This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on healthy liver (HL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA-double strand breaks were investigated in irradiated and non-irradiated organotypic slice culture (OSC) and ex vivo samples by detection of Ki67 and γ-H2AX. OSC proved useful to determine dose-dependent effects on proliferation and DNA damage but appeared unsuited to test the chronotherapeutic approach. Irradiation of ex vivo samples was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on HL were minimal at ZT20. Ex vivo samples revealed disruption in daily variation and down-regulation of all investigated clock genes except Per1 in non-irradiated HCC as compared with HL. Irradiation affected rhythmic clock gene expression in HL and HCC at all ZTs except at ZT20. Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

Integrating triple bottom line (TBL) goals into supply chains (SCs) is a challenging task which necessitates the careful coordination of numerous stakeholders’ individual interests. Recent technological advancements can impact TBL sustainability by changing the design, structure and management of modern SCs. Blockchain technology enables immutable data records and facilitates a shared data view along the supply chain. The Physical Internet (PI) is an overarching framework that can be applied to create a layered and comprehensive view of the SC. In this conceptual paper I define and combine these technologies and derive several high-level research areas and research questions to investigate adoption, management as well as structural SC issues. I suggest a theory-based research agenda for the years to come that exploits the strengths of rigorous academic research, while remaining relevant for the industry. Furthermore, I suggest various well-established theories to tackle the respective research questions and provide specific directions for future research.

Background: Mitigating climate change requires fundamentally redesigned energy systems in which renewable energy sources ultimately replace fossil fuels such as natural gas. In this context, the question how and to which extent the gas sector can contribute to an increasingly climate-neutral future EU energy system is heavily debated among scholars, energy industry experts and policy makers. Methods: We take a two-step approach: We begin with a review of studies from energy industry and academia to discuss potential gas sector contributions from a holistic energy system design point of view; this is followed by a comprehensive discussion of technical potentials, micro-economic conditions and societal implications of renewable gas. We then enrich our findings with the results of an empirical focus group process. Results: The gas sector can not only contribute to balancing volatile renewable energy production but also enable the supply of renewable energy to end-users in gaseous form; based on existing infrastructure. This could reduce costs for society, increase public acceptance and ultimately speed up the energy system transformation. There is the theoretical technical potential to substitute major parts of natural gas with renewable gas of biogenic and synthetic nature. This, however, crucially requires a supportive policy framework like the one established for renewable electricity. Conclusion: Given the societal benefits and the competitiveness of renewable gas as compared to renewable alternatives, energy policy makers should incorporate renewable gas and the existing gas infrastructure in the future energy system framework. The objective should be an optimized interplay of various energy vectors and their infrastructure along the entire energy supply chain. This requires a level playing field for different renewable technologies across different policy areas and a form of public support that strikes the balance between facilitating the gradual substitution of natural gas by renewable gas while maintaining public acceptance for this transformation despite higher costs for end-users.: Given the societal benefits and the competitiveness of renewable gas as compared to renewable alternatives, energy policy makers should incorporate renewable gas and the existing gas infrastructure in the future energy system framework. The objective should be an optimized interplay of various energy vectors and their infrastructure along the entire energy supply chain. This requires a level playing field for different renewable technologies across different policy areas and a form of public support that strikes the balance between facilitating the gradual substitution of natural gas by renewable gas while maintaining public acceptance for this transformation despite higher costs for end-users.

Third and fourth-degree anal sphincter injuries are among the most severe traumas women can experience during childbirth, often leading to lifelong continence issues. Despite extensive research, current repair techniques are often inadequate, failing to provide long-term solutions. Women with previous severe injuries face a higher risk of recurrence in subsequent deliveries, making caesarean sections a safer option in many cases. The existing WHO classification system is outdated, as it doesn't account for injuries to muscles like the levator ani, which are crucial for continence. Effective repairs require skilled surgeons and often involve more than just fixing the sphincter. Smaller hospitals may not have the necessary expertise and resources for these complex repairs. Delaying repairs to allow specialists to perform them can be just as effective as immediate repairs. Comprehensive care that includes thorough anatomical knowledge and surgical skill is essential. As maternal age increases and birth rates decline, it's crucial for specialized centers to handle severe perineal injuries to ensure the best outcomes and long-term care for patients.

This article presents the results of technical and technological studies of the oil painting by the artist of German origin Werner Tübke “Hiroshima I" (1958). The creative heritage of the author has been little studied and represents scattered data on the technology of painting and artistic techniques. The aim of the work was to determine the artistic materials and painting technolo-gy described in his diaries, using the example of his only painting in Russia – “Hiroshima I". For this purpose, an integrated approach was used using non–invasive control methods - photo in the light of visible luminescence, infrared reflectography (IRR), radiography, portable X-ray fluorescence (XRF), as well as infrared-Fourier spectroscopy (FT-IR) and polarizing microsco-py using microprobes. As a result, the pigment composition of the painting layers was deter-mined, the painting technology was refined, and a previously unknown hidden portrait of Werner Tübke's father was revealed.

The morphologically variable moss Trichostomum brachydontium is very common in south and west Europe, particularly under Mediterranean and Atlantic climates. A morphological study was conducted alongside a molecular phylogenetic study based on nr ITS and cp rbcL regions in order to assess if T. brachydontium is an exceptionally polymorphic species as evidenced by the number of described infraspecific taxa from the last century or, alternatively, if it includes more than one species, and if so, to find the valid name for them. Phylogenetic analyses of both nuclear and chloroplast datasets show that there are four well-supported clades. While the ITS based tree is in good agreement with the morphological data, there are a few inconsistencies with reference to the rbcL tree; this may be explained by incomplete lineage sorting or by hybridization. The morphological survey revealed well-defined discriminate differences between the four phylogenetic lineages. The taxonomic conclusions include the recognition of four species: T. brachydontium s.s., T. herzogii (a new name proposed for var. cuspidatum), T. littorale and T. meridionale (a new name proposed for var. densum). Lectotypes are designated for T. brachydontium and T. littorale. Our results underline the ongoing need of integrative studies to examine further the underestimated diversity of the T. brachydontium complex in other regions.

The role of initial state (ISI) and final state (FSI) ion–ion interactions in heavy ion double charge exchange (DCE) reactions A(Z,N)→A(Z±2,N∓2) are studied in the context of double single charge exchange (DSCE) reactions given by sequential actions of the isovector nucleon–nucleon (NN) T–matrix. The second order DSCE reaction amplitude is investigated in momentum representation in a formulation, focused on the extraction of nuclear matrix elements under the conditions of strong initial state (ISI) and final state (FSI) interactions. In closure approximation and using the momentum representation, the reaction amplitude is finally separated into ISI/FSI distortion coefficients and reaction kernels and nuclear matrix elements. The ISI/FSI reaction kernels emerge as the result of the repeated scattering on the avoided volume, introduced by the imaginary parts of the ion–ion optical potential and acting as sinks for the quantal probability current. The closure approximation allows derive a set of induced effective two–body isotensor interactions, given by products of spin–scalar, spin–vector central and rank–2 spin–tensor interactions. The intermediate propagator plays a key role in establishing correlation between the DCE transitions in the projectile and target nucleus. The presented approach emphasizes the special features of DSCE reaction dynamics as proceeding like a system of two coupled isospin dipoles whose strengths are determined by the momentum-space form factors of the NN isovector interaction. The properties of the DSCE interaction form factors are investigated and the approach is applied to data.

We consider the problem of scheduling $n$ jobs with identical processing times and given release as well as delivery times on $m$ uniform machines. The goal is to minimize the makespan, i.e., the maximum full completion time of any job. This problem is well-known to have an open complexity status even if the number of jobs is fixed. We present a polynomial-time algorithm for the problem which is based on the earlier introduced algorithmic framework blesscmore (``branch less and cut more''). We extend the analysis of the so-called behavior alternatives developed earlier for the version of the problem with identical parallel machines and show how the earlier used technique for identical machines can be extended to the uniform machine environment if a special condition on the job parameters is imposed. The time complexity of the proposed algorithm is $O(\gamma m^2 n\log n)$, where $\gamma$ can be either $n$ or the maximum job delivery time $q_{\max}$. This complexity can even be reduced further by using a smaller number $\kappa<n$ in the estimation describing the number of jobs of particular types. However, this number $\kappa$ becomes only known when the algorithm has terminated.

In Low and Lower-Middle-Income countries, the prevalence of anemia in infancy remains high. In early childhood anemia cause irreversible cognitive deficits and represents a higher risk of child mortality. The consequences of anemia in infancy are a major barrier to overcome poverty traps. The aim of this study was to analyze based on a multi-level approach, different factors associated with anemia in children 6–23 m old based on recent available Standard Demographic Health Surveys (S-DHS). We identified 52 S-DHS that had complete information in all covariates of interest in our analysis between 2005 and 2015. We performed traditional logistic regressions and multilevel logistic regression analyses to study the association between hemoglobin concentrations and household, child, maternal, socio-demographic variables. In our sample, 70 % of the 6–23 m old children were anemic. Child anemia was strongly associated with maternal anemia, household wealth, maternal education and low birth weight. Children fed with fortified foods, potatoes and other tubers had significantly lower rates of anemia. Improving overall household living conditions, increasing maternal education, delaying childbearing and introducing iron rich foods at six months of age may reduce the likelihood of anemia at in toddlerhood.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

During the COVID-19 pandemic, individuals with symptoms other than cough or fever have refrained from seeking medical advice. However, a delay in treatment might lead to serious consequences. At the same time, digital health initiatives have emerged to overcome this bottleneck of healthcare. Herein, we report the results of a multi-center initiative using a combination of patient history and artificial intelligence (AI) to identify individuals with rare neuromuscular diseases. First, a questionnaire with 46 items was developed by interviewing patients with muscular dystrophies, amyotrophic lateral sclerosis, Morbus Pompe, neuropathies, and myasthenia gravis. Second, patients with proven neurological diseases answered the questionnaire. Third, a combination of classifiers (artificial neural network, support vector, and random forest) was trained and, finally, the system was challenged with new questionnaires. Users with an abnormal questionnaire pattern received a unique code for data privacy and contact details for a neurologist for further advice. The neurologists confirmed or refuted the AI-based diagnosis. The questionnaire was accessed 3122 times, leading to 853 unique codes. Only for a few patients the computer-based diagnoses and the confirmed final diagnoses were reported to us. However, for these few patients, the genetic testing and high CK levels finally ended their long-lasting diagnostic odyssey.

Multisubunit RNA polymerases (RNAP) carry out transcription in all domains of life; during vi-rus infection, RNAPs are targeted by transcription factors encoded by either the cell or the virus, resulting in the global repression of transcription with distinct outcomes for different host-virus combinations. These repressors serve as versatile molecular probes to study RNAP mechanisms, as well as they aid the exploration of druggable sites for the development of new antibiotics. Here, we review the mechanisms and structural basis of RNAP inhibition by the viral repressor RIP and the crenarchaeal negative regulator TFS4, which follow distinct strategies. RIP operates by occluding the DNA-binding channel and mimicking the initiation factor TFB/TFIIB. RIP binds tightly to the clamp and locks it into one fixed position, thereby preventing conformational oscil-lations that are critical for RNAP function as it progresses through the transcription cycle. TFS4 engages with RNAP in a similar manner to transcript cleavage factors such as TFS/TFIIS through the NTP-entry channel; TFS4 interferes with the trigger loop and bridge helix within the active site by occlusion and allosteric mechanisms, respectively. The conformational changes of RNAP described above are universally conserved and are also seen in inactive dimers of eukaryotic RNAPI and several inhibited RNAP complexes of both bacterial and eukaryotic RNA polymer-ases, including inactive states that precede transcription termination. A comparison of target sites and inhibitory mechanisms reveals that proteinaceous repressors and RNAP-specific antibiotics use surprisingly common ways to inhibit RNAP function.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

This scoping review investigated how consumers perceive and interpret serving size information on food packages. A search of seven databases (2010 to September 2017) was followed by title and abstract screening, with relevant articles assessed for eligibility in full-text. Fourteen studies met inclusion criteria, with relevant data extracted by one reviewer and checked for consistency by a second reviewer. Five studies reported poor understanding of nutrition facts labelling and portion size, with information to ‘benchmark’ serving size against reported as helpful in two studies. Consumer attitudes towards serving size labelling were measured in six studies and identified that serving size information was interpreted as indicative of nutrient intake regardless of portion size recommendations. Increased labelled serving sizes resulted in increased portion sizes in three studies, with three studies reporting the opposite or neutral effect for discretionary food portion sizes. The influence of labelled serving size on consumer attitudes and consumption is complex and sometimes counterintuitive. As labelled serving size can impact on consumption, any changes may result in unintended public health consequences. The effects of labelled serving size format changes should be tested carefully within experimental and ecological contexts and accompanied by tailored, comprehensive and serving size-specific food literacy initiatives.

University course scheduling (UCS) is one of the most important and time-consuming issues that all educational institutions face yearly. Most of the existing techniques to model and solve UCS problems have applied approximate methods, which are different in terms of efficiency, performance, and optimization speed. Accordingly, this research aims to apply an exact optimization method to provide an optimal solution to the course scheduling problem. In other words, in this research, an integer programming model is presented to solve the USC problem. In this model, hard and soft constraints include the facilities of classrooms, courses of different levels and compression of students' curriculum, courses outside the faculty and planning for them, and the limited time allocated to the professors. The objective is to maximize the weighted sum of allocating available times to professors based on their preferences in all periods. To evaluate the presented model's feasibility, it is implemented using the GAMS software. Finally, the presented model is solved in a larger dimension using a real data set from a college in China and compared with the current program in the same college. The obtained results show that considering the mathematical model's constraints and objective function, the faculty courses' timetable is reduced from 4 days a week to 3 working days. Moreover, master courses are planned in two days, and the courses in the educational groups do not interfere with each other. Furthermore, by implementing the proposed model for the real case study, the maximum teaching hours of the professors are significantly reduced. The results demonstrate the efficiency of the proposed model and solution method in terms of optimization speed and solution accuracy.

Collecting and recording physiological parameters and forwarding this data via telemedicine or remote surveys may significantly increase the health and safety of people working under extreme environmental conditions, like firefighters, mountain rescuers, disaster control employees, military personnel, etc. First, ruggedized systems, as small, lightweight, and flexible as possible, are needed to optimize the goal of increasing occupational health and safety of persons at risk and maximizing their performance during missions. Previous systems could only record a very limited number of parameters, and a few could forward the data online to return information to the user. Therefore, in order to record several meaningful, valid, and reliable physiological parameters synchronized, an extension of existing systems is required. This review highlights this problem and gives an overview of the historical development. The actual status of the systems available was listed and described comparatively. In the end, a proven, promising, and innovative solution is presented that can solve the problem and allow people to work more safely in extreme environments, which may represent the future.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

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

Companies have been increasing the amount of data that they collect from their systems and processes, considering the decrease in the cost of memory and storage technologies in recent years. The emergence of technologies such as Big Data, Cloud Computing, E-Science, and the growing complexity of information systems made evident that traceability and provenance are promising approaches. Provenance has been successfully used in complex domains, like health sciences, chemical industries, and scientific computing, considering that these areas require a comprehensive semantic traceability mechanism. Based on these, we investigate the use of provenance in the context of Software Process (SP) and introduce a novel approach based on provenance concepts to model and represent SP data. It addresses SP provenance data capturing, storing, new information inferencing and visualization. The main contribution of our approach is PROV-SwProcess, a provenance model to deal with the specificities of SP and its ability in supporting process managers to deal with vast amounts of execution data during the process analysis and data-driven decision-making. A set of analysis possibilities were derived from this model, using SP goals and questions. A case study was conducted in collaboration with a software development company to instantiate the PROV-SwProcess model (using the proposed approach) with real-word process data. This study showed that 87.5% of the analysis possibilities using real data was correct and can assist in decision-making, while 62.5% of them are not possible to be performed by the process manager using his currently dashboard or process management tool.

The global carbon neutrality challenge places a spotlight on forests as carbon sinks. However, greenhouse gas (GHG) balances of wood for material and energy use often reveal GHG emission savings in comparison with a non-wood reference. Is it thus better to increase wood production and use, or to conserve and expand the carbon stock in forests? GHG balances of wood products mostly ignore the dynamics of carbon storage in forests, which can be expressed as the carbon storage balance in forests (CSBF). For Germany, a CSBF of 0.25 to 1.15 t CO2/m³ wood can be assumed. When the CSBF is integrated into the GHG balance, GHG mitigation substantially deteriorates and wood products may even turn into a GHG source, e.g. in the case of energy wood. Here, building up the forest carbon sink would be the better option. We conclude that it is vital to include the CSBF in GHG balances of wood products if the wood is extracted from forests. Only then can GHG balances provide political decision-makers and stakeholders in the wood sector with a complete picture of GHG emissions.

A bottom-up route towards predicting evolution relies on deep understanding of the complex network proteins form inside cells. In a rapidly expanding panorama of experimental possibilities, the most difficult question is how to conceptually approach the disentangling of such complex networks. These can exhibit varying degrees of hierarchy and modularity, which obfuscate certain protein functions that may prove pivotal for adaptation. Using the well-established polarity network in budding yeast as a case study, we first organize current literature to highlight protein entrenchments inside polarity. Following three examples, we see how alternating between experimental novelties and subsequent emerging design strategies can construct a layered understanding, potent enough to reveal evolutionary targets. We show that if you want to understand a cell’s evolutionary capacity, such as possible future evolutionary paths, seemingly unimportant proteins need to be mapped and studied. Finally, we generalize this research structure to be applicable to other systems of interest.

In recent years, the management of health systems is a main concern of governments and decision makers. Home health care is one of the newest methods of providing services to patients in developed societies that can respond to the individual lifestyle of modern age and the increase of life expectancy. The home health care routing and scheduling problem is a generalized version of the vehicle routing problem, which is extended to a complex problem by adding special features and constraints of health care problems. In this problem, there are multiple stakeholders such as nurses for which an increase of their satisfaction level is very important. In this study, a mathematical model is developed to expand traditional home health care routing and scheduling models to downgrading cost aspects by adding the objective of minimizing the difference between the actual and potential skills of the nurses. Downgrading can lead to a dissatisfaction of the nurses. In addition, skillful nurses have higher salaries and high-level services increase equipment costs and need more expensive trainings and nursing certificates. Therefore, downgrading can enforce hidden huge costs to the managers of a company. To solve the bi-objective model, an -constraint based approach is suggested and the model applicability and its ability to solve the problem in various sizes are discussed. A sensitivity analysis on the Epsilon parameter is conducted to analyze the effect of this parameter on the problem. Finally, some managerial insights are presented to help the managers in this field, and some directions for future studies are mentioned as well.

The Food Boost Challenge (FBC) was developed using a participatory action research approach to enhance healthy eating behaviors, here vegetable and fruit products (V&amp;F-products) among adolescents, particularly those with lower education levels. FBC is a quadruple helix innovation process, involving adolescents, (peer)researchers, and food system partners of non-governmental and commercial organizations. In 2021-2022, 34 partners provided both cash and in-kind contributions to join the FBC-community. Phase 1 involved 200 students identifying barriers and drivers for consumption of F&amp;V-products among 1000 pre-vocational adolescents, aged 12-20 years. In phase 2, student teams submitted innovative ideas, resulting in 25 concepts fitting into ≥1 of 4 routes: I) innovative technology for a healthy diet, II) new food products/concepts for adolescents, III) hotspots improving F&amp;V-product experience, and IV) new routes to market. In phase 3 consortia of adolescents, students and partners were formed to develop 10 selected concepts into prototypes, and phase 4 offered teams a national platform. Results show FBC resonates with all stakeholders, generating valuable insights to increase F&amp;V-intake. Prototypes in all 4 routes have been developed, with some already in the implementation stage. Additionally, other regions in the Netherlands have adopted the FBC approach. Overall, FBC is an approach that transforms ideas into actionable measures and shows potential to be adapted to promote various healthy eating behaviors among school students.

In the context of Covid-19 virus containment, there is a lack of acceptance of preventive measures in the population. The present work investigated which factors influence the belief in of scientific propositions compared belief in conspiracy theories. The focus here was on the determinants of conspiracy beliefs in the context of Covid-19 related media content. Using an online questionnaire (N = 175), results indicate that scientific compared to conspiracy theoretical media content led to higher acceptance. Furthermore, Need for Cognition (NFC-K), a conspiracy theoretical worldview (CMQ), and openness to experience (NEO-FFI) were positively associated with conspiracy beliefs derived from Facebook postings. In addition, a conspiracy theoretical worldview was negatively associated with belief in scientific media content. Furthermore, agreeableness was unrelated to conspiracy beliefs, although it was positively associated with conspiracy theoretical worldview. The results imply promising persuasion strategies for reducing conspiracy theoretical beliefs and to increase the acceptance of preventive measures.

Three new species of genus Caridina are described from the northernmost part of Australia. Caridina darwin n. sp. resembles Caridina temasek Choy & Ng, 1991 from Singapore but differs in the armature of the rostrum, development of epipods on pereiopods and in lacking an appendix interna on male´s first pleopods. Caridina magnovis n. sp. resembles Caridina serratirostris de Man, 1892 but differs from this species in the armature of the ventral margin of the rostrum, a shorter stylocerite, a stouter carpus of first pereiopod, number and size of spiniform setae on third and fifth pereiopods, the shape of the preanal carina and in egg size. Caridina wilsoni n. sp. resembles Caridina gracilirostris de Man, 1892 but differs in egg size and some length to wide ratio of segments of the pereiopods. Detailed morphological descriptions of all three new species are given. A molecular phylogeny (mt DNA 16S) supports the morphospecies hypotheses and illustrates the phylogenetic relationship with morphologically similar species from outside Australia.

The use of visual signals in horticulture has attracted significant attention and encompassed a wide range of data types such as 2D images, videos, hyperspectral images, and 3D point clouds. These visual signals have proven to be valuable in developing cutting-edge computer vision systems for various applications in horticulture, enabling plant growth monitoring, pest and disease detection, quality and yield estimation, and automated harvesting. However, unlike other sectors, developing deep learning computer vision systems for horticulture encounters unique challenges due to the limited availability of high-quality training and evaluation datasets necessary for deep learning models. This paper investigates the current status of vision systems and available data in order to identify the high-quality data requirements specific to horticultural applications. We analyse the impact of the quality of visual signals on the information content and features that can be extracted from these signals. To address the identified data quality requirements, we explore the usage of a deep learning-based super-resolution model for generative quality enhancement of visual signals. Furthermore, we discuss how these can be applied to meet the growing requirements around data quality for learning-based vision systems. We also present a detailed analysis of the competitive quality generated by the proposed solution compared to cost-intensive hardware-based alternatives. This work aims to guide the development of efficient computer vision models in horticulture by overcoming existing data challenges and paving a pathway forward for contemporary data acquisition.

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

Phosphorus (P) is the most important substance in inorganic fertilizers used in agriculture industry. In this study, a multi-product and multi-objective model is presented considering economic and environmental concerns to design a renewable and sustainable P-fertilizer supply chain management (PFSCM). To handle complexities of the proposed model, an ensemble knowledge-based three-stage heuristic-metaheuristic algorithm utilizing heuristic information available in the model, whale optimization algorithm, and variable neighborhood search (named H-WOA-VNS) is proposed. At first, a problem-dependent heuristic is designed to generate a set of near-optimal feasible solutions. These solutions are fed into a population-based whale optimization algorithm which benefits from both exploration and exploitation strategies. Finally, a single-solution metaheuristic based on variable neighborhood search is applied to further improve the quality of the solution using local search operators. The objective function of the algorithm is formulated as a weighted average function to minimize total economic cost, while increasing crop yield and P use efficiency. Experimental results over five synthetic datasets and a real case study of the P-fertilizer supply chain confirm the superiority of the proposed method against the state-of-the-art techniques. The results demonstrate that the proposed method performs well in optimizing both the economic cost and environmental issues.

: Schizophrenia and schizoaffective disorder are generally treated with second-generation antipsychotic drugs. These drugs are mostly D2 and 5-HT2A antagonists. They improve positive schizophrenia symptoms sufficiently well; however, they ameliorate negative schizophrenia symptoms and cognitive functions to a small extent. We review novel antipsychotic drugs exerting a partial agonism at dopaminergic and serotonergic receptors such as cariprazine, brexipiprazole and lumateperone. Besides, the mechanisms of actions of non-anti-dopaminergic antipsychotic drugs are pointed out. Updated neural networks are used to explain the mechanism of action of M4 and M1 receptor agonists, for example xanomeline combined with trospium or emraclidine, and trace-amine-associated receptor 1 agonists (TAAR1), for example ulataront. Phase 3 clinical trials of new third generation antipsychotic drugs are presented. Novel antipsychotic drugs with a partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms as well as cognitive symptoms better than second generation antipsychotic drugs. Besides, they are well tolerated. M4 and M1 receptor agonists, i.e. xanomeline combined with trospium or emraclidine, and TAAR1 agonists, i.e. ulataront, have promising results in clinical trials; they well improve negative schizophrenia symptoms and cognitive functions. Phase 3 clinical trials offer promising results for anti-dopaminergic and non-anti-dopaminergic novel antipsychotic drugs. These new non-anti-dopaminergic antipsychotic drugs better emend negative schizophrenia symptoms, and they better improve cognitive functions than second-generation antipsychotic drugs. Promising new antipsychotic drugs are cariprazine, brexipiprazole, lumateperone, ulataront, and xanomeline combined with trospium. Although phase 3 clinical studies are not yet completed, they showed a therapeutic effect superior to those achieved by second-generation antipsychotic drugs. They are tolerated very well, and they better treat negative schizophrenia symptoms and improve cognitive functions.

Heart disease is a global health concern of paramount importance, causing a significant number of fatalities and disabilities. Precise and timely diagnosis of heart disease is pivotal in pre-venting adverse outcomes and improving patient well-being, thereby creating a growing demand for intelligent approaches to predict heart disease effectively. This paper introduces an Ensemble Heuristic-Metaheuristic Feature Fusion Learning (EHMFFL) algorithm for heart disease diagnosis. Within the EHMFFL algorithm, a diverse ensemble learning model is crafted, featuring different feature subsets for each heterogeneous base learner, including support vector machine, K-nearest neighbors, logistic regression, random forest, naive bayes, decision tree, and XGBoost. The primary objective is to identify the most pertinent features for each base learner, leveraging a combined heuristic-metaheuristic approach that integrates the heuristic knowledge of Pearson correlation coefficient with the metaheuristic-driven grey wolf optimizer. The second objective is to aggregate the decision outcomes of the various base learners through ensemble learning, aimed at constructing a robust prediction model. The performance of the EHMFFL algorithm is rigorously assessed using the Cleveland and Statlog datasets yielding remarkable results with an accuracy of 91.8% and 88.9%, respectively, surpassing state-of-the-art machine learning, ensemble learning, and feature selection techniques in heart disease diagnosis. These findings underscore the potential of the EHMFFL algorithm in enhancing diagnostic accuracy for heart disease and providing valuable support to clinicians in making more informed decisions regarding patient care.

Most of the commonly used Ionic Liquids (ILs) contain bulky organic cations with suitable anions. With our COMPLET (Concept of Melting Point Lowering due to Ethoxylation), we follow a different approach. We use simple, low-toxic, cheap and commercially available anions of the type Cx(EO)yCH2COO– to liquefy presumably any simple metal ion, independently of its charge. In the simplest case, the cation can be sodium or lithium, but synthesis of Ionic Liquids is also possible with cations of higher valences such as transition or rare earth metals. Anions with longer alkyl chains are surface active and form surface active ionic liquids (SAILs), which combine properties of ionic and nonionic surfactants at room temperature. They show significant structuring even in their pure state, i.e. in the absence of water or any other added solvent.

The complex color patterns on the wings and body of Drosophila guttifera (D. guttifera) are emerging as model systems for studying evolutionary and developmental processes. Studies regarding these processes depend on overexpression and down-regulation of developmental genes, which ultimately rely upon an effective transgenic system. Methods describing transgenesis in Drosophila melanogaster (D. melanogaster) have been extensively reported in several studies. However, these methods cannot be directly applied to D. guttifera due to the low egg production rate and very delicate embryos’ pre-injection treatment requirements. In this protocol, we describe extensively a comprehensive method used for generating transgenic D. guttifera. Using the protocol described here, we are able to establish transgenic lines, identifiable by the expression of Enhanced Green Fluorescent Protein (EGFP) in the eye disks of D. guttifera larvae. The entire procedure, from injection to screening for transgenic larvae, can be completed in approximately 30 days and should be relatively easy to adapt to other non-model Drosophila species, for which no white-eyed mutants exist.

Methods based on simulation pedagogy are widely used to practice hands on skills in safety environment. The usability of an EEG-simulator on clinical neurophysiology course was evaluated. Second year biomedical laboratory science students (N=35) on this course was included in the study. They were divided into three groups. Two groups used the EEG simulator with different feedback modes and one group without use of the simulator. Results was expected to reveal a correlation between user experience and learning outcomes. This study made used of a mixed method study design. During the study students were asked to keep a learning diary throughout the course on their experience. Diaries were analyzed qualitatively based on content analyses. Quantitative analyses based on an UX questionnaire that measures classical usability aspects (efficiency, perspicuity, dependability) and user experience aspects (novelty, stimulation) and the students’ feelings to use simulator. The quantitative data was analyzed using SPSSTM software. The quantitative and qualitative analyses showed that the use of EEG-simulator which was evaluating teaching-learning process have an extra benefit in clinical neurophysiology education and students felt that simulator is useful in learning. The simulation debriefing session should be followed by a full theoretical and practical session. Students compare their learning from the simulator with that of the actual placement which fosters the reflective practice of learning again deepening the understanding of the EEG electrode placement and different wave patterns.

Quantum image representation is a widely researched area of quantum computing. Currently developed methods use angle parameter of the rotation gate (e.g., the FRQI method), sequences of qubits (ex. NEQR method) or phase shift (ex. LPIQE method) for storing color information of pixels. All of those methods are affected by decoherence and other classical and quantum noise, which is an inseparable part of quantum computing in a NISQ (Noisy Intermediate Scale Quantum) era. These all phenomenons influence the measurements, its probability distribution over the measurement basis and, as the result, makes the extracted images not even similar to those, which was stored in quantum computers. Since this process is, in its foundation, quantum as well, the computational reversal of this process is possible. There are a lot of methods for error correction, mitigation and reduction, but all of them use quantum computer time, or additional qubits to achieve desired result. We report a successful use of the Generative Adversarial Network tuned for image-to-image translation in conjunction with PDU method, for error reduction in images encoded using LIPQE (Local Phase Image Quantum Encoding) method.

Social networks are experiencing great popularity, with Instagram currently being the most intensively used network. On these platforms, users are continuously exposed to self-relevant information that fosters social comparisons. A distinction is made between ability-based and opinion-based comparison dimensions. To experimentally investigate the influence of these comparison dimensions on users' subjective well-being, an online exposition experiment (N = 409) was conducted. In a preliminary study (N = 107), adequate exposition stimulus material was selected in advance. The results of the main study indicated that exposition of ability-related social comparisons in the context of social media elicited lower well-being than exposition of opinion-related social comparisons. Theoretical and practical implications of the findings were discussed and suggestions for future work were outlined.

Symbolic pole/zero analysis is an important step when designing an analog operational amplifier. Generally, a simplified symbolic analysis of analog circuits suffers from NP-hardness, i.e., an exponential growth of the number of symbolic terms of the transfer function with the circuit size. In this study, we present a mathematical model combined with a heuristic-metaheuristic solution method for the symbolic pole/zero simplification in operational transconductance amplifiers (OTA). At first, the circuit is symbolically solved and an improved root splitting method is applied to extract symbolic poles/zeroes from the exact expanded transfer function. Then, a hybrid algorithm based on heuristic information and a metaheuristic technique using simulated annealing is performed for the simplification of the derived symbolic pole/zero expressions. The developed method has been tested on three analog OTAs. The obtained results show the effectiveness of the proposed method to achieve accurate simplified symbolic pole/zero expressions with the least complexity.

Left ventricular (LV) longitudinal function is mechanically coupled to the elasticity of the ascending aorta (AA). The pathophysiologic link between stiff AA and reduced longitudinal strain and subsequent deterioration in longitudinal LV systolic function is likely relevant in heart failure with preserved ejection fraction (HFpEF). A proposed therapeutic effect of freeing the LV apex and allowing for LV inverse longitudinal shortening was studied in-silico utilizing Living Left Heart Human Model (Dassault Systémes Simulia Corporation). LV function was evaluated in a model with A) Elastic AA; B) Stiff AA; and C) Stiff AA with free LV apex. The cardiac model simulation demonstrated that freeing the apex caused inverse LV longitudinal shortening that can abolish the deleterious mechanical effect of a stiff AA on LV function. A stiff AA and impairment of LV longitudinal strain are common in patients HFpEF. The hypothesis-generating model strongly suggests that freeing the apex and inverse longitudinal shortening may improve LV function in HFpEF patients with a stiff AA.

Development of accelerometer-based lameness (mobility) detection has focused on cow behaviors such as lying and walking. Several studies, usually small, have reported levels of accuracy up to 91%. However, there has been limited independent replication of these results. In this study, behavior measures previously identified as being associated with lameness such as lying bouts and walking time are examined in relation to mobility score. On a research farm and a commercial farm, four trials were completed with 65 grazing cows. The cows had differing mobility scores ranging from perfect mobility to impaired mobility. Behavior was monitored using leg worn accelerometers. In general, behavior and mobility associations identified in previous studies were not found. Behavior monitoring with accelerometers as a basis to classify impaired mobility in pasture-based contexts thus remains challenging.

Biological nitrogen fixation (BNF) by symbiotic bacteria plays a vital role in sustainable agriculture. However, current quantification methods are often expensive and impractical. This study explores the potential of Raman spectroscopy, a non-invasive technique, for rapid assessment of BNF activity in soybeans. Raman spectra were obtained from soybean plants grown with and without rhizobia bacteria to identify spectral signatures associated with BNF. δN15 isotope ratio mass spectrometry (IRMS) was used to determine actual BNF percentages. Partial least squares regression (PLSR) was employed to develop a model for BNF quantification based on Raman spectra. The model explained 80% of the variation in BNF activity. To enhance the model's specificity for BNF detection regardless of nitrogen availability, a subsequent elastic net (Enet) regularization strategy was implemented. This approach provided insights into key wavenumbers and biochemicals associated with BNF in soybeans.

During the COVID-19 pandemic face masks grew in importance as their use by the general population was recommended by health officials in order to minimize the risk of infection and prevent further spread of the virus. To ensure health protection of medical personal and other system relevant staff, it is of considerable interest to quickly test if a certain lot of filtering facepiece masks meets the requirements or if the permeability changes under different conditions. As certified penetrometers are rather expensive and were difficult to obtain during the COVID-19 pandemic, we describe two quite simple and cheap methods to quickly test the filter permeability based on an electronic cigarette. The first method uses a precision scale, the second method uses a light scattering detector to measure the filter penetration. To make sure these two methods yield reliable results, both were tested with freshly cut filter samples covering the range of approx. 7% to 60% permeability and compared to the results of a certified penetrometer. The comparison of the two methods with the certified penetrometer showed a good correlation and therefore allow a quick and rather reliable estimation of the permeability. Several examples about the use of faulty masks and the resulting health risks show that simple, fast, cheap and broadly available methods for filter characterization might be useful in these days.

The Swiss Personalized Health Network (SPHN) is a Swiss research infrastructure initiative that aims to facilitate the exchange of health-related data in a FAIR manner. The SPHN Dataset and SPHN RDF Schema form an essential part of the SPHN Semantic Interoperability Framework, which currently covers mostly clinical routine data. To facilitate the integration of omics data produced by the SPHN National Data Streams, a genomics extension was developed. This was done in close collaboration with clinicians, researchers, bioinformaticians, and data managers, from Swiss university hospitals, academic research groups and the omics platforms. Here, we present the genomics extension of the SPHN RDF Schema, which can be used to semantically describe genomics experiments and covers both clinical and research domains. The schema centers around the general omics process flow, with concepts that denote the individual steps, such as sample processing, assay, and data processing. Genomics-specific specializations are provided, such as library preparation, sequencing assay, and sequencing analysis. The schema also facilitates in capturing other important omics metadata, such as information about the sequencing instrument, standard operating procedure, and quality control metrics. The extension aligns with existing semantic data models and reuses common biomedical vocabularies, such as EDAM, OBI and FAIR genomes, as value sets, thereby facilitating semantic interoperability. It will be used to FAIRify data that is produced within the Swiss network and to facilitate sharing this data as one knowledge graph for reuse among its participants.

Distribution System Operators (DSOs) are adapting to changing energy demands and the shift toward renewable and decentralized energy. Circularity is increasingly relevant for DSOs as their distribution systems age and need replacing. Taking circular action, however, is generally regarded as challenging as the current circular economy (CE) landscape is highly fragmented and rarely touches the implementation level. A longitudinal case study at Dutch DSO Liander on the circu-larity of distribution transformers was used to understand empirical success factors for taking circular action and to generate prescriptive knowledge on the operationalization of circularity. Six design propositions for circular action were formulated that suggest to 1) initiate small-scale cir-cularity experiments, 2) involve technical and strategic experts, 3) synergize circularity with more urgent, primary goals 4) translate circular initiatives bottom-up and top-down, 5) collaborate with other DSOs, and 6) create multidisciplinary teams. At DSO Liander, selecting the right interventions depending on the changing context contributed to operationalizing circularity for distribution transformers and achieving circularity targets. The generalizable design propositions could assist other DSOs in optimizing their strategy toward circular action.

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

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

Already more than 140 countries consider or have pledged to reach net-zero emission targets by 2050 or earlier and the share of global emissions falling into an emission pricing scheme has steeply increased over the past three years. Even where there are no direct implications for industry (yet), there is a series of subtle pressure points driving an increasing number of companies across the globe to work towards climate neutrality and pledging ambitious emission reduction goals. This article sheds light on the pressure points, the subtle triggers, the underlying considerations as well as the hoped-for benefits for industrial companies from achieving net-zero emissions. The observations and ideas presented in this paper are derived from quantitative data obtained via the Energy Efficiency Index of German Industry (EEI) and qualitative data. Not only societal, work force, supply chain and investor expectations play a large role, but also many strategic considerations which have the potential to make the company more resilient and profitable, particularly in time of crisis. Those companies that do not move towards decarbonisation, on the other hand, may face a costly late-mover disadvantage. This piece uncovers subtle interconnections, helping stakeholders from industry and beyond to grasp opportunities and challenges ahead.

Far too often, one meets patients who went for years or even decades from doctor to doctor, without getting a valid diagnosis. This brings pain to millions of patients and their families, not to speak of the enormous costs. Often patients cannot tell precisely enough which factors (or combinations thereof) trigger their problems. If conventional methods fail, we propose the use of statistics and algebra to give doctors much more useful inputs from patients. We use statistical regression for independent triggering factors for medical problems, and “balanced incomplete block designs” for non-independent factors. These methods can supply doctors with much more valuable inputs, and can also detect combinations of multiple factors by incredibly few tests. In order to show that these methods do work, we briefly describe a case in which these methods helped to solve a 60 year old problem in a patient, and give some more examples where these methods might be very useful. As a conclusion, while regression is used in clinical medicine, it seems to be widely unknown in diagnosing. Statistics and algebra can save the health systems much money, and the patients also a lot of pain.

One of the challenges facing the industrial adoption of additively manufactured parts is the surface roughness on the as-built part. The surface roughness of parts is frequently characterized by metrics specified by international standards organizations. However, these standards list many surface metrics that can make it unclear which to use to best describe the surface. In this work, the ability of the various surface metrics to successfully classify the as-built and post-processed surfaces is studied using linear classification models. Laser polishing via remelting and manual grinding are the post-processing techniques used to smooth the as-built surface. The ability of the linear classifier to successfully categorize the various surfaces is demonstrated, and the various surface metrics are ranked according to the strength of their individual ability to classify the surfaces. This work promotes the method as a potential way to autonomously classify as-built and laser polished surfaces.

Economic risks for livestock production are caused by volatile commodities and market conditions, but also by environmental drivers like increasing uncertainties due to weather anomalies and global warming. These risks impact the gross margin of farmers and can stimulated investment decisions. For confined pig and poultry production, farmers can reduce the environmental impact by implementing specific adaptation measures to reduce heat stress. A simulation model driven by meteorological data was used to calculate heat stress impact as a projection for 2030. For a business-as-usual livestock building, the indoor climate for several adaptation measures was calculated. The weather-related value-at risk quantified the economic risks caused by global warming and the stochastic component of the weather. The results show that only energy-saving adaptation measures to reduce the inlet air temperature are appropriate to reduce the economic risk to the level of the year 1980. The efficiency of other adaptation measures to reduce heat stress is distinctly lower. The results in this study can support the decision making of farmers concerning adaptation management and investments. It can inform agricultural policy design as well as technological development.

In the last decades farm animals kept in confined and mechanically ventilated livestock buildings are increasingly confronted with heat stress (HS) due to global warming. These adverse conditions cause a depression of animal health and welfare and a reduction of the performance up to an increase of the mortality. To facilitate sound management decisions, livestock farmers need relevant arguments, which quantify the expected economic risk and the corresponding uncertainty. The economic risk was determined for the pig fattening sector based on the probability of HS and the calculated decrease in the gross margin. The model calculation for confined livestock buildings showed, that HS indices calculated by easily available meteorological parameters can be used for assessment quantification of indoor HS, which is so far difficult to determine. These weather-related HS indices can be applied not only for an economic risk assessment but also for a weather-index based insurance for livestock farms. Based on the temporal trend between 1981 and 2017, a simple model was derived to assess the likelihood of HS for 2020 and 2030. Due to global warming, the return period for a 90-percentile HS index is reduced from 10 years in 2020 to 3-4 years in 2030. The economic impact of HS on livestock farms was calculated by the relationship between an HS index based on the temperature-humidity index (THI) and the reduction of the gross margin. From the likelihood of the HS and this economic impact function, the probability of the economic risk could be determined. The reduction of the gross margin for a 10 year return period was determined for 1980 with 0.27 € per year and animal place and increased by the 20-fold to 5.13 € per year and animal place in 2030.

Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of Staphylococcus aureus protein A (PA) on every coat protein (CP) subunit (TVCVPA) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCVPA and the wildtype subgroup 3 tobamovirus. TVCVPA could be loaded with more than 500 IgGs per virion, which mediated the immunocapture of fluorescent dyes, GFP and active enzymes. Bi-enzyme ensembles of cooperating glucose oxidase and horseradish peroxidase were tethered together on the TVCVPA carriers by a single antibody type, with one enzyme conjugated chemically to its Fc region, and the other one bound as target, yielding synthetic multienzyme-complexes. In microtiter plates, the TVCVPA-displayed sugar-sensing system possessed a considerably increased reusability upon repeated testing, compared to the IgG-bound enzyme pair in the absence of the virus. A high coverage of the viral adapters was achieved also on Ta2O5 sensor chip surfaces coated with a polyelectrolyte interlayer, as a prerequisite for durable, TVCVPA-assisted electrochemical biosensing through modularly IgG-assembled sensor enzymes.

Fossil-based emissions can be avoided through using wood in place of non-renewable raw materials as energy and materials. However, increasing wood harvest influences forest carbon stocks. This effect may reduce the overall climate benefit of wood use significantly but is widely overlooked. We carried out a systematic review of simulation studies and compared differences in forest carbon and amount of wood harvested between more and less intensive wood harvest scenarios for three different time perspectives; short (1-30 years), mid (31-70 years) and long (71-100 years). Out of more than 450 reviewed studies 44 provided adequate data. Our results show that increased harvesting reduced carbon stocks over 100 years in temperate and boreal forests roughly 1.6 (stdev 0.9) t_C per t_C harvested. The value proved to be robust when outliers explicitly influenced by other factors than change in harvest rate, such as increase in fertilization or forest area, were removed. Interestingly, no significant difference in carbon impacts was found for average values of boreal and temperate forests or between short and long time-horizons. However, impacts tend to be greatest in the mid-term. This carbon balance indicator that we estimated can be interpreted as carbon debit of wood harvest in forests. It is significant compared with the typical GHG credits in technosphere generated by avoiding fossil emissions in substitution and increase in carbon storage in harvested wood products, and should not be ignored. Our estimates provide default values that can directly be included in GHG balances of products or assessment of mitigation policies and measures related to wood use. However, more systematic scenarios and transparent data in which different factors influencing forest carbon stocks are separately studied are clearly required to provide better constrained estimates for specific forest types.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the development of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs.; (2) Methods: Single-center retrospective study in patients with ADRs post-mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines).; (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculo-papular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular lympho-histiocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred post-second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% and maculo-papular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients.; (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. The majority of ADRs are self-limited with a few extending beyond a month.

In Switzerland, psychomotor therapy (PMT) is a standard treatment for children with graphomotor impairments, but scientific evidence of its effectiveness is rare. To investigate the effectiveness of PMT, we conducted a randomized field trial (RFT). The sample consisted of 121 first and second graders with graphomotor impairments, some of whom met the criteria of developmental coordination disorder, while the remaining suffered from developmental dysgraphia. The treatments lasted over 5 months. Handwriting fluency and consistency were measured five times on a digitizing tablet. All participating children completed a self-concept interview, and a standardized fine motor performance test twice. Psychomotor therapy significantly improved the fine motor skills of the therapy group compared to those of the waiting group. However, there was no evidence that the treated children improved more than the waiting children in terms of their graphomotor skills such as frequency, automaticity, and consistency of forming letters. Finally, the children of the therapy group showed partial improvements in their handwriting self-concept, while those of the waiting group children remained stable. This short-term RFT demonstrated the effectiveness of PMT in terms of fine motor skills and some aspects of the handwriting self-concept but showed no effects on handwriting fluency and consistency.

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, affecting between 0.7% and 1% of all live births. Approximately 11% of infected newborns are symptomatic at birth, and between 30% and 40% of these are at risk of developing long-term neurological sequelae. Until recently, the lack of an effective treatment did not justify universal testing of pregnant women. In recent years, however, valacyclovir at a dose of 8 g/day has been shown to be effective in preventing vertical transmission, and ganciclovir has been shown to be effective in preventing long-term sequelae in the treatment of symptomatic neonates. The aim of this article is to review congenital CMV infection, from its epidemiology to its treatment, using the most recent studies in the literature, and to help in the decision to modify protocols for universal testing of pregnant women according to the possibilities of each locality.

Among others, UWB-based multi anchor localization systems have been established for industrial indoor localization systems. However, multi anchor systems have high costs and installation effort. By exploiting the multipath propagation of the UWB signal, the infrastructure and thus the costs of conventional systems can be reduced. Our UWB Single Anchor Localization System (SALOS) successfully pursues this approach. The idea behind SALOS is to create a localization system with a sophisticated signal modeling. Therefore, neither measured reference like fingerprinting nor training is required for position estimation. Although SALOS has been implemented and tested successfully already in an outdoor scenario with multipath propagation, it has not yet been evaluated in indoor environment with challenging and hardly predictable multipath propagation. For this purpose, we have developed new algorithms for the existing hardware mainly a three-dimensional statistical multipath propagation model for arbitrary spatial geometries. The signal propagation between the anchor and predefined candidate points for the tag position is modeled in path length and complex-valued receive amplitudes. For position estimation, these modeled signals are combined to multiple sets and compared to UWB measurements via a similarity metric. In the end, a majority decision of multiple position estimates is performed. For evaluation, we implement SALOS in a modular fashion and install the system in a building. For a fixed grid of 20 positions, SALOS is evaluated in terms of position accuracy. The system results in correct position estimations for more than 73% of the measurements.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

How complex morphological patterns form is an intriguing question in developmental biology. However, the mechanisms that generate complex patterns remain largely unknown. Here we sought to identify the genetic mechanisms that regulate the tan (t) gene in a multi-spotted pigmentation pattern on the abdomen and wings of Drosophila guttifera. Previously, we showed that yellow (y) gene expression completely prefigures the abdominal [1] and wing [2] pigment patterns of this species. In the current study, we demonstrate that the t gene is co-expressed with the y gene in nearly identical patterns, both transcripts foreshadowing the adult abdominal and wing melanin spot patterns. We identified cis-regulatory modules (CRMs) of t, one of which drives reporter expression in six longitudinal rows of spots on the developing pupal abdomen, while the second CRM activates the reporter gene in a spotted wing pattern. Comparing the abdominal spot CRMs of y and t, we found a similar composition of putative transcription factor binding sites that are thought to regulate the complex expression patterns of both terminal pigmentation genes y and t. In contrast, the y and t wing spots appear to be regulated by distinct upstream factors. Our results suggest that the D. guttifera abdominal and wing melanin spot patterns have been established through the co-regulation of y and t, shedding light on how complex morphological traits may be regulated through the parallel coordination of downstream target genes.

Spatial and temporal variation of the free electron concentration in the ionosphere affects SAR interferograms, in particular at low radar frequencies. In this work the identification, estimation and compensation of ionospheric path delay phases in PALSAR-3 and NISAR-L interferograms is discussed. Both these L-band sensors acquire simultaneously SAR data in a main spectral band and in an additional, spectrally separated, narrower second band to support the mitigation of ionospheric path delays. The methods presented permit separating the dispersive and the non-dispersive phase terms based on the double-difference interferogram between the two available spectral bands and the differential interferogram of the main band. The applicability of the proposed methods is demonstrated using PALSAR-3-like data that was simulated based on PALSAR-2 SM1 mode data.

The theory of heavy ion double charge exchange (DCE) reactions proceeding by effective rank–2 isotensor interactions is presented. Virtual pion–nucleon charge exchange interactions are investigated as the source for induced isotensor interactions, giving rise to the Majorana DCE (MDCE) reaction mechanism. MDCE is of a generic character, proceeding through pairs of complementary (π±,π∓) reactions in the projectile and target nucleus. The dynamics of the elementary processes is discussed where the excitation of pion–nucleon resonances are of central importance. Investigations of initial and final state ion–ion interactions show that these effects are acting as vertex renormalizations. In closure approximation, well justified by the finite pion mass, the second order transition matrix elements reduce to pion potentials and effective two–body isotensor DCE interactions, giving rise also to two–body correlations in either of the participating nuclei. Connections to neutrinoless Majorana double beta decay (MDBD) are elucidated at various levels of dynamics, from the underlying fundamental electro–weak and QCD scales to the physical scales of nuclear MDBD and MDCE physics. It is pointed out that heavy ion MDCE reactions may also proceed by competing electro–weak charge exchange processes, leading to lepton MDCE by electrons, positrons, and neutrinos.

Depressions containing partially molten rocks were investigated in Quaternary pebbly sedi-ments in Alpine foreland in Bavaria, Germany. Ruins of limekilns from 18-19th centuries are abundant around Seeshaupt. They are usually associated with earthworks for fuel feeding and protection from wind. Depressions contain partially molten stones from furnace walls, with lime and burnt loam remnants. On the surface of pebbles (typically gneisses), green glass formed with chemical composition possibly affected by moderately volatile components of wood biomass, mainly K and Cu. Thermoplastic deformation of pebbles is limited and the sur-face melt deformation points to slow flow. At Emmerting, on the other hand, two walled circu-lar depressions which lack additional earthworks have been identified as possible impact cra-ters. Thermally affected pebbles show much more intense deformation. Colorless to greenish glass, also K and Cu enriched, usually forms only thin surface coatings, in places covered by younger melt extruded from pebble interior. Burnt loam is missing. At Grabenstätt-Kaltenbach, a depression of unclear origin was investigated. Morphologically, it matches craters rather than limekilns, but anthropogenic contamination (brick-like material) is probable. The rare molten samples do not display extreme deformation features. The thermally affected stones, mainly those from Emmerting, have elevated magnetic susceptibility.

The quickest and easiest way to avoid greenhouse gas (GHG) emissions is to purchase renewable electricity and offset the remaining emissions. However, the industrial sector’s electricity needs already exceed renewable electricity generation. Moreover, electricity accounts for only one third of the industry’s energy needs. Simultaneously, the advance of sectoral coupling and the decarbonisation of industrial processes, as well as the desire to rapidly decrease dependence on fossil fuels, are creating significant additional demand for renewable energy. Neither existing nor planned generation and transmission infrastructure will suffice to meet the expected short-term demand. Based on survey data from the German Industry Energy Efficiency Index, this article therefore examines the share of GHG savings that companies intend to achieve on- and off-site. Understanding how much additional generation and transmission capacity is needed by the industry to decarbonise and by when is crucial to identify and address the extent of excess demand. On average, companies plan to avoid 22 % of their 2019 emissions by 2025 and 27 % by 2030, primarily through on-site measures. In combination with the extrapolation of the entire industry’s needs for off-site capacity, the data calls for a rapid expansion of planning authority and green generation capacities.

Purpose: The aim of the present experimental 3D-finite element study was to evaluate the influence of an augmented sinus lift with an additional inserted bone graft block. The bone graft block stabilizes the implant in addition to conventional augmented bone. We placed the block in three different positions. The implants were loaded with axial force and forces secondary to laterotrusion and protrusion. Material and Methods: A simplified U-shaped 3D finite element model of the upper jaw and a more complex anatomical model of the left maxilla were created. The bone graft block was placed in three positions: in the lower third in contact with the sinus floor, the middle, and the upper third of the implant. Van Mises’ stress distribution was calculated and analyzed for the different models. We also compared the complex anatomical model with the simplified one. Results: The position of the bone graft block significantly influences the magnitude of stress distribution. A bone graft block positioned in the upper third or middle of the implant reduces the quantity of stress compared to the reference model without a bone graft block. The low bone graft block position is clearly associated with lower stress distribution in compact bone. We registered no significant differences in stress in compact bone with regard to laterotrusion or protrusion. Conclusions: Maximum values of von Mises stresses in compact bone can be reduced significantly by using a bone graft block. The reduction of stress is nearly the same for positions in the upper third and the middle of the implant. It is much more pronounced when the bone graft block is in the lower third of the implant near the sinus floor, which appeared to be the best position in the present study.

Mastectomy and hysterectomy with bilateral salpingo-oophorectomy are the first steps in surgical female-to-male (FtM) gender affirmation. We aimed to critically review our experience with the combined approach of hysterectomy/salpingo-oophorectomy and bilateral mastectomy and to focus on intra- and postoperative complications. In a retrospective cohort study, 108 consecutive patients were included who underwent combined hysterectomy, bilateral salpingo-oophorectomy, and bilateral mastectomy in a single operating session, between November 1998 and December 2017. Main outcome measures were operating times and intra- and postoperative courses, including major and minor adverse events. Patients were 28.9 ± 6.7 years of age and revealed a mean BMI of 24.4 ± 4.1 kg/m2. The median total operating time for patients without additional procedures was 237.6 ± 110.3 minutes. Taking all intra- and postoperative complications together, there were eight (7.4%) and 21 (19.4%) patients with major and minor complications, respectively. The most frequent complication was breast hematoma (18/108, 16.7%). There was a completely uneventful intra- and postoperative course in 82 cases (75.9%). In conclusion, for FtM reassignment surgery, the combined hysterectomy / salpingo-oophorectomy and bilateral mastectomy in a single operating session seems to be feasible and safe.

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

From the perspective of manufacturing companies, the political, media and economic discourse on decarbonisation of the recent years manifests itself as an increasing social expectation of action. In Germany in particular, this discourse is also being driven forward by powerful companies, respectively sectors, most notably the automotive industry. Against this background, it was examined how German manufacturing companies react to rising societal pressure and emerging policies. It is examined which measures the companies have taken or plan to take to reduce their footprint, which aspirations are associated with this and by which structural characteristics (company size, energy intensity, sector) these are influenced. A mix methods approach was applied, utilising data gathered from approx. 900 companies in context of the Energy Efficiency Index of German Industry (EEI), along with media research focusing on decarbonisation plans and initiatives announced. We demonstrate that one-size-serves-all approaches are not suitable to decarbonise industry as the situation and ambitions differ considerably depending on size, energy intensity and sector. Even though the level of ambition and urgency is high, particularly micro and energy intensive companies are challenged. The research uncovers a series of questions that call for attention to materialise the ambitions and address the challenges outlined.

This contribution shows the possibilities of a low-cost multipurpose data logger that was built around an Arduino Mega 2560 single board computer. To transform the Arduino Mega into such a data logger, a sensor shield was designed that contains an SD-card, real-time clock, and different kinds of connectors so that sensors can easily be attached to the device. The software considers a wide range of predefined sensors from which a user can choose. To assess the performance of such a device, short-term monitoring campaigns in relation to outdoor air quality, human activity in an office, motion of a journey on a bike, and exhaust gas monitoring of a diesel generator were realized. Besides the possibilities to apply the data logger in different kinds of applications, a method is proposed to assess the credibility of such a system. The assessment based on the various short-term campaigns showed that the system scores positively on most of the performance indicators, but that unexpected (black swan) events affect the assessment over the longer term. This makes the development of low-cost scientific instruments harder than expected. The stability and long-term performance of this type of design requires continuous evaluation and engineering correction.

Magnetic force microscopy (MFM) is a widespread technique for imaging magnetic structures with a resolution of some 10 nanometers. MFM can be calibrated to obtain quantitative (qMFM) spatially resolved magnetization data in units of A/m by determining the calibrated point spread function of the instrument, its instrument calibration function (ICF), from a measurement of a well-known reference sample. Beyond quantifying the MFM data, a deconvolution of the MFM image data with the ICF also corrects the smearing caused by the finite width of the MFM tip stray field distribution. However, the quality of the calibration depends critically on the calculability of the magnetization distribution of the reference sample. Here, we discuss a Ti/Pt/Co multilayer stack which shows a stripe domain pattern as a suitable reference material. A precise control of the fabrication process combined with a characterization of the sample micromagnetic parameters allows to reliably calculate the sample’s magnetic stray field, proven by a very good agreement between micromagnetic simulations and qMFM measurements. A calibrated qMFM measurement using the Ti/Pt/Co stack as a reference sample is shown and validated and the application area for quantitative MFM measurements calibrated with the Ti/Pt/Co stack is discussed.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and significant structural differences of its glycolytic enzymes compared to their human counterpart, glycolysis is considered as a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK), containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion which lines the active site. Moreover, we propose that this insertion plays a role upon ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both Sglutathionylation and Snitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.

During the last years some new variants of Permutation entropy have been introduced and applied to EEG analysis, among them a conditional variant and variants using some additional metric information or being based on entropies different from the Shannon entropy. In some situations it is not completely clear what kind of information the new measures and their algorithmic implementations provide. We discuss the new developments and illustrate them for EEG data.

Introduction.Sars-CoV-2 infection poses particular problems in pregnancy, as the infection more frequently causes severe complications than in unaffected pregnant women, or non-pregnant women with SARS-CoV-2 infection. Now that vaccination is available and rapidly getting implemented worldwide, the question arises whether pregnant women should be vaccinated, and if so, whether they should get priority. Methods. Available scientific data and available guidelines about vaccination against SARS-CoV-2 were collected by the Guideline Committee of the International Society of Infectious Diseases in Obstetrics and Gynecology (ISIDOG), and were analyzed, discussed and summarized as guidelines for health care workers caring for pregnant women. Concluding statements were graded according to the Oxford Evidence Based Medicine Grading System. Results. There is evidence to consider pregnancy as a risk factor for serious complications of COVID-19 infection, even in the absence of additional risk factors, such as hypertension, diabetes and obesity which increase these risks even more in pregnancy. Currently available data slightly favor mRNA-based vaccines above vector-based vaccines during pregnancy and breastfeeding, until more safety data become available. Conclusion. ISIDOG advices policy makers and societies to prioritize pregnant women to receive vaccination against SARS-CoV-2, and favor the mRNA vaccines until further safety information becomes available.

In tropical areas, simultaneous transmission of several vector-borne diseases is common due to ecological factors that are shared by arthropod vectors. Malaria and dengue virus, transmitted by Anopheles and Aedes mosquitoes, respectively, are among the top vector-borne diseases that cause significant morbidity and mortality in endemic areas. Notably, tropical areas often have suitable conditions for the co-existence of these mosquito species, highlighting the importance of identifying markers that accurately indicate the risk of acquiring each specific disease entity. Aedes are daytime-biting mosquitoes, while Anopheles preferentially bite during the night. These biting patterns raises the possibility of concurrent exposure to bites from both species. This pattern is important since mosquito saliva, deposited in the skin during blood feeding, induces immune responses that modulate pathogen establishment and infection. Previous studies have focused on characterizing such effects on the vector-pathogen interface for an individual pathogen and its mosquito vector. In this study, we evaluated associations between immune responses to salivary proteins from non-dengue and non-malaria vector mosquito species with clinical characteristics of malaria and dengue, respectively. Surprisingly, antibody responses against Anopheles antigens in dengue patients correlated with red blood cell count and hematocrit, while antibody responses against Aedes proteins were associated with platelet count in malaria patients. Our data indicate that concurrent exposure to multiple disease-carrying mosquito vectors and their salivary proteins with differing immunomodulatory properties could influence the transmission, pathogenesis, and clinical presentation of malaria, dengue fever, and other vector-borne illnesses.

Scheduling and optimization have a central place in the research area of computing because it is increasingly important to achieve fully automated production processes to adjust manufacturing systems to the requirements of Industry 4.0. In this paper, we demonstrate how an automated wet-etch scheduling problem for a semiconductor industry can be solved by constraint answer set programming (CASP) and, its solver called clingcon. The considered scheduling problem includes a robot for lot transfers between the baths. CASP is a hybrid approach in automated reasoning that combines different research areas such as answer set programming, Constraint Processing and Satisfiability Modulo Theories. For a long time, exact methods such as constraint programming have displayed difficulties in solving real large-scale problem instances. Currently, the performance of state-of-the-art constrains solvers is comparatively better than a decade ago, and some complex combinatorial problems can be optimally solved. These theoretical and technical achievements open new horizons for declarative programming applications such as logistics. A successful solution to this problem is achieved and we found that in most cases tested, CASP is faster and obtains in most cases similar makespan values than solutions based on mixed integer linear programming and constraint paradigms.

Underwater wireless sensor networks (UWSNs) represent a specialized category of WSNs with versatile applications including acoustic monitoring, oil and gas exploration, and military surveillance. UWSNs face formidable challenges such as limited energy resources, extended propagation delays, and harsh conditions. Existing clustering and multi-hop routing protocols often unevenly distribute nodes geographically, causing network fragmentation and disproportionately draining the battery life of nodes near the sink due to higher data transmission demands. In this paper, we introduce an Energy-efficient Artificial Fish Swarm-based Clustering Protocol (EAFSCP), inspired by the collective behavior of fish swarms. EAFSCP is a decentralized clustering algorithm designed for acoustic monitoring in UWSNs. Its decentralized nature makes it particularly well-suited for large-scale UWSNs, where centralized algorithms may not be feasible. Through comprehensive comparisons with existing cluster-based routing protocols, our findings indicate that EAFSCP consistently outperforms them across multiple key performance metrics, including network lifetime, energy consumption, packet delivery ratio, packet loss rate, and throughput. According to the results, EAFSCP represents an effective clustering algorithm that enhances network performance, prolongs network lifespan by reducing energy consumption, promotes scalability, and provides valuable guidance for emergency response efforts.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Objective: To evaluate two different DECT postprocessing protocols for detection of MSU deposits in foot tendons of cadavers with verification by polarizing light microscopy as gold standard.Material and Methods: A total of 40 embalmed cadavers (15 male; 25 female; median age, 82 years; mean, 80 years; range, 52 - 99; SD ± 10.9) underwent DECT to assess MSU deposits in foot tendons.Two postprocessing DECT protocols with different Hounsfield unit (HU) thresholds 150/500 (=established) versus 120/500 (= modified) HU were applied to dual source acquisition with 80 kV for tube A and 140 kV for tube B.Six fresh cadavers (4 male; 2 female; median age, 78; mean, 78,5; range 61 - 95 ) were examined by DECT. Tendon dissection of 2/6 fresh cadavers with positive DECT 120 and negative DECT 150 studies were used to verify MSU deposits by polarizing light microscopy.Results: The tibialis anterior tendon was found positive in 57.5%/100% (DECT 150/120), peroneus tendon in 35%/100%, achilles tendon in 25%/90%, flexor halluces longus tendon in 10%/100%, and tibialis posterior tendon in 12.5%/97.5%. DECT 120 resulted in increased tendon MSU deposit detection, when DECT 150 was negative, with an overall agreement between DECT 150 and DECT 120 of 80 % (P = 0.013). Polarizing light microscope confirmed MSU deposits detected only by DECT 120 in tibialis anterior, achilles, flexor halluces longus and peroneal tendons.Conclusion: The DECT 120 protocol showed a higher sensitivity when compared to DECT 150.

With the growing hope that disease-modifying treatments could target the molecular basis of neurodegenerative diseases even before the onset of symptoms, there is mounting pressure to define disease entities based on pathophysiology rather than on clinical syndromes. The Alzheimer’s disease research community has recently transitioned from diagnostic criteria based on an amnestic syndrome to a purely biomarker-based disease definition, relying on the demonstration of amyloid-beta pathology, tau pathology, and neurodegeneration. In contrast, current diagnostic criteria for Parkinson’s disease still rely on the presence of the well-described clinical syndrome of parkinsonism, with the addition of characteristic motor- and non-motor signs and symptoms. However, there is now unequivocal evidence that Parkinson’s disease starts years before the onset of parkinsonism. Furthermore, neuropathologically defined Lewy body disease is clinically heterogeneous, combining a range of motor, non-motor, dopaminergic and non-dopaminergic features. Finally, clinically defined Parkinson’s disease has diverse underlying etiologies most, but not all, associated with α-synuclein positive Lewy pathology. In light of recent scientific advances, we propose a biologically based definition for the diagnosis of Parkinson's disease, initially to be used for research purposes. The criteria use a three-component ‘G-S-N’ system. The first is documentation of defined gene variants (‘G’), which cause or strongly predispose to PD as the most upstream component. The second is α-synuclein pathology (‘S’), currently defined as pathological α-synuclein deposition in tissue or positive α-synuclein seeding assays. The third is evidence of underlying neurodegeneration (‘N’), currently defined by specific neuroimaging procedures. The associated clinical syndrome (‘C’) is defined by a single high-specificity feature or multiple lower-specificity features. Initiating this transition will enable the field to fuel both basic and clinical research and move closer to the precision medicine required to develop clinically meaningful disease-modifying therapies. We acknowledge current limitations, ethical implications, and the need for prospective validation of this approach.

Electrochemical energy conversion and storage is key for the use of regenerative energies at large scale. A thorough understanding of the individual components, such as the ion conducting membrane and the electrode layers, can be obtained with scattering techniques on atomit to molecular length scales. The largely heterogeneous electrode layers of High-Temperature Polymer Electrolyte Fuel Cells are studied in this work with small- and wide-angle neutron scattering at the same time with the iMATERIA diffractometer at the spallation neutron source at J-PARC, opening a view on structural properties on atomic to mesoscopic length scales.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

This article introduces a novel nature-inspired metaheuristic algorithm called Frilled Lizard Optimization (FLO), which emulates the hunting behavior of frilled lizards in their natural habitat. FLO draws in-spiration from the sit-and-wait strategy observed in frilled lizards during hunting. The underlying theory of FLO is presented and mathematically formulated in two phases: (i) an exploration phase, simulating the frilled lizard's attack towards prey, and (ii) an exploitation phase, simulating the lizard's retreat to the top of the tree after feeding. To assess FLO's efficacy in solving optimization problems, the algorithm's performance is evaluated across fifty-two standard benchmark functions, encompassing unimodal, high-dimensional multimodal, fixed-dimensional multimodal, and the CEC 2017 test suite. Comparative analyses with twelve existing metaheuristic algorithms are conducted. The simulation results reveal that FLO, distinguished by its adeptness in exploration, exploitation, and balancing them during search process, outperforms competing algorithms. Additionally, FLO is implemented on twenty-two constrained optimization problems from the CEC 2011 test suite and four engineering design problems, demonstrating its effectiveness in addressing real-world optimization applications.

Illumina and nanopore sequencing technologies are powerful tools that can be used to determine the bacterial composition of complex microbial communities. In this study, we compared nasal microbiota results at genus level using both Illumina and nanopore 16S rRNA gene sequencing. We also monitored the progression of nanopore sequencing in the accurate identification of species, using pure, single species cultures, and evaluated the performance of the nanopore EPI2ME 16S data analysis pipeline. Fifty-nine nasal swabs were sequenced using Illumina MiSeq and Oxford Nanopore 16S rRNA gene sequencing technologies. In addition, five pure cultures of relevant bacterial species were sequenced with the nanopore sequencing technology. The Illumina MiSeq sequence data were processed using bioinformatics modules present in the Mothur software package. Albacore and Guppy base calling, a workflow in nanopore EPI2ME and an in house developed bioinformatics script were used to analyze the nanopore data. At genus level, similar bacterial diversity profiles were found, and five main and established genera were identified by both platforms. However, probably due to mismatching of the nanopore sequence primers, the nanopore sequencing platform identified Corynebacterium in much lower abundance compared to Illumina sequencing. Further, when using default settings in the EPI2ME workflow, almost all sequence reads that seem to belong to the bacterial genus Dolosigranulum and a considerable part to the genus Haemophilus were only identified at family level. Nanopore sequencing of single species cultures demonstrated at least 88% accurate identification of the species at genus and species level for 4/5 strains tested, including improvements in accurate sequence read identification when the basecaller Guppy and Albacore, and when flowcell versions R9.4 and R9.2 were compared.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in alkaline medium. Their conversion to 5-substituted -hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted -aminoketones or a single -diketone. The new compounds were characterized by spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Malaria is a serious infection affecting millions of people in Africa. Our study investigated the personal preferences and applications of antimalarial medicines in Ghana. Based on over 1000 questionnaires distributed in Ghana from January to May 2019, we noticed that although Western medications to fight this disease are widely available, most patients in Ghana prefer treatment with locally produced herbal remedies. This preference appears to be due to a combination of traditional venues for obtaining medicines “on the street” rather than in licensed pharmacies, trust in local and “green” products, extensive advertisement of such local products, and an inherent distrust of imported and synthetic or unnatural medicines. Going local and natural is a trend also observed in other countries across the globe, and adds to the acceptance or rejection of drugs regardless of their activity or toxicity. In fact, adverse side effects associated with herbal remedies, such as general weakness and swollen, sore mouth, do not seem to deter the respondents of this study in Ghana. We propose a combination of (a) increasing public awareness of the benefits of modern medicine and (b) an improvement and control of the quality of herbal remedies to raise the standard of malaria treatment in countries such as Ghana.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor treatment response and clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient-matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient-matched liver metastases.

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

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used thirty-five monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied onto the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 45 minutes and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 °C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0 (https://gets.shinyapps.io/ABID/). This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 functionalized gold nanoparticles (AuNPs) for tumor specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities, but not on corresponding normal tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

Background and objective: The impairments and duration of PASC (Post-acute sequelae of COVID-19) symptoms in mental health have up to date not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course. Methods: Mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University-Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID-Syndrome-Score), depression (Patient-Health-Questionnaire 9), somatic symptoms (Patient-Health-Questionnaire 15), anxiety (Generalized-Anxiety-Disorder 7), fatigue (Fatigue-Severity-Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional-Malaise Screening) was conducted in the home environment. Results: 80% of patients experienced severe PASC at follow up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety, and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained on an unchanged high level. Risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre. Conclusion: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for mental health implications of PASC is needed for planning health services and disease prevention.

Idiopathic lung fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates in a reactive manner all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by Lysotracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial Lysotracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s which behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expresses AEC2s and basal cell markers resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of Lysotracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5 and CD24 expression in human lung epithelial cells. Combining functional analysis with extra- and intra- cellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.

Classical non-homologous end joining (NHEJ) is a molecular pathway that detects, processes and ligates DNA double-strand breaks (DSBs) throughout the cell cycle. Mutations in several NHEJ genes result in neurological abnormalities and immunodeficiency both in humans and mice. The NHEJ pathway is required for the V(D)J recombination in developing B and T lymphocytes, and for class switch recombination in mature B cells. Ku heterodimer formed by Ku70 and Ku80 recognizes DSBs and facilitates the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, Paxx and Mri/Cyren) and downstream core factors subunits XLF, XRCC4 and Lig4. Accessory factors might be dispensable for the process depending on the genetic background and DNA lesion type. To determine the physiological role of Mri in DNA repair and development, we introduced frame-shift mutation in the Mri gene in mice. We then analyzed the development of Mri-deficient mice as well as wild type and immunodeficient controls. Mice lacking Mri possessed reduced levels of class switch recombination in B lymphocytes and slow proliferation of neuronal progenitors when compared to wild type littermates. Human cell lines lacking Mri were as sensitive to DSBs as WT controls. Overall, we concluded that Mri/Cyren is largely dispensable for DNA repair and mouse development.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

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 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.

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.

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.