysical sequence properties make them stiff and unfavorable for nucleosome assembly, as probed by in vitro nucleosome reconstitution. The mere correlation between nucleosome depletion over poly(dA:dT) tracts in vitro and in vivo inspired an intrinsic nucleosome exclusion mechanism in vivo. However, we compile here published and new evidence that this correlation does not reflect mechanistic causation. 1) Nucleosome depletion over poly(dA:dT) in vivo is not universal, e.g., very weak in S. pombe. 2) The energy penalty for incorporating poly(dA:dT) tracts into nucleosomes is modest (<10%) relative to ATP hydrolysis energy abundantly invested by chromatin remodelers. 3) Nucleosome depletion over poly(dA:dT) is much stronger in vivo than in vitro if monitored without MNase and 4) actively maintained in vivo. 5) S. cerevisiae promoters evolved a biased poly(dA) versus poly(dT) distribution. 6) Nucleosome depletion over poly(dA) is directional in vivo. 7) The ATP dependent chromatin remodeler RSC preferentially and directionally displaces nucleosomes towards 5’ of poly(dA). Especially bias and directionality would not be expected for an intrinsic mechanism. Together, this argues for a mechanism where active and species-specific read out of intrinsic sequence properties, e.g., by remodelers, shapes nucleosome occupancy.

Background: In past years recreational diving has attracted more and more interest and among such divers an increasing number of diabetic divers. However, there is limited research on the accuracy of CGM systems under hyperbaric conditions and consistently diving guidelines make little reference to the use of CGM. Subject and Method: This exploratory study collected blood glucose samples of one diabetic diver over four dives and assessed the deviation of intersitial glucose values from two CGM systems based on 33 samples. A notable step of this method is to collect the data from actual dives under water. Results: The results indicate that a) under hyperbaric conditions of up to 2bar additional pressure and b) after decompression both CGM systems work comparably accurate as indictated by the manufacturer under normal conditions. This has been checked in terms of MARD and Clarke Error Grid Distirbution. Conculsion: For diabetic divers the results suggest they may take CGM monitors with them on dives to react to potential hypoglycemic events before they occur, i.e. when it is still safe to supplement glucose. For dive guidelines the results imply that these could reference CGM for dive planning and monitoring during the dive to increase divers‘ safety. For research this exploratory confirms the current hypothesis that neither increased pressure nor saltwater have an effect on blood glucose and the functioning of CGM systems. Further research may include additional sampling (number and depth) and more elaborate blood glucose measurement. The experimental setup applied is an efficient way to test further CGM systems.

This paper reviews the management of the COVID-19 crisis and the difficulty of cost estimation model, comparing centralized management or bureaucratic government coaction and the agile market alternative or spontaneous social coordination. This is a study of Political Economy and Health Economics from the perspective of Austrian Economics. We describe and compare the al-ternative models, which are adapted to the current crisis. The analysis is based on the theorem of the impossibility of the economic calculation under coactive systems, and other principles of economy. In this context we pay also attention to collateral problems of the centralized and coac-tive management. Finally we propose a solution based on dynamic efficiency and the constitutions of wellbeing economics

A new requirement for the manufacturing companies in Industry 4.0 is to be flexible with respect to changes in demands, requiring them to react rapidly and efficiently on the production capacities. Together with the trend to use Service-Oriented Architectures (SOA), this requirement induces a need for agile collaboration among supply chain partners, but also between different divisions or branches of the same company. In order to address this collaboration challenge, we~propose a novel pragmatic approach for the process analysis, implementation and execution. This~is achieved through sets of semantic annotations of business process models encoded into BPMN 2.0 extensions. Building blocks for such manufacturing processes are the individual available services, which are also semantically annotated according to the Everything-as-a-Service (XaaS) principles and stored into a common marketplace. The optimization of such manufacturing processes combines pattern-based semantic composition of services with their non-functional aspects. This is achieved by means of Quality-of-Service (QoS)-based Constraint Optimization Problem (COP) solving, resulting in an automatic implementation of service-based manufacturing processes. The produced solution is mapped back to the BPMN 2.0 standard formalism by means of the introduced extension elements, fully detailing the enactable optimal process service plan produced. This approach allows enacting a process instance, using just-in-time service leasing, allocation of resources and dynamic replanning in the case of failures. This proposition provides the best compromise between external visibility, control and flexibility. In this way, it provides an optimal approach for business process models' implementation, with a full service-oriented taste, by implementing user-defined QoS metrics, just-in-time execution and basic dynamic repairing capabilities. This paper presents the described approach and the technical architecture and depicts one initial industrial application in the manufacturing domain of aluminum forging for bicycle hull body forming, where the advantages stemming from the main capabilities of this approach are sketched.

Numerous approaches address over-fitting in neural networks: by imposing a penalty on the parameters of the network (L1, L2, etc); by changing the network stochastically (drop-out, Gaussian noise, etc.); or by transforming the input data (batch normalization, etc.). In contrast, we aim to ensure that a minimum amount of supporting evidence is present when fitting the model parameters to the training data. This, at the single neuron level, is equivalent to ensuring that both sides of the separating hyperplane (for a standard artificial neuron) have a minimum number of data points — noting that these points need not belong to the same class for the inner layers. We firstly benchmark the results of this approach on the standard Fashion-MINST dataset, comparing it to various regularization techniques. Interestingly, we note that by nudging each neuron to divide, at least in part, its input data, the resulting networks make use of each neuron, avoiding a hyperplane completely on one side of its input data (which is equivalent to a constant into the next layers). To illustrate this point, we study the prevalence of saturated nodes throughout training, showing that neurons are activated more frequently and earlier in training when using this regularization approach. A direct consequence of the improved neuron activation is that deep networks are now easier to train. This is crucially important when the network topology is not known a priori and fitting often remains stuck in a suboptimal local minima. We demonstrate this property by training a network of increasing depth (and constant width): most regularization approaches will result in increasingly frequent training failures (over different random seeds) whilst the proposed evidence-based regularization significantly outperforms in its ability to train deep networks.

There is much discussion regarding the Sustainable Development Goals’ (SDGs) capacity to promote inclusive development. While some argue that they represent an opportunity for goal-led alignment of stakeholders and evidence-based decision-making, other voices express concerns as they perceive them as a techno-managerial framework that measures development according to quantitatively defined parameters and does not allow for local variation. We argue that the extent to which the positive or negative aspects of the SDGs prevail depends on the monitoring system’s ability to account for multiple and intersecting inequalities. The need for sub-nationally (urban) representative indicators poses an additional methodological challenge – especially in cities with intra-urban inequalities related to socio-spatial variations across neighbourhoods. This paper investigates the extent to which the SDG indicators’ representativeness could be affected by inequalities. It does so by proposing a conceptual framing for understanding the relation between inequalities and SDG monitoring, which is then applied to analyse the current methodological proposals for the indicator framework of the “urban SDG”, Goal 11. The outcome is a call for 1) a more explicit attention to intra-urban inequalities, 2) the development of a methodological approach to “recalibrate” the city-level indicators to account for the degree of intra-urban inequalities, and 3) an alignment between methodologies and data practices applied for monitoring SDG 11 and the extent of the underlying inequalities within the city. This would enable an informed decision regarding the trade-off in indicator representativeness between conventional data sources, such as censuses and household surveys, and emerging methods, such as participatory geospatial methods and citizen-generated data practices.

Concrete is the most commonly used construction material due to its various advantages, such as versatility, familiarity, strength and durability and it will continue to be in demand far into the future. However, with today’s sensitivity to the environmental protection, this material is facing unprecedented challenges due to its high greenhouse gas emission mainly during cement production. This paper investigates one of the promising cement replacement materials, alkali activated cement (AAC) concrete. Being produced mainly from byproduct materials and having a comparable structural performance to conventional concrete, AAC concrete has a potential to transform the construction industry. Mechanical properties such as compressive and flexural strength and the relationship between them are studied. Different source materials such as fly ash (FA), ground granulated blast furnace slag (GGBS), silica fume (SF) and Metakaolin (MK) are used. The effect of the source materials and the activator solutions on the concrete performance is studied. Furthermore, the freeze-thaw resistance of the concrete is studied. The results of the study showed that the behavior of AAC depends highly on the source material combinations as well as type used. The effect of the alkaline solution is also dependent on the source material used. Mixes with higher GGBS content in general showed the highest strength while mixes with MK showed the highest flexural strength. The results from the freeze-thaw test showed that proper design of AAC concrete with a lower water content is critical to achieve a good resistance.

This paper presents the results of a recent study that was conducted with a number of German municipalities/cities. Based on the obtained and briefly presented recommendations emerging from the study, the authors propose the concept of an Urban Data Space (UDS), which facilitates an eco-system for data exchange and added value creation thereby utilizing the various types of data within a smart city/municipality. Looking at an Urban Data Space from within a German context and considering the current situation and developments in German municipalities, this paper proposes a reasonable classification of urban data that allows to relate the various data types to legal aspects and to conduct solid considerations regarding technical implementation designs and decisions. Furthermore, the Urban Data Space is described/analyzed in detail, and relevant stakeholders are identified, as well as corresponding technical artifacts are introduced. The authors propose to setup Urban Data Spaces based on emerging standards from the area of ICT reference architectures for Smart Cities, such as DIN SPEC 91357 “Open Urban Platform” and EIP SCC. Thereby, the paper walks the reader through the construction of an UDS based on the above mentioned architectures and outlines all the goals, recommendations and potentials, which an Urban Data Space can reveal to a municipality/city.

Virtual validation of radar sensor models is becoming increasingly important for the safety validation of adf. Therefore, methods for quantitative comparison of radar measurements in the context of model validation need to be developed. This paper presents a novel methodology for accessing and quantifying validation measurements of radar sensor models. This method uses edf and the so-called dvm to effectively quantify deviations between distributions. By applying this metric, the study measures the consistency, reproducibility and repeatability of radar sensor measurements. Different interfaces and different levels of detail are investigated. By comparing the radar signals from real world experiments where different objects are present, valuable insights are gained into the performance of the sensor. In particular, the research extends to assessing the impact of varying rain intensities on the measurement results, providing a comprehensive understanding of the sensor’s behaviour under these conditions. This holistic approach significantly advances the evaluation of radar sensor capabilities and enables the quantification of the maximum required quality of radar simulation models.

In the rapidly evolving landscape of AI-supported programming education, there's a growing interest in leveraging such tools to support students helping about what good code makes out. This study investigates the impact of ChatGPT on code quality among part-time undergraduate students enrolled in introductory Java programming courses. With no prior Java experience, students from two separate groups completed identical programming exercises emphasizing coding conventions and code quality. Utilizing static code analysis tools, we assessed adherence to a common coding convention ruleset and calculated cyclomatic and cognitive complexity metrics for submitted code. Our comparative analysis highlights significant improvements in code quality for the ChatGPT-assisted group (treatment group), with marked reductions in rule violations and both cyclomatic and cognitive complexities. Specifically, the treatment group demonstrated greater adherence to coding standards, with fewer violations across several rules, and produced code with lower complexity. These results suggest that ChatGPT can be a valuable tool in programming education, aiding students in writing cleaner, less complex code and better adhering to coding conventions. However, the study's limitations, including the small sample size and the novice status of the participants, necessitate further research with larger, more diverse populations and in different educational contexts.

The process industry is confronted with rising demands for flexibility and efficiency. One way to achieve this are modular process plants that consist of pre-manufactured modules with their own decentralized intelligence. Plants are then composed of these modules as unchangeable building blocks and can be easily re-configured for different products. Condition monitoring of such plants is necessary, but available solutions are not applicable. The authors suggest an approach in which model-based symptoms are derived from few measurements and observers that are based on manufacturer knowledge. The comparisons of redundant observers lead to residuals that are classified to obtain symptoms. These symptoms can be communicated to the plant control and are inputs to an easily adaptable diagnosis. The implementation and validation at a modular mixing plant showcases the feasibility and the potential of this approach.

The adaptive immune system in vertebrates comes in two flavors. Historically, adaptive immunity focused on the study of immunoglobulins (also referred to as Ig-based antibodies herein); more recently, jawless vertebrates were found to use an entirely different class of proteins for their adaptive immunesystem. Specifically, these organisms express variable lymphocyte receptors (so called VLR antibodies) that create diversity based on the rearrangement of leucine-rich repeats. Meanwhile, various, naturally occurring repeat motifs have been used as building blocks for the design of artificial binding scaffolds which, among others, include designed ankyrin repeat proteins (DARPins). Such binding scaffolds are also referred to as non-Ig-based antibodies or non-Ig scaffolds herein). DARPins display several benefits such as a low molecular weight (~15 kDa), high thermal stability, high specificity and affinity, versatility (e.g., in terms of valency and multi-specificity), speedy preclinical development, low production costs and, thus, bear the potential to not only complement existing therapeutic Ig-based antibodies but also open up novel therapeutic strategies. The first generation DARPin therapeutic abicipar pegol has completed two Phase III studies in 2020 while several other DARPin drug candidates are currently undergoing clinical validation. Most recently, the rapid development of tri-specific SARSCoV-2 DARPin therapeutics showcases the immense potential of recombinant repeat proteins in adopting quickly e.g., new forms of target neutralization that a single Ig-based antibody cannot afford. Here, we highlight the design principles of repeat proteins in general and summarize in detail the continuous advancements of the DARPin scaffold that made it one of the most promising antibody mimetics to date. This review provides an overview of current and emerging applications of DARPins as both a research tool and therapeutic drug that can match or even surpass Ig-based antibody applications.

Haemodynamic indices are widely used in clinical practice for deciding on a particular type of treatment. Low quality of the CT data and tachycardia complicate interpretation of the measured or simulated values. In this work, we present a novel approach for evaluating resistances in terminal coronary arteries. Using 14 measurements from 10 patients, we show that this algorithm retains the accuracy of 1D haemodynamic simulations in less detailed (truncated) geometric models of coronary networks. We also apply the variable systole fraction model to study the effect of elevated heart rate on the values of FFR, CFR and iFR. We conclude that tachycardia may produce both overestimation or underestimation of coronary stenosis significance.

Oracles have been suggested as a vital piece of infrastructure necessary to allow blockchain-based smart contracts to reach their full potential by interacting with real-world data. This paper begins by providing an approachable entry point to the oracle problem and the current landscape of existing solutions. From there, we provide an overview of published research to narrow down unexplored research directions and derive questions for interviews. Finally, the results of 15 unstructured expert interviews are presented and discussed. The focus here is the industry landscape of oracle projects, opportunities for innovation, and challenges needing to be overcome.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Balínt Syndrome is an acquired disorder manifesting in the inability to recognize several objects at once (simultagnosia), inaccurate visually guided limb movements despite intact motor function (optic ataxia) and the inability to make accurate voluntary saccades to visual targets despite demonstrating unrestricted range of eye movements (ocular motor apraxia). Here we report the first case of a patient presenting with Balínt Syndrome caused by a platelet-derived growth factor receptor A mutation (PDGFRA)-induced Hypereosinophilic Syndrome (HES).

Based on a measuring system to determine levels of spatial organization in 2D polygons (homogeneous or heterogeneous partition of defined areas) lying on principles of regularity, we propose the entropy term linked to the concept of “information”, from the “information theory field”, in order to obtain an information measurement regarding a quantity of or amount of information in the architecture of complex 2D biological organizations. The term “quantity” does not refer to the amount of data (size), but to the probability of a geometrical basic pattern within a set of possible statistical configurations regarding levels of homogeneity and heterogeneity. It is this notion of information that is important in information theory, and measures of information in units of bits, what we propose to use for measuring quantities of organization in the architecture of complex geometrical systems. Two complex systems are tested, biological and non biological in order to obtain experimental results, which are verified with the evaluation criteria “entropy”. Experimental results show that the lowest levels of information and entropy, in addition with low rates of heterogeneity and high rates of homogeneity are particular features of geometrical organizations in biological systems.

The macro-litter (plastic) sea bottom pollution of 14 city harbors and marinas in North Africa and in the western Baltic Sea was investigated using a new simple mobile underwater camera system. The study was complemented by a harbor manager survey and 3D-hydrodynamic transport simulations. The average pollution in German marinas was 0.1 particles/m² sea floor (0.04–1.75). The pollution in North African marinas on average was 7 times higher (0.7 particles/m²) and exceeded 3 particles/m² in city center harbors. The resulting &gt;100,000 litter particles per harbor indicate the existence of a problem. With 73%-74%, plastic particles are dominating. Existing legal and management frameworks explain the lack of plastic bottles and bags on sea floors in Germany and are one reason for the lower pollution levels. Items that indicate the role of untreated sewage water were not found. Harbor festivals seem not to be quantitatively relevant for open sea bottom pollution. Our method tends to underestimate the pollution level. Model simulations indicate that storms can cause litter reallocations and sediment cleanings. However, marina sea floor monitoring is recommendable, because it addresses pollution hot-spots, is cost-effective and takes place close to emission sources. Further, the effectiveness of land-based pollution reduction measures can easily be assessed.

The influence of cuff inflations on nighttime measurements during 24h ambulatory blood pressure (BP) measurements is unknown. We investigated the potential effect of cuff-inflations on asleep parameters using measurements taken simultaneously with a cuffless device using pulse-transit-time (PTT). On the first day of measurement, standard cuff-based 24h BP and cuf-fless measurements were simultaneously performed on right and left arms (CUFF/PTT-D). 1-2 days after the first measurement, the cuffless device was worn alone (PTT-D). Only data from the cuffless device was analyzed. The following mean asleep parameters were analyzed: systolic and diastolic BP, arousals, sleep efficiency, total arousals, arousal per hour and desaturations. 21 in-dividuals were prospectively enrolled. Mean (SD) age was 47(±15) years and 57% were female. Mean systolic asleep BP for the during CUFF/PTT-D and during PTT-D were 131(±21) and 131(±26) mmHg respectively. Mean diastolic asleep BP values during CUFF/PTT-D and during PTT-D were 80(±14) and 84(±14) mmHg respectively (p=0.860, p=0.100 respectively). Systolic and diastolic asleep mean difference was 0.1 (±18.0) and -3.6 (±9.8) mmHg, respectively. There were significantly more total arousals during PTT-D (p=0.042). There was no significant difference seen in sleep efficiency (p=0.339) or desaturations (p=0.896) between the two measurements. We could not show any significant impact from cuff inflations during asleep PTT-D measurements.

To increase the power density of the electromechanical drive train of wind turbines, journal bearings can be used as planetary gear bearings instead of rolling bearings. This technological change presents new challenges. For example, wind turbine drive systems are subject to dynamic and low-speed operating conditions which can lead to an accelerated abrasive wear of the journal bearings. In addition, oil supply failure or peak loads due to wind gusts and grid and power converter faults could potentially result in catastrophic failure due to adhesive wear in a very short time. Such operating characteristics are, therefore, critical regarding the journal bearing wear lifetime and must be considered in the design. The successful implementation of journal bearings in wind turbines depends on a reliable estimation of adhesive and abrasive wear. In this paper, five different models for the wear calculation of journal bearings are evaluated regarding their suitability of wear calculation of planetary gear bearings in wind turbines. For this purpose, the following evaluation criteria were defined: parameter uncertainty, parametrization effort, in particular number of parameters, parameterization method and load case dependency of parameters and calculation effort. In order to be able to evaluate the wear models, the wear models are numerically implemented and the wear of a test journal bearing is exemplarily calculated under load conditions, which are comparable to load conditions in a wind turbine. Relevant influences from the wind turbine system such as lubricant, material and manufacturing dependent surface influences like roughness and hardness are considered. The wear models are evaluated with respect to their fulfillment of the defined criteria. The resulting evaluation allows the selection of a wear model that can be used to calculate the wear of planetary gear journal bearings in wind turbines, considering the available input variables.

Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.

The constant increase in volume and wide variety of available Internet of Things (IoT) devices leads to highly diverse software and hardware stacks, which opens new avenues for exploiting previously unknown vulnerabilities. The ensuing risks are amplified by the inherent IoT resource constraints both in terms of performance and energy expenditure. At the same time, IoT devices often times generate or collect sensitive, real-time data used in critical application scenarios (e.g. health monitoring, transportation, smart energy, etc.). All these factors combined make IoT networks a primary target and potential victims for malicious actors. In this paper, we present a brief overview of existing attacks and defense strategies against urban IoT networks. The goal of this work is twofold: First, it presents a summary of some of the common attack vectors and the corresponding solutions available in the research literature. Then, the paper lays out a theoretical plan and a corresponding pipeline of steps (i.e. development and implementation process) for the design and application of the solutions encountered throughout the course of the research efforts. The end goal of following this plan is the deployment of the proposed IoT security measures in a real-world urban IoT infrastructure.

The extent of access to energy of displaced populations in settlements and camps in Africa is largely 14 unknown. A multitude of contextual factors, such as the location and the characteristics of housing, 15 the legal status, the socio-cultural background, and the availability of humanitarian and public ser- 16 vices impact the living conditions and the needed energy services. Limitations in accessing energy 17 services have direct, multilayered, and far-reaching implications, including impacts on health, nu- 18 trition, education, protection, and livelihood. The objective of this article is to contribute to a more 19 comprehensive overview of the current state of energy access in displacement contexts on the Afri- 20 can continent by identifying and utilizing existing data. After a screening of the vast and various 21 available information, setting up of a database, consolidating the gathered data as well as assessing 22 the quality through a quality assessment method, the currently available information is visualized 23 and discussed. Considerable differences in the access to electricity for displaced persons across the 24 countries are found. For both electricity and clean cooking, the availability for displaced persons 25 ranges from nearly no access at all up to an access rate of 100%. More strikingly, the results also 26 show that besides South Africa and countries in the Maghreb region, the access to both clean cook- 27 ing and electricity for displaced persons is very low. At the same time, the fragmented data availa- 28 bility, the poor data quality, and the questionable expediency of available data allows neither solid 29 theoretical conclusions nor planning of effective practical implementation measures. Novel inter- 30 disciplinary research, conceptual frameworks and indicators are needed for the purpose of compa- 31 rability and consistency. Future research has the potential to more comprehensively capture the 32 current state of access to energy in displacements contexts and in a next step to examine how energy 33 is interwoven in the lives of displaced people to derive a set of more detailed context-sensitive en- 34 ergy indicators. It is essential that the concerned persons, the displaced persons themselves are in- 35 cluded in the research in a meaningful way.

Mapping drought from space using, e.g., surface soil moisture (SSM), has become viable in the last decade. However, state of the art SSM retrieval products suffer from very poor coverage over northern latitudes. In this study, we propose an innovative drought indicator with a wider spatial and temporal coverage than that obtained from satellite SSM retrievals. We evaluate passive microwave brightness temperature observations from the Soil Moisture and Ocean Salinity (SMOS) satellite as a surrogate drought metric, and introduce a Standardized Brightness Temperature Index (STBI). The STBI is validated against drought indices from a land surface data assimilation system (LDAS-Monde), two satellite dervied SSM indices and a standardized precipitation index. Finally, we evaluate the STBI against the before mentioned drought indices in a case study of the 2018 Nordic drought. The STBI is found to be superior to the drought index created from satellite derived SSM in both spatial and temporal coverage over the Nordic region. Our results indicate that when compared to drought indices from precipitation data and a land data assimilation system, the STBI is able to capture the 2018 drought onset, severity and extent. Thus, the STBI index could provide additional information for drought monitoring in regions where the SSM retrieval problem is difficult.

We propose that the high energy Cosmic Ray particles around the spectral turn-down commonly called the {\it knee} and up to the upturn, commonly called the {\it ankle}, mostly come from Blue Super Giant star explosions. At the upturn, i.e. the {\it ankle}, Cosmic Rays probably switch to another source class, most likely extragalactic sources. To show this we recently compiled a set of Radio Supernova data to list the magnetic field, shock speed and radius scale (Biermann et al. 2018) \cite{Biermann18}. Using particle acceleration theory at shocks, those numbers can be transformed into characteristic {\it knee} and {\it ankle} energies. Without adjusting any free parameters both of these observed energies are directly indicated by the supernova data. We now proceed to the next step in the argument, and use the Supernova Remnant data of the starburst galaxy M82. Assuming that they are Blue Supergiant star explosions, the shock will race to their outer edge with a magnetic field that follows ${B (r) \, r \, \sim \, const.}$. We argue that the shock runs through the entire magnetic plasma wind region at full speed all the way out to the wind-shell, which is of order parsec scale. The speed is observed to be $\sim \, 0.1 \, c$ at about ${10^{16} \, {\rm cm}}$ radius in the plasma wind. This demonstrates how Blue Supergiant star explosions can provide the Cosmic Ray particles across the {\it knee} and up to the {\it ankle} energy range. The data from the CREAM (Cosmic Ray Energetics and Mass Experiment) mission will test this cosmic ray concept which is reasonably well grounded in two independent radio supernova data sets. The next step in developing our understanding is to obtain accurate Cosmic Ray data near to the {\it knee}, and use unstable isotopes of Cosmic Ray nuclei at high energy to probe the "piston" driving the explosion. We plan to combine these data with the physics of the budding black hole which is probably forming in each of these stars to learn more.

The interlaminar strength of mechanically interlocked polymer-metal-interfaces is strongly dependent on the surface structure of the metal component. Therefore, this contribution assesses the suitability of the fractal dimension for quantification of the surface structure as well as interlaminar strength prediction of aluminum/polyamide 6 polymer-metal-hybrids. Seven different surface structures, manufactured by blasting, combined blasting and etching, thermal spraying and laser ablation, are investigated. The experiments are carried out on a novel butt-bonded hollow cylinder testing method that allows shear and tensile strength determination with one specific specimen geometry. The fractal dimension of the metal surfaces is derived from cross-sectional images. For comparison, the surface roughness slope is determined and related to the interlaminar strength. Finally, a fracture analysis is conducted. For the investigated material combination, the experimental results indicate that the fractal dimension is an appropriate measure for predicting the interlaminar strength

Plant cells are omnipotent and breeding of new varieties can be achieved by protoplast fusion. Such fusions can be achieved by treatment with poly(ethylene glycol) or by applying an electric field. Microfluidic devices allow for controlled conditions and targeted manipulation of small batches of cells down to single cell analysis. To provide controlled conditions for protoplast fusions and achieve high reproducibility, we developed and characterized a microfluidic device to reliably trap few of Arabidopsis thaliana protoplasts and induced a cell fusion by controlled addition of poly(ethylene glycol) (PEG, with a molecular weight of 6000). Experiments were conducted to determine the survival rate of isolated protoplasts in our microfluidic system. Afterwards, PEG induced fusion was studied. Our results indicate that the following fusion parameters had significant impact on the fusion efficiency and duration: PEG concentration, osmolarity of solution, and flow velocity. PEG concentration below 10% led to only partial fusion. Osmolarity of the PEG fusion solution was found to strongly impact the fusion process; complete fusion of two source cells sufficiently took part in slightly hyper osmotic solutions, whereas iso-osmotic solutions led to only partial fusion at 20% PEG concentration. We observed accelerated fusion for higher fluid velocities. Up to this study, it was common sense that fusion is one directional, i.e. once two cells were fused into one cell they stay fused. Here, we present for the first time reversible fusion of protoplasts. Our microfluidic device paves the way to a deeper understanding on the kinetics and processes of cell fusion.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

In the field of quality analysis of food and flavoring products, gas chromatography – quadrupole mass spectrometry – ion mobility spectrometry (GC-QMS-IMS) is a powerful technique for the simultaneous detection of volatile organic compounds (VOC) by both QMS and IMS. GC is an established technique for the separation of complex VOC-rich foods such as beverages, dairy and fruit products as well as flavorings in general. While the subsequent detection by IMS features soft ionization of fragile compounds (e.g., terpenes) with characteristic drift times, MS provides the analytes’ m/z-values for database substance identification. A limitation of the prominently used static headspace-based GC-QMS-IMS systems is the substantially higher sensitivity of IMS in comparison to full scan QMS, which results in the detection of relevant VOC only in IMS, but not in the QMS analyzer. The present study describes a new prototypic trapped-headspace (THS)-GC-QMS-IMS setup, with optimized active flow regulation, able to gain valuable data of both detectors. This ultimately allows the combination of a soft ionization with m/z values obtained from database-searchable electron ionization (EI) spectra and as such, offers a substantial advantage in fields of quality control. The new setup features aligned retention times for IMS and MS and sufficient signal intensities for QMS and IMS. The analytical setup was evaluated with a set of mango puree samples from various provenances and the data was evaluated by suitable machine learning approaches. The results demonstrate that THS-GC-QMS-IMS allows for the classification of mango purees from different cultivars and can be a promising alternative method for authenticity control of food, flavors, and beverages.

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

The energy transition towards renewable and more decentral power production triggers the need for grid and storage expansion on all voltage levels. Today's power system planning focuses on certain voltage levels or spatial resolutions. In this work we present an open source software tool eGo which is able to optimize grid and storage expansion throughout all voltage levels in a developed top-down approach. System costs are minimized by applying a linear optimal power flow considering the grid infrastructure of the extra-high and high-voltage (380 to 110 kV) level. Hence, the common differentiation of transmission and distribution grid is partly dissolved, integrating the high-voltage level into the optimization problem. Consecutively, optimized curtailment and storage units are allocated in the medium voltage grid in order to lower medium and low voltage grid expansion needs, that are consequently determined. Here, heuristic optimization methods using the non-linear power flow were developed. Applying the tool on future scenarios we derived cost-efficient grid and storage expansion for all voltage levels in Germany. Due to the integrated approach storage expansion and curtailment can significantly lower grid expansion costs in medium and low voltage grids and at the same time serve the optimal functioning of the overall system. Nevertheless, the cost-reducing effect for the whole of Germany was marginal. Instead, the consideration of realistic, spatially differentiated time series lead to substantial overall savings.

The threats of climate change and the sustainable supply of clean energy are global challenges that require an international approach to the energy supply. Utilizing the wind and solar energy potential of regions where these renewable sources are especially viable to produce hydrogen by means of water electrolysis represents an attractive option to counter the above-mentioned challenges. Within the scope of this techno economic analysis of a worldwide hydrogen supply infrastructure based on renewable energy, selected regions are assessed on the basis of their wind or solar energy potential. In contrast to established analyses of hydrogen infrastructures, this paper introduces a worldwide allocation approach to the supply hydrogen from strong wind and solar regions to different demand regions on the premise of a global supply cost minimum. The allocation results show a significant dependence of hydrogen export volumes and the oversea transport distances of potential trading partners. Hence, the transnational trading flows of hydrogen derived from wind and solar energy are concentrated in continental regions.

The aim of this work is to develop a method to produce spherical biopolymer-based aerogel particles, which is capable for scale up in the future. Therefore, jet cutting method is suggested. Amidated pectin and sodium alginate were used as precursor (1–3 wt. % solution) for particle production via jet cutting. Gelation was realized via two methods: internal setting method (using calcium carbonate particles as cross-linker and citric and acidic acid for pH adjustment) and diffusion method (in calcium chloride solutions). Gel particles were subjected to solvent exchange to ethanol and consequent supercritical drying with CO₂. Spherical aerogel particles with narrow particle size distribution in the range of 400 to 1500 µm and with specific surface area of around 500 m²/g could be produced. Overall, it can be concluded that jet cutting method is suitable for aerogel particle production, although the shape of the particles is not perfectly spherical in all cases. However, parameter adjustment might lead to even better shaped particles in further work. Moreover, the biopolymer-based aerogel particles synthesized in this study were tested as humidity absorber in drying units for home appliances, particularly for dishwashers. It could be shown that for several cycles of absorption and desorption of humidity aerogel particles are stable with an absorption capacity of around 20 wt. %.

The analysis of microscopy images has always been an important yet time consuming process in in materials science. Convolutional Neural Networks (CNNs) have been very successfully used for a number of tasks, such as image segmentation. However, training a CNN requires a large amount of hand annotated data, which can be a problem for material science data. We present a procedure to generate synthetic data based on ad-hoc parametric data modelling for enhancing generalization of trained neural network models. Especially for situations where it is not possible to gather a lot of data, such an approach is beneficial and may enable to train a neural network reasonably. Furthermore, we show that targeted data generation by adaptively sampling the parameter space of the generative models gives superior results compared to generating random data points.

The synthesis of chelating NHC complexes with considerable π-acceptor properties can be a challenging task. This is due to the dimerization of free carbene ligands, the moisture sensitivity of reaction intermediates or reagents, and challenges associated with the workup procedure. Herein, we report a general route using transmetalation from magnesium NHCs. Notably, this route gives transition metal complexes in quantitative conversion without the formation of byproducts. Accordingly, it allows for the facile access to transition metal complexes where the conventional routes via the free or lithium coordinate carbene, the silver complexes, or in situ metalation in dimethyl sulfoxide (DMSO) fail. We therefore propose transmetalation from magnesium NHCs as a convenient and general route to NHC complexes.

Non-rigid registration presents a significant challenge in the domain of point cloud processing. The general objective is to model complex non-rigid deformations between two or more overlapping point clouds. Applications are diverse and span multiple research fields, including registration of topographic data, scene flow estimation, and dynamic shape reconstruction. To provide context, we begin with a general introduction to the topic of point cloud registration, including a categorization of methods. Next, we introduce a general mathematical formulation for point cloud registration and extend it to address non-rigid registration. A detailed discussion and categorization of existing approaches to non-rigid registration follows. We then introduce our own method where the usage of piece-wise tricubic polynomials for modeling non-rigid deformations is proposed. Our method offers several advantages over existing methods. These advantages include easy control of flexibility through a small number of intuitive tuning parameters, a closed-form optimization solution, and an efficient transformation of huge point clouds. We demonstrate our method through multiple examples that cover a broad range of applications, with a focus on remote sensing applications - namely, the registration of Airborne Laser Scanning (ALS), Mobile Laser Scanning (MLS), and Terrestrial Laser Scanning (TLS) point clouds. The implementation of our algorithms is open source and can be found on GitHub.

Disorders of swallowing often lead to pneumonia when material enters the airways (aspiration). Flexible Endoscopic Evaluation of Swallowing (FEES) plays a key role in the diagnostics of aspiration but is prone to human errors. An AI-based tool could facilitate this process. Recent non-endoscopic/non-radiologic attempts to detect aspiration using machine-learning approaches have led to unsatisfying accuracy and show black box characteristics. Hence, for clinical users it is hard to trust in these model decisions. Our aim is to introduce an explainable artificial intelligence (XAI) approach to detect aspiration in FEES. Our approach is to teach the AI about the relevant anatomical structures like the vocal cords and the glottis based on 92 annotated FEES videos. Simultaneously, it is trained to detect bolus that passes the glottis and becomes aspirated. During testing, the AI successfully recognized glottis and vocal cords, but could not yet achieve satisfying aspiration detection quality. Albeit detection performance has to be optimized, our architecture results in a final model that explains its assessment by locating meaningful frames with relevant aspiration events and by highlighting the suspected bolus. In contrast to comparable AI tools, our framework is verifiable, interpretable and therefor accountable for clinical users.

Equal-Channel Angular Pressing (ECAP) is a method used to introduce severe plastic deformation into a metallic billet without changing its geometry. In special cases strain localization occurs and a pattern consisting of regions with high and low deformation (so-called shear and matrix bands) can emerge. This paper studies this phenomenon numerically adopting two-dimensional finite element simulations of one ECAP pass. The mechanical behavior of aluminum is modeled using phenomenological plasticity theory with isotropic or kinematic hardening. The effects of the two different strain hardening types are investigated numerically by systematic parameter studies: While isotropic hardening only causes minor fluctuations in the plastic strain fields, a material with high initial hardening rate and sufficient strain hardening capacity can exhibit pronounced localized deformation after ECAP. The corresponding finite element simulation results show a regular pattern of shear and matrix bands. This result is confirmed experimentally by ECAP-processing of AA6060 material in a severely cold worked condition, where microstructural analysis also reveals the formation of shear and matrix bands. Excellent agreement is found between the experimental and numerical results in terms of shear and matrix band width and length scale. The simulations provide additional insights regarding the evolution of the strain and stress states in shear and matrix bands.

For the purpose of improve the sustainability of products sold in the EU, Digital Product Passports is a mandatory solution. These passports would systematically gather information about products, such as detailing the materials involved to aid recycling and remanufacturing efforts, or recording the emissions produced throughout the manufacturing process. The overall goal is the establishment of a circular economy in the EU. Current research on Digital Product Passports is focused on collating content for sector-specific applications. However, achieving sustainability goals through Digital Product Passports will require new methods and technical solutions for digital collaboration between supply chain participants, especially in the manufacturing sector. Collaborative work on Digital Product Passports requires trust and traceability in data and access management to ensure privacy over the data contained. One way to enable this securely and confidentially is through the use of blockchain technology, in which stored data cannot be concealed, which is key to the traceability of digital product data documentation. This paper therefore presents a concept for the implementation of generically applicable cross-industry blockchain-based digital product passports. To this end, generic supply chain processes have been abstracted and condensed into the architecture of smart contracts. Great attention is paid to the establishment of traceability as well as privacy through the selection of the blockchain technology Secret Network in combination with Gaia-X functionalities. An illustrative use case for digital product passports in manufacturing is used to demonstrate the applicability of the presented concept. In this use case information about the digital nameplate and carbon footprint is exchanged securely and confidentially in a multi-tenant supply chain network based on the Industry 4.0 infomation model of the Asset Administration Shell.

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

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

In this work we have critically reviewed the processes in high-temperature sublimation growth of graphene in Ar atmosphere using enclosed graphite crucible. Special focus is put on buffer layer formation and free charge carrier properties of monolayer graphene and quasi-freestanding monolayer garphene on 4H-SiC. We show that by introducing Ar at different temperatures, TAr one can shift to higher temperatures the formation of the buffer layer for both n-type and semi-insulating substrates. A scenario explaining the observed suppresed formation of buffer layer at higher TAr is proposed and discussed. Increased TAr is also shown to reduce the sp3 hybridization content and defect densities in the buffer layer on n-type conductive substrates. Growth on semi-insulating substrates results in ordered buffer layer with significantly improved structural properties, for which TAr plays only a minor role. The free charge density and mobility parameters of monolayer graphene and quasi-freestanding monolayer graphene with different TAr and different environmental treatment conditions are determined by contactless terahertz optical Hall effect. An efficient annealing of donors on and near the SiC surface takes place in intrinsic monolayer graphene grown at 2000∘C, and which is found to be independent of TAr. Higher TAr leads to higher free charge carrier mobility parameters in both intrinsically n-type and ambient p-type doped monolayer graphene. TAr is also found to have a profound effect on the free hole parameters of quasi-freestanding monolayer graphene. These findings are discussed in view of interface and buffer layer properties in order to construct a comprehensive picture of high-temperature sublimation growth and provide guidance for growth parameters optimization depending on the targeted graphene application.

The delineation of the clinical target volumes (CTVs) for radiation therapy is time-consuming, requires intensive training and shows high inter-observer variability. Supervised deep learning methods depend heavily on consistent training data, thus state-of-the-art research focuses on making CTV labels more homogeneous and strictly bounding them to current standards. International consensus expert guidelines standardize CTV delineation by conditioning the extension of the clinical target volume on surrounding anatomical structures. Training strategies that directly following the construction rules given in the expert guidelines or the possibility to quantify the conformance of manually drawn contours with the guidelines are still missing. 71 anatomical structures that are relevant for CTV delineation in head and neck cancer patients according to the expert guidelines were segmented on 104 CT scans to assess the possibility to automate their segmentation by state-of-the-art deep learning methods. nnU-Net models were trained to automatically segment those 71 structures on planning CT scans. We report the DICE, HD and sDICE for 71 + 5 anatomical structures for most of which no previous segmentation accuracies have been reported. For those structures, for that prediction values have been reported, our segmentation accuracy matched or exceeded the reported values. The predictions from our models were always better than those predicted by the TotalSegmentator. The sDICE with 2mm margin was larger than 80% for almost all structures. Individual structures with decreased segmentation accuracy are analyzed and discussed with respect to their impact on the CTV delineation following the expert guidelines. No deviation is expected to affect the rule-based automation of the CTV delineation.

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

In this study we present gas-phase fluorination as a method to create a thin LiF layer on Li6.5La3Zr1.5Ta0.5O12 (LLZTO). We compare these fluorinated films with LiF films produced by RF-magnetron sputtering, where we investigated the interface between the LLZTO and the deposited LiF showing no formation of a reaction layer. Furthermore, we investigate the ability of this LiF layer as a protection layer against Li2CO3 formation in ambient air. By this we show that Li2CO3 formation is absent at the LLZTO surface after 24 h in ambient air supporting the protective character of the formed LiF films and hence could enhance the handling of LLZTO in air for battery production. With respect to the use within hybrid electrolytes consisting of LLZTO and a mixture of polyethylene oxide (PEO) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) we also investigated the interface between the formed LiF films and a mixture of PEO LiTFSI by X-ray photoelectron spectroscopy (XPS) showing decomposition of the LiTFSI at the interface.

Targeted radioisotope-guided sentinel lymph node dissection (sLND) has shown high diagnostic accuracy in prostate cancer (PCa). To overcome the downsides of the radioactive tracers, magnetometer-guided sLND using superparamagnetic iron oxide nanoparticles (SPIONs) was successfully applied in PCa. This prospective study (SentiMag Pro II, DRKS00007671) determined the diagnostic accuracy of magnetometer-guided sLND in intermediate- and high-risk PCa. Fifty intermediate- or high-risk PCa patients (PSA≥10 ng/ml and/or Gleason score ≥7; median PSA 10.8 ng/ml, IQR 7.4–19.2 ng/ml) were enrolled. After intraprostatic SPIONs injection a day earlier, patients underwent magnetometer-guided sLND and eLND, followed by radical prostatectomy. SLNs were detected in vivo and in ex vivo samples. Diagnostic accuracy of sLND was assessed using eLND as the reference. SLNs were detected in all patients (detection rate 100%), with 447 SLNs (median 9, IQR 6–12) being identified and 966 LNs (median 18, IQR 15-23) being removed. Thirty-six percent (18/50) of patients had LN metastases (median 2, IQR 1–3). Magnetometer-guided sLND had 100% sensitivity, 97.0% specificity, 94.4% positive predictive value, 100% negative predictive value, 0.0% false negative rate, and 3.0% additional diagnostic value (LN metastases only in SLNs outside the eLND template). In vivo, one positive SLN/LN-positive patient was missed, resulting in a sensitivity of 94.4%. In conclusion, this new magnetic sentinel procedure has high accuracy for nodal staging in intermediate- and high-risk PCa. The reliability of intraoperative SLN detection using this magnetometer system requires verification in further multicentric studies.

FacioScapuloHumeral Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders, and is linked to the inappropriate expression of the DUX4 transcription factor in adult muscles. The deregulated molecular network causing FSHD skeletal muscle dysfunction and pathology is still not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4 induced cell death. In this study, we further explore the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knock-down in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

Active-case finding (ACF) using chest X-ray is an essential method of finding and diagnosing TB cases that may be missed in Indonesia's routine TB case finding. This study compares active and passive TB case-finding strategies. A retrospective study of TB case notification was conducted. Data between January 1 and December 31, 2021, was used. The population in this study were TB cases notified from Kulon Progo District health facilities, including those found through routine activities or active-case finding. A total of 255 TB cases were diagnosed in Kulon Progo in 2021, and 106 (41.6%) were bacteriologically confirmed. The TB patients' mean age was 46.3 (SD 21.4, range 0-85 years). The majority of cases were male (58.8%) and mostly among people aged 16-60 years old (63.5%). ACF diagnosed 91 TB cases (35.7% total cases, 91/255). The proportion of clinical TB cases (n=68, 74.7%) among those found through ACF was higher than found through passive-case finding. Use of chest X-ray in ACF likely contributed to the detection of a higher proportion of clinical TB than bacteriologically confirmed.

Pathogen fitness landscapes change when transmission cycles establish in non-native environments or spill over into new vectors and hosts. The introduction of Leishmania infantum in the Americas into the Neotropics during European colonization represents a unique case study to investigate mechanisms of ecological adaptation of this important parasite. Defining the evolutionary trajectories that drive L. infantum fitness in this new environment are of great public health importance as they will allow unique insight into pathways of host/pathogen co-evolution and their consequences for region-specific changes in disease manifestation. This review summarizes current knowledge on L. infantum genetic and phenotypic diversity in the Americas and its possible role in the unique epidemiology of VL in the New World. We highlight the importance of appreciating adaptive molecular mechanisms in L. infantum to understand the parasites’ successful establishment on the continent.

Shielding agents are commonly used to shield polyelectrolyte complexes, e.g. polyplexes, from agglomeration, precipitation in complex media, like blood, and thus enhance their circulation times in vivo. Since up to now primarily poly(ethylene glycol) (PEG) has been investigated to shield non-viral carriers for systemic delivery, we report on the use of polysarcosine (pSar) as a potential alternative for steric stabilization. A redox-sensitive, cationizable lipo-oligomer structure (containing two cholanic acids attached via a bioreducible disulfide linker to an oligoaminoamide backbone in T-shape configuration) was equipped with azide-functionality by solid phase supported synthesis. After mixing with small interfering RNA (siRNA), lipopolyplexes formed spontaneously and were further surface-functionalized with polysarcosines. Polysarcosine was synthesized by living controlled ring-opening polymerization using an azide-reactive dibenzo-aza-cyclooctyne-amine as an initiator. The shielding ability of the resulting formulations was investigated with biophysical assays and by near-infrared fluorescence bioimaging in mice. The modification of ~100 nm lipopolyplexes was only slightly increased upon functionalization. Cellular uptake into cells was strongly reduced by the pSar shielding. Moreover, polysarcosine-shielded polyplexes showed enhanced blood circulation times in bioimaging studies compared to unshielded polyplexes and similar to PEG-shielded polyplexes. Therefore, polysarcosine is a promising alternative for the shielding of non-viral, lipo-cationic polyplexes.

Pure orbital blowout fractures occur within the confines of the internal orbital wall. Restoration of orbital form and volume is paramount to prevent functional and esthetic impairment. The anatomical peculiarity of the orbit has encouraged surgeons to develop implants with customized features to restore its architecture. This has resulted in worldwide clinical demand for patient-specific implants (PSIs) designed to fit precisely in the patient's unique anatomy. Fused filament fabrication (FFF) three-dimensional (3D) printing technology has enabled the fabrication of implant-grade polymers such as Polyetheretherketone (PEEK), paving the way for a more sophisticated generation of biomaterials. This study evaluates the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the relevant design, biomechanical, and morphological parameters. The performance of the implants is studied as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predict the high durability of the implants, and the maximum deformation values were under one-tenth of a millimeter (mm) domain in all the implant profile configurations. The circular patterned implant (0.9 mm) had the best performance score. The study demonstrates that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor.

Tungsten fibre-reinforced tungsten composites (Wf/W) have been in development to overcome the inherent brittleness of tungsten as one of the most promising candidate for the first wall and divertor armour material in a future fusion power plant. As the development of Wf/W continues, the fracture toughness of the composite is one of the main design drivers. In this contribution the efforts on size upscaling of Wf/W based on Chemical Vapour Deposition (CVD) is shown together with fracture mechanical tests of two different size samples of Wf/W produced by CVD. Three-point bending tests according to ASTM E399 for brittle materials were used to get a first estimation of the toughness. A provisional fracture toughness value of up to 346MPam1/2 was calculated for the as-fabricated material. As the material does not show a brittle fracture in the as-fabricated state, the J-Integral approach based on the ASTM E1820 was additionally applied for this state. A maximum value of the J-integral of 41kJ/m2 (134,8MPam1/2) was determined for the largest samples. Post mortem investigations were employed to detail the active mechanisms and crack propagation.

Road marking recognition is of great importance for the deployment of automated driving systems and for already existing driver line-keeping assistance systems. For proper and reliable function of machine vision systems that include LiDAR and camera, road markings must be visible to them to facilitate planning of driving trajectory. In this study, LiDAR intensity and the number of LiDAR points collected from a field analysis of two road markings systems reflectorised with premium and standard glass beads were analysed. In the lateral direction, it was demonstrated that the use of premium glass beads for road markings lead to 56% higher LiDAR intensity and 14% more LiDAR points captured than in case of standard road markings. In the longitudinal direction, premium road markings showed less distance attenuation, which is seen as advantageous for trajectory planning by machine version systems. The outcomes of this study offer insights for road infrastructure decision-makers, developers of automated driving systems, and researchers in the field of transportation technology.

Long-acting injectable antipsychotics (LAIs) offer many benefits to patients with schizophrenia spectrum disorder (SSD). They are used with very different frequencies due to questions of eligibility or patients’ and prescribers’ attitudes towards LAI use. We assessed the prescribing rates of LAIs in a large academic psychiatric hospital with public service mandate in Switzerland and compared them with other countries and health care systems. To our knowledge this study is the first to investigate the inpatient LAI-use in Europe. Medical records of all patients diagnosed with SSD discharged from the Clinic of Adult Psychiatry of the University Hospital of Psychiatry Zurich over a 12-month period from January to December 2019 were evaluated regarding the prescribed antipsychotics at the time of discharge. The rates of use of LAIs among all patients and among patients receiving LAI eligible antipsychotic substances were assessed retrospectively. We assessed records of 885 patients with SSD. Among all cases 13.9% received an LAI. Among patients who received antipsychotic medication that was eligible for LAI use 28.3% (n=434) received an agent as LAI. These included paliperidone palmitate (69.9%), aripiprazole monohydrate (14.6%), risperidone (4.9%) and first-generation LAIs (9.8%). Compared to international frequencies of LAI administration, the prescription rate of LAIs in SSD patients was low. Further studies will evaluate patient- and prescriber-related reasons for this low rate.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Based on a measuring system to determine the statistical heterogeneity of individual polygons we propose a method to use polygonal shape patterns as a source of data in order to determine the Shannon entropy of biological organizations. In this research, the term entropy is a particular amount of data related with levels of spatial heterogeneity in a series of different geometrical meshes and sets of random polygons. We propose that this notion of entropy is important to measure levels of information in units of bits, measuring quantities of heterogeneity in geometrical systems. In fact, one important result is that binarization of heterogeneity frequencies yields a supported metric to determine geometrical information from complex configurations. Thirty-five geometric aggregates are tested; biological and non-biological, in order to obtain experimental results of their spatial heterogeneity which is verified with the Shannon entropy parameter defining low particular levels of geometrical information in biological samples. Geometrical aggregates (meshes) include a spectrum of organizations ranging from cell meshes to ecological patterns. Experimental results show that a particular range (0.08 and 0.27) of information is intrinsically associated with low rates of heterogeneity. We conclude it as an intrinsic feature of geometrical organizations in multi-scaling biological systems.

The unsustainability of the services related to water, sanitation and hygiene in informal settlements in Sub-Saharan Africa services is deeply embedded in current societal and governance structures, cultures and practices; it is context-dependent and involves numerous actors with different interests. The field of sustainability transitions research addresses such persistent and large scale societal challenges, with transition management being one of its widely applied governance approach. By drawing on an analysis of the root causes of unsustainability and unreliability of WASH services in three case studies in Sub-Saharan Africa (Arusha-Tanzania, Dodowa-Ghana, Kampala-Uganda), we explore how a transition management approach can be designed to support a transition towards sustainable Water, Sanitation and Hygiene (WASH) in Sub-Saharan Africa. We distinguish the following contextual dimensions related to the unsustainability of WASH services: a) Multiplicity of WASH practices, structures and arrangements, b) Governance capacities for WASH services and maintenance, c) Landownership for sustainable access to WASH, d) Public participation in decision-making related to WASH, e) socio-economic structures governing access to WASH. These dimensions prompt the identification of conceptual and application challenges for transition management. Based on these challenges, recommendations were formulated for the design of a prescriptive transition management process that is not only functional but also emancipatory of character.

Based on the demographic shift and the related challenges resulting from the growing number of elderly and persons with chronic diseases, the idea of smart home that supports its inhabitants in the daily life, gains importance. The purpose of this paper was to examine in a prototypic Ambient Assisted Living environment if users after interaction with different health-supporting applications intend to use such in the future. Two experimental studies exemplary show possible applications of home-integrated technology that can support, assist and accompany the target group in different contexts, and examine to what extent participants are willing to future use such sophisticated technology at home. The results show that people in general, but especially the old and chronically ill ones are quite fascinated of health-supporting ambient technology and the majority intends to use such ambient assistance in the future (study I). Moreover, serious games for healthcare are shown as a hedonic use of technology in smart homes that have a great potential to retain or improve the physical health, mobility and the overall well-being of the inhabitants (study II). The article provides two examples of ambient technology to leverage the demographic change and presents important user factors for facilitating high user acceptance.

Background and Objectives: Ultrasound (US) is a non-invasive tool for the in-vivo detection of peripheral nerve alterations. Materials and Methods: In this study we applied nerve US to assist the discrimination between the spectrum of Amyotrophic Lateral Sclerosis (ALS, n=11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n=5) and genetically confirmed Charcot-Marie-Tooth disease (CMT, n=5). All participants and n=15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. Nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms and nerve conduction studies. Analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (T) magnetic resonance neurography (MRN). Results: Patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. Blood flow was greatest in CIDP, and higher than in CMT, ALS and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP and CMT, even in small sample sized groups. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants along the disease groups.

This study investigates the land surface temperature (LST) distribution from thermal infrared data for analyzing the characteristics of surface coverage using the Vegetation-Impervious-Soil (VIS) approach. A set of ten images, obtained from Landsat-5 Thematic Mapper, between 2001 and 2010, were used to study the urban environmental conditions of 47 neighborhoods of Porto Alegre city, Brazil. Porto Alegre has had the smallest population growth rate of all 27 state capitals in the last two decades in Brazil, with an increase of 11.55% in inhabitants from 1,263 million in 1991 to 1,409 million in 2010. We applied the environmental Kuznets curve (EKC) theory in order to test the influence of the economically-related scenario on the spatial nature of social-environmental arrangement of the city at neighborhood scale. Our results suggest that the economically-related scenario exerts a non-negligible influence on the physically driven characteristics of the urban environmental conditions as predicted by EKC theory. The linear inverse correlation R2 between household income (HI) and LST is 0.36 and has shown to be comparable to all other studied variables. Future research may investigate the relation between other economically-related indicators to specific land surface characteristics.

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis additionally we previously found higher initial AP drop after cardiac surgery is associat-ed with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) 314 patients with active isolated left-sided infective endocarditis at the De-partment of Cardiac Surgery (Medical University of Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative day 1-7, postoperative days 14, and 30). Patients were categorized ac-cording to relative alkaline phosphatase drop (≥30% vs. <30%). (3) The rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p=0.001 and 6.7 vs. 15.6%; p=0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p=0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mor-tality 3.0 vs. 10.6%; p=0.010) and long-term mortality (p=0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

The androgen/androgen receptor (AR)-signaling axis plays a central role in the development and growth of prostate cancer (PCa) cells. Upon androgen-binding the AR dimerizes with another AR, translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. In consequence treatments for locally advanced or metastatic PCa are commonly based on androgen deprivation therapies (ADT). Unfortunately, the clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. In the clinic failure of ADT is often characterized by the synthesis of a C-terminally truncated, constitutively active AR splice variant, termed AR-V7. In contrast to AR, the constitutively active AR-V7 does no longer need androgenic stimuli for nuclear entry and/or dimerization. The goal of the present study was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology (NanoBiT) structural complementation assay under androgen stimulation and deprivation conditions. Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 localize in the nucleus. However, after 15 min of androgen stimulation, all AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers localized in the nucleus. In this way, we can show an androgen-regulated interaction between AR-FL and AR-V7 at forming heterodimers that localize in the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus. Treatment with enzalutamide diminished the luminescence of AR-FL homodimers and AR-FL/AR-V7 heterodimers but not AR-V7/AR-V7 homodimers.

Thymomas (TH) are a unique group of heterogeneous tumors of the thymic epithelium. In particular, the subtypes B2 and B3 tend to be aggressive and metastatic. Radical tumor resection remains the only curative option for localized tumors, while more advanced TH require multimodal treatment. Deep sequencing analyses have failed to identify known oncogenic driver mutations in TH, with the notable exception of the GTF2I mutation, which occurs predominantly in type A and AB TH. However, there are multiple alternative non-mutational mechanisms (e.g., perturbed thymic developmental programs, metabolism, non-coding RNA networks) that control cellular behavior and tumorigenesis through deregulation of critical molecular pathways. Here, we attempted to show how the results of studies investigating such alternative mechanisms could be integrated into a current model of TH biology. This model could be used to focus ongoing research and therapeutic strategies.

Development of new neurotherapeutics is strongly depending on appropriate animal model chosen in preclinical studies. A cuprizone model is an effective tool for studying demyelination and re-myelination processes in the brain, but BBB integrity in cuprizone model is still a topic for debate. Several publications claim that BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could be explained by the increased BBB permeability. In our work we aim to analyze permeability of BBB for different macromolecules, particularly, antibody-conjugates in cuprizone-intoxicated mice. We compared the traditional approach using Evans blue injection with following dye extraction and detection of antibody-conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in cuprizone model. First, we validated our model of demyelination by detecting changes in gene expression of myelin basic protein and proteolipid protein, and by performing MRI and histological analysis. Our results suggest that the methods with better sensitivity were able to detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that ques-tioned BBB integrity in cuprizone model and demonstrate possibility for delivery of anti-body-conjugates to demyelinated corpus callosum

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Patients with low back pain often have deficits in trunk stability. For this reason, many patients receive physiotherapy treatment, which represents an enormous socio-economic burden. Training at home could reduce these costs. The prob-lem here is the lack of correction of the exercise execution. This feasibility study therefore investigates the applicability of a vibrotactile-controlled feedback system for trunk stabilization exercises. A sample of 13 healthy adults performed three trunk stabilization exercises. Exercise performance was corrected by physiotherapists using vibrotactile feedback. The NASA TLX questionnaire was used to assess the practicability of the vibrotactile feedback. The Nasa TLX questionnaire show a very low global workload M = 37.96 (SD =11.63). The quality of feedback perception was perceived as good by the subjects, varying between 76.9 % and 92.3 % depending on the body part. 80.8 % rated the feedback as helpful for their training. On the expert side, the results show a high rating of movement quality. The positive evaluations of the physiotherapists and the participants on the use of the vibrotactile feedback system indi-cate that such a system can reduce the trainees fear of independent training and support the users in their training. This could increase training adherence and long-term success.

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

The research field of two dimensional (2D) materials strongly relies on optical microscopy characterization tools to identify atomically thin materials and to determine their number of layers. Moreover, optical microscopy-based techniques also opened the door to study the optical properties of these nanomaterials. We present a comprehensive study of the differential reflectance spectra of 2D semiconducting transition metal dichalcogenides (TMDCs), MoS₂, MoSe₂, WS₂ and WSe₂, with thickness ranging from one layer up to six layers. We analyze the thickness-dependent energy of the different excitonic features, indicating the change in the band structure of the different TMDC materials with the number of layers. Our work provides a route to employ differential reflectance spectroscopy for determining the number of layers of MoS₂, MoSe₂, WS₂ and WSe₂.

Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic and Reston (RESTV) causing no severe disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with reduced inhibition of IFN-I signaling. We hypothesized that modification of eVP24-karyopherin alpha interface to make it similar to bVP24 would attenuate the ability to antagonize IFN-I response. We generated a panel of recombinant EBOVs containing single or combinations of point mutations in the eVP24-karyopherin alpha interface. Most of the viruses appeared to be attenuated in both IFN-I-competent 769-P and IFN-I-deficient Vero-E6 cells in the presence of IFNs. However, the R140A mutant grew at reduced levels even in the absence of IFNs in both cell lines, as well as in U3A STAT1 knockout cells. Both the R140A mutation and its combination with the N135A mutation caused almost complete inhibition of genome replication and transcription suggesting the role of these mutations in an IFN-I-independent attenuation. Additionally, we found that unlike eVP24, bVP24 does not inhibit interferon lambda 1 (IFN-λ1), which potentially explains the lower pathogenicity of BDBV relative to EBOV. Thus, the VP24 residues binding karyopherin alpha affect ebolavirus pathogenicity by IFN-I-dependent and independent mechanisms.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. Chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here we studied two synthetic PPAP-derivatives, PPAP 23 and PPAP 53, as to their antimicrobial activity. While PPAP 23 is insoluble in water, PPAP 53, the sodium salt, is water-soluble. In vitro, both compounds exhibited good and comparable activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae, even at high concentrations. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar neutralizing effect was also seen with serum albumin. In a septic arthritis model triggered by S. aureus PPAP23 decreased the formation of abscesses and bacterial load in kidneys, and in a mouse skin abscess model topical treatment with PPAP 53 resulted in an approximately two-fold reduction in S. aureus counts. PPAP 23 and PPAP 53 also showed high growth inhibiting activity against anaerobic Gram-positive pathogenic gut bacteria such as Clostridium perfringens and Clostridium difficile. Based on these results, we envision potential application of PPAP 23 and PPAP 53 in the topical treatment of wound infections with Gram+ pathogens, and their oral use in intestinal infections with C. difficile.

Osteoarthritis of the hand (HOA) is one of the most common musculoskeletal diseases affecting health. Osteophytes, documented by imaging procedures are often used as diagnostic criteria. The gold standard is the radiographic image, however, more sensitive and saver methods such as ultrasound are gaining in importance. We investigated the prevalence, grade and pattern of osteophytes by high resolution ultrasound investigation (US) in a population-based cross-sectional study. Factory workers were recruited at work. 26 finger joints of each participant were examined with US with grading the occurrence of osteophytes in a semiquantitative score ranging 0-3, increasing scores indicated larger osteophytes. 427 participants (mean age 53.5 years, range. 20-79 years) were investigated, resulting in 11,000 scored joints. At least one osteophyte was found in 4,546/11,000 (41.3%) joints or 426/427 (99.8%) participants but grade 2 or 3 osteophytes were seen in only 553 (5.0%) joints. The number of os-teophyte sum score increased with age (0.18/year of age increase, p<0.001). Distal interphalange-al joints (DIP) were predominantly affected with 61%, followed by proximal interphalangeal joints (PIP) with 48%, carpometacarpal joint 1 (CMC1) with 39% and metacarpophalangeal joints (MCP) with 16%. In conclusion, US is a feasible screening tool for osteophytes and HOA. Grade 1 osteophytes are a common finding in the working population when assessed by ultrasound and their prevalence is increasing with age. Prevalence of grade 2 or 3 osteophytes is less common and reflects clini-cal presence of HOA. Follow up investigations are necessary to recognize the predictive rele-vance of early osteophytes.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (N=271, 7 sites), to compare volumes of hippocampus, amygdala, and their subfields/nuclei between help-seeking subjects divided in risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2– 74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0– 71.9) for leave-one-site-out. Structural altera-tions of hippocampus and amygdala may not be as pronounced in young people at risk, nonetheless, ma-chine learning can predict estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity-modulation, desired radiation-induced effects observed in HNSCC, may also be observed as side-effects in healthy tissue e.g. the sternocleidomastoideus muscle (SCM). These side-effects (e.g. tissue fibrosis) depend on the interval between completion of RCT and restaging-CT. For salvage surgery, the optimal time window for surgery is currently postulated between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC-patients are sparse. The present study quantifies tissue alterations in SCM and paravertebral musculature (PVM) after RCT applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters 1) volume, 2) mean positivity of pixels (MPP) and 3) uniformity were extracted with mint lesionTM in the staging-CTs and restaging-CTs of 98 HNSCC-patients. Of these, 25 were female, the mean age was 62 (±9.6) years and 80.9% were UICC Stage IV. The mean restaging-interval was 55 (±28; range29-229) days. Only the mean volume significantly decreased after RCT from 9.0 to 8.4 and 96.5 to 91.9 ml for SCM and PVM, respectively (both p=0.007, both Cohen’s d=0.28). In addition, the mean body mass index (BMI) decreases from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p<0.001); Cohen's d = 0.9). The mean BMI-decrease significantly correlated with the volume decrease for SCM (r=0.27; p=0.007) and PVM (r=0.41; p<0.001). If t-test p-values were adjusted for the BMI-decrease, no significant change in volumes for SCM and PVM was observed (both p>0.05). The present data supports the postulated optimal interval for salvage surgery of 6 to 12 weeks. Irrespective of the remaining risk-benefit ratio of salvage surgery, the risk of additional surgical complications due to fibrosis is not supported by the present observations.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

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.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

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.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

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.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

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.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.