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

Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are safe and effective in pregnancy. There are no Mexican surveys in physicians on knowledge, beliefs, and practices towards influenza and influenza immunization during pregnancy. A 32 questions cross-sectional and descriptive survey was conducted addressing general knowledge of influenza, as well as beliefs and practices regarding influenza vaccination during pregnancy among Mexican physicians responsible for prenatal care, traditionally Obstetricians (OBGYNs), and Family Physicians (FPs). A total of 206 surveys were available, 98 (47.6%) from OBGYNs, and 108 (52.4%) from FPs representing an estimated 2,472 daily pregnancy consultations. 54 from 206 (26.2%) weren´t aware that influenza is more severe during pregnancy, 106 from 206 (51.5%) ignored the potential side effects of influenza infection on the fetus, and 56.8% did not know when to vaccinate pregnant women. Pregnancy as a risk factor for developing influenza complications was known only by 99 from 206(48.1%), and 6.1 % believed that vaccination does not confer protection to the fetus. Current beliefs of Mexican OBGYNs and FPs for both influenza morbidity and mortality, and the importance of influenza vaccination during pregnancy, is suboptimal. Understanding drivers for beliefs should be assessed to improve influenza vaccination recommendations, as knowledge alone is not sufficient.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

Intrusion Detection Systems (IDS) plays a part in modern cyber security, as a result of the increasing need for cyber security systems in the “real” world due to the increasing number of cyber attacks, more sophisticated systems are required in order to prevent these attacks - an IDS can provide this protection. Due to the sophistication of these systems, they must be properly understood, developed and analyzed - research papers can be used as a tool to improve IDS systems. This paper is composed of two main sections: a survey and a taxonomy, providing information, reviews and interpretations from relevant papers, a timeline of important papers, a discussion on the future of IDS and a classification on IDS and how to apply this.

The existing segmentation-based scene text detection methods mostly need complicated post-processing, and the post-processing operation is separated from the training process, which greatly reduces the detection performance. The previous method, DBNet successfully simplified post-processing and integrated the post-processing into a segmentation network. However, the training process of the model took a long time for 1200 epochs and the sensitivity to texts of various scales was lacking, leading to some text instances being missed. Considering the above two problems, we design the text detection Network with Binarization of Hyperbolic Tangent(HTBNet). First of all, we propose Binarization of Hyperbolic Tangent (HTB), optimized along with which, the segmentation network can expedite the initial convergent speed by reducing the amount of epochs from 1200 to 600. Because features of different channels in the same scale feature map focus on the information of different regions in the image, to better represent the important features of all objects in the image, we devise the Multi-Scale Channel Attention(MSCA). Meanwhile considering that multi-scale objects in the image cannot be simultaneously detected, we propose a novel module named Fused Module with Channel and Spatial(FMCS), which can fuse the multi-scale feature maps from channel and spatial dimension. Finally we adopt cross entropy as the loss function, which measures the difference between predicted values and ground truths. The experimental results show that HTBNet compared with lightweight models has achieved competitive performance and speed on Total-Text(F-measure:86.0%, FPS:30) and MSRA-TD500 (F-measure:87.5%, FPS:30).

Stable half-sandwich iron(II) dihalido complexes of the type [Fe(5-Cp’)X2] are extremely scarce, being limited to congeners containing the bulky C5H2-1,2,4-tBu3 ligand. We have extended this to homologues [Fe(5-Cp*)X2] (X = Cl – I) containing the particularly popular C5Me5 (Cp*) ligand. Corresponding ionic compounds ER4[Fe(5-Cp*)X2] are easily accessible from FeX2, MCp* (M = Li, K) and a suitable halide source R4EX (E = N, P) in THF. The new compounds NnPr4[Fe(5-Cp*)X2] (X = Cl, Br), NnPr4[Fe(5-Cp*)BrCl] and PPh4[Fe(5-Cp*)X2] (X = Cl, Br, I) have been structurally characterised by single-crystal X-ray diffraction. NnPr4[Fe(5-Cp*)Cl2] reacts readily with CO to afford [Fe(5-Cp*)Cl(CO)2], indicating the synthetic potential of ER4[Fe(5-Cp*)X2] in FeCp* half-sandwich chemistry.

：Non-Euclidean data, such as social networks, and citation relationships between documents, has node information and structural information. Graph Convolutional Network(GCN) can automatically learn node features and association information between nodes. The core ideology of the graph convolutional network is to aggregate node information by using edge information, thereby generating a new node feature. In the process of updating node features, there are two core influencing factors. One is the number of neighboring nodes of the central node, the other is the contribution of the neighboring nodes to the central node. Due to the previous GCN methods not simultaneously considering the numbers and different contributions of neighboring nodes to the central node, we design the Adaptive Attention Mechanism(AAM). To further enhance the representational capability of the model, we utilize Multi-Head Graph Convolution(MHGC). Finally, we adopt cross-entropy(CE) loss function to describe the difference between the predicted results of node categories and the ground truth (GT). Combined with backpropagation, this ultimately achieves accurate node classification. Based on AAM, MHGC and CE, we contrive the novel Graph Adaptive Attention Network (GAAN). Experiments show that the classification accuracy has achieved outstanding performances on Cora, Citeseer and Pubmed datasets.

There is a large potential for cost-effective solutions to reduce greenhouse gas emissions and to improve the sustainability of the transport sector that is yet unexploited, in particular in the urban context. Considering the cost-effectiveness and the potential for co-benefits, it is hard to understand why energy gains and mitigation action in the transport sector is still lagging behind the potential. Particularly interesting is the fact that there is substantial difference among countries with relatively similar economic performances, such as the OECD countries in the development of their transport CO2 emission over the past thirty years despite the fact that these countries had relatively similar access to efficient technologies and vehicles. This study aims to apply some well established political science theories on the particular example of climate change mitigation in the transport sector in order to identify some of the factors that could help explain the variations in success of policies and strategies in this sector. The analysis suggests that institutional arrangements that contribute to consensus building in the political process provide a high level of political and policy stability which is vital to long-term changes in energy end-use sectors that rely on long-term investments. However, there is no direct correlation between institutional structures, e.g. corporatism and success in reducing greenhouse gas emissions in the transport sector. Environmental objectives need to be built into the consensus-based policy structure before actual policy progress can be observed. This usually takes longer in consensus democracies than in politically more agile majoritarian policy environments, but the policy stability that builds on corporatist institutional structures is likely to experience changes over a longer-term, in this case to a shift towards low-carbon transport that endures.

Global stress is widespread in todays post-pandemic world of political and economic uncertainty. Vibroacoustic technology is a vibrotactile intervention with multiple uses, and its impact on stress lacks interpretation. This research assessed if the vibroacoustic technology of a Vibroacoustic Sound Massage (VSM) can reduce psychological, physiological and cognitive stress. The Perceived Stress Scale (PSS-10), and electrocardiogram (ECG) and electroencephalogram (EEG) biosignals were used to quantify results. Participants were divided into Low Stress and High Stress groups. ECG results show VSM increased parasympathetic activity for all participants, with the Low Stress group more effected. EEG results indicate increased concentration (TBR), reduced arousal and increased relaxation (BAR), and non-significant effects on participant well-being (FAA), though variability in this metric was homogenised after VSM. Together, these results validate VSM as an effective support tool for stress management and further research is required.

Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we explored the response of green and red leaf lettuce cultivars (’Aquino’, CVg, or ‘Barlach’, CVr, respectively) to long-term blue-enriched light application (WB). Plants were grown for 30 days in a growth chamber with optimal environmental condi-tions (temperature: 20°C, relative humidity: 60%, ambient CO2, Photon Flux Density (PFD) of 260 µmol m-2 s-1 over an 18-h photoperiod). At 15 days after sowing (DAS) white spectrum LEDs (WW) were compared to WB (λPeak = 423 nm) maintaining the same PFD of 260 µmol m-2 s-1. At 30 DAS, both lettuce cultivars resulted adapted to the blue light variant, though the adaptive re-sponse was specific to the variety. Rosette weight, light use efficiency and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. Significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and, on the modified anthocyanin re-flectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was gen-erally stronger in CVg compared to CVr; e.g. net photosynthetic rate, Pn, at 1000 µmol m-2 s-1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. Results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.

This paper presents a comparison of two methods to represent variable blade inertia in two codes for aero-servo-elastic simulations of wind turbines: the nonlinear aeroelastic multi-body model HAWC2 and the nonlinear geometrically exact beam model BeamDyn for OpenFAST. The main goal is to enable these tools to simulate the dynamic behavior of a wind turbine with variable blade inertia. However, in order to simulate the structural response of wind turbines with variable blade inertias, the source code of load simulation tools need to be modified. This is due to the fact that, currently, state-of-the-art load simulation tools for wind turbines are unable to simulate variable rotor blade inertias. The validity of the modified codes is proven based on a simple beam model. The validation shows very good agreement between the modified codes of HAWC2, BeamDyn and an analytical calculation. The add-on of variable blade inertias is applied to reduce the mechanical loads of a 5 megawatt reference wind turbine with an integrated hydraulic-pneumatic flywheel in its rotor blades.

Land degradation is a serious impediment to improving rural livelihoods in Eastern Africa. This paper identifies major land degradation patterns and causes, and analyzes the determinants of sustainable land management (SLM) in three countries (Ethiopia, Malawi and Tanzania). The results show that land degradation hotspots cover about 51%, 41%, 23% and 23% of the terrestrial areas in Tanzania, Malawi and Ethiopia respectively. The analysis of nationally representative household surveys shows that the key drivers of SLM in these countries are biophysical, demographic, regional and socio-economic determinants. Secure land tenure, access to extension services and market access are some of the determinants incentivizing SLM adoption. The implications of this study are that policies and strategies that facilities secure land tenure and access to SLM information are likely to incentivize investments in SLM. Local institutions providing credit services, inputs such as seed and fertilizers, and extension services must also not be ignored in the development policies.

Few studies have examined the pros and cons of integrated TB and HIV service delivery in public healthcare facilities, and even fewer have proposed conceptual models for improved integration. This study intends to fill that vacuum by outlining the development of a facility-based paradigm for integrating TB, HIV and patients services. The design of the proposed model were in stages that involved the evaluation of existing TB-HIV integration model and synthesis of both quantitative and qualitative data from the study sites which were selected public healthcare facilities at both rural and peri-urban settings in Oliver Reginald (O.R) Tambo District Municipality in Eastern Cape, South Africa. Secondary data on 2009-2013 TB-HIV clinical outcomes were obtained from multiple sources for quantitative analysis. Qualitative data involved focus group discussions among patient and heath care staff, which was thematically analysed. The development of a possibly better model and validation of this model show that the district's health system was reinforced by the model's guiding principles, which placed a strong emphasis on inputs, processes, outcomes, and integration effects.The model is adaptable to different healthcare delivery systems but will require support from healthcare stakeholders and professionals to be successful.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards a more and urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life-cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted in Austria. Individual partworth utilities were estimated by means of Hierarchical Bayes. Results show higher WTP for a positive evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negative evaluated multi-level label showed higher WTP compared to no label, pointing towards limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preferences for animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging and sustainability labels have only a small impact on the meat product choice of average consumers.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

With the evolution of toxic chemicals continuing to progress, developing methods for the destruction of chemical warfare agents (CWAs) has become an increasingly important research topic. Metal-organic frameworks (MOFs) are a class of porous crystalline solids that have sparked interest in this area. Due to their exceptional porosities and large surface areas, MOFs possess superior adsorption, reactivity, and catalytic abilities, making them structurally ideal candidates for the capture and decomposition of target species. Additionally, the tunable networks of MOFs allow their chemical functionalities to be customized for various applications and operating conditions, making them practicable in personal protective equipment and adjustable to dynamic environments. This paper reviews experimental and computational studies on CWA removal by MOFs, with a special emphasis on nerve agent (GB, GD, and VX) removal via hydrolysis and sulfur mustard (HD) removal via selective photooxidation. With extraordinary structural stability and reusability, zirconium-based MOFs are the most promising materials for hydrolytic and photooxidative degradation of CWAs and are thus the primary focus of this work. First-principles approximations of the intrinsic catalytic reaction mechanisms towards different agents in Zr-MOFs are summarized, and developments in the structure-property relationships governing Zr-MOF design rules for efficient degradation in the aqueous and solid phases are discussed. We also examine recent progress in tuning and functionalizing MOFs to promote practical CWA removal under realistic battlefield conditions.

Plasmodium vivax causes the second highest number of malaria morbidity and mortality cases in humans. Several biological traits of this parasite species, including the formation of dormant stages (hypnozoites) that persist inside the liver for prolonged periods of time, present an obstacle for intervention measures and create a barrier for the elimination of malaria. Research into the biology of hypnozoites requires efficient systems for parasite transmission, liver stage cultivation and genetic modification. However, P. vivax research is hampered by the lack of an in vitro blood stage culture system, rendering it reliant on in vivo derived, mainly patient material, for transmission and liver stage culture. This has also resulted in a limited capability for genetic modification, creating a bottleneck in investigations into the mechanisms underlying the persistence of the parasite inside the liver. This bottleneck can be overcome through optimal use of the closely related and experimentally more amenable nonhuman primate (NHP) parasite Plasmodium cynomolgi as model system. In this review we discuss the genetic modification tools and liver stage cultivation platforms available for studying P. vivax persistent stages and highlight how their combined use may advance our understanding of hypnozoite biology.

The question of building sustainable in a geographical locality is inexorably linked to cost. In 2011, one of the authors built a sustainable house that was (at the time) the highest certified sustainable home based on the National Association of Home Builder’s standards for sustainable construction. This Texas house has been used for residential and research purposes for the past decade. In this case study, the authors evaluate components of the construction and their effectiveness as well as unseen secondary and tertiary effects. Some of the specific components discussed are home site placement; rainwater harvesting (100% of residential requirements); aerobic septic system; grid-tied solar array power; electric car charging; geothermal heating and cooling; reclaimed wood framing; spray foam installation; selection of windows, fixtures, and appliances; on-demand electric water heaters for guest areas; generator backups; and use of local items. Electric bills and water system improvements are discussed in detail, as improvements were made as part of residential and research requirements. This case study suggests that the financial outlay is worth the extra up-front costs if residents in this geographical area and climate will occupy the residence 7 years.

Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement. Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.

This article discusses the outcomes of a quantitative analysis of the competitiveness of grain and its recycling in the countries-members of the Eurasian Economic Union (EEU) through econometric panel data models. The analysis is based on the data of public authorities’ statistics of the countries-members of the EEU, as well as the United Nations Comtrade Database which is a repository of official international trade statistics. The results of the analysis allow to assess the level of competitiveness of produced agro-food products in the countries-members of the EEU and determine the extent to which various factors affect it. The research conclusions can be used to develop and adjust the agreed with the agro-food policy in the EEU.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

High temperatures (HT) and high hydrostatic pressures (HHP) are characteristic of deep-sea hydrothermal vents and other deep crustal settings. These environments host vast and diverse microbial populations, yet only a small fraction of those populations have been successfully cultured. This is due, in part, to the difficulty of sampling while maintaining these in situ conditions and also replicating those high-temperature and high-pressure conditions in the laboratory. In an effort to facilitate more HT-HHP cultivation, we present two HT-HHP batch culture incubation systems for cultivating deep-sea vent and subsurface (hyper)thermophilic microorganisms. One HT-HHP system can be used for batch cultivation up to 110 MPa and 121°C, and requires sample decompression during subsampling. The second HT-HHP system can be used to culture microorganisms up to 100 MPa and 160°C with variable-volume, pressure-retaining vessels that negate whole-sample decompression during subsampling. Here, we describe how to build cost effective heating systems for these two types of high-pressure vessels, as well as the protocols for HT-HHP microbial batch cultivation in both systems. Additionally, we demonstrate HHP transfer between the variable-volume vessels, which has utility in sampling and enrichment without decompression, laboratory isolation experiments, as well as HHP filtration.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

The planning of bicycle infrastructure across our cities remains is a complex task involving many key stakeholders including the community, who traditionally have had limited involvement in the planning process. This research develops an interactive bicycle prioritisation index tool which includes participatory spatial and textual citizen feedback. The research involves three components. Firstly, a survey of current cyclists in Sydney, their current level of participation, priorities in investment in cycling, and preferred locations for cycling infrastructure. Secondly, it documents the development of an interactive digital bicycle planning tool which is informed through citizen feedback. Thirdly, it evaluates the approach in conversation with potential end-users, including government, planning practitioners, and advocacy group members. The research proposes the combination of multiple passive and active data traces with end-user evaluation to legitimise the citizen co-design of bicycle investment prioritisation initiatives. A case study approach has been taken, focusing on the city of Sydney, Australia. The bicycle planning support system can be used by cities when engaging in cycle prioritisation initiatives, particularly with a focus on integrating citizen feedback and navigating new and complex data landscapes introduced through recent, passively collected big data sets.

Intensive application of synthetic pesticides was the routine practice of commercial agriculture during the Green Revolution to boost agricultural productivity to meet global food demand. Alongside this, the application of chemical pesticides caused adverse effects on the environment and its ecoreceptors including human health. Negative externalities arising from conventional farming instigated the call for sustainable development during the sixties to promote and balance the nexus between socially acceptable economic growth and environmental protection. Consequently, a blueprint of 17 Sustainable Development Goals (SDGs) and 169 targets including ecological stewardship and food security was drafted. Eight out of the 17 SDGs are directly linked to sustainable agriculture based on the direct impact of agriculture, judicious use of critical resources and conservation and the Principles of green chemistry. As a green chemical agent, biopesticides have been shown to have the potentials to substitute chemical pesticides with equal agricultural productivity. The adoption of bio-based pesticides via integrated pest management (IPM) has proven to be the most effective option to influence most dimensions of sustainable agriculture. Therefore, biopesticide-driven IPM if utilized with requisite education, skills and research would boost sustainable agriculture. This chapter reviews the prospects, importance, and limitations of biopesticides to sustainable agriculture and how sustainable agriculture is connected to sustainable development, Green Chemistry, and integrated pest management.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

Within this paper, electro-mechanical long-term tests on a thrust bearing are presented. The effects of an additional electrical load on the bearing raceways and the used lubricant are investigated. Chemical and rheological investigations are presented which show the changes in the lubricant. These investigations are compared with the electrical loads and the occurring raceway damage. In addition, a comparison is made with mechanical reference tests. This procedure makes it possible to classify the changes that occur due to the electrical load and to distinguish the effects from each other. The background to these investigations is the increased occurrence of parasitic currents in electric motors, which can lead to damage to machine elements. The phenomena that occur here are new challenges in the development of drive trains.

With its sights set on sustainable development, transport policy finds itself confronted with the challenge of convincing people to abandon the current path of growth and instead use small, slower vehicles with a reduced range in the future. The problem with this goal is that people's mental structures are shaped by the car ensconced in their heads. Thinking in other terms hardly seems possible; moreover, many of the products classified as vehicles, but smaller in scale than the "car" and that already exist, remain unknown, nor can they be tried out - they are quite literally nowhere to be seen. In light of this situation, the German Federal Environmental Foundation has commissioned a feasibility study to explore the establishment of a World of Experience (Erlebniswelt) of sustainable urban mobility - the EcoMobileum®. Here, the aim is to open up the horizons of a new culture of mobility in order to get people excited about the transformation of mobility.

Most recent university campuses follow the North American model, built on city limits or countryside, with large separate buildings in open green spaces. Studies suggest that prevalence and severity of mental health issues among university students are increasing over the past decade in most countries. University services were created to face this growing problem, however individual based interventions have limited effects on mental health and well-being of a large population. Our aim was to verify if and how the natural environment in Campuses is focused on programs to cope with the issue of mental health and well-being among students. Systematic review of literature was undertaken with search in Scopus and LILACS with the keywords “green areas” AND “well-being” AND “Campus”, following PRISMA guidelines. As a result, 32 articles were selected. Research on the topic is recent, mostly in the USA, Bulgaria, and China. Most studies used objective information on campuses’ greenness and/or university students’ perception. Mental health was usually measured by validated scores. Findings of all the studies indicated positive association between campus greenery and well-being of students. We conclude that there is a large potential for use of university campuses in programs and sites for students´ restoration and stress relief.

Pearl millet (Pennisetum glaucum L.) is the second most important cereal grown in Eritrea after sorghum (Sorghum bicolor L.) grown under low input systems by small scale farmers. The crop utilizes soil moisture efficiently and has ability to tolerate soil toxicity and extreme temperatures than other cereals. It is a sustenance and food security crop important for its nutritive and cultural value and provides dietary energy and nutrition. However, despite the positive attributes and qualities of pearl millets for the present and future agriculture, production has been low. We attribute this to inadequate rainfall distribution, poor crop management by poorly resourced farmers, unavailability and high prices of farm inputs such as fertilizer and pesticides and low adoption of improved varieties by the farmers. This review outlines the constraints, interventions the government/ farmers have and can implement and the prospects of actions that can improve pearl millet production. As much as there have been efforts by the government and stakeholders to address these challenges and improve productivity of pearl millet, more needs to be done to meet the increasing demand of the increasing populations. This will enable farmers to intensify and diversify their agricultural systems and improve food security situation in the country. Unless a combined effort in soil fertility improvement, policies to promote use of modern varieties and conservation of and promotion of this crop biodiversity, the potential of this crop as famine and poverty alleviation among the rural poor will not be realized.

We present a compact optical head design for wide-range and low noise displacement sensing using deep frequency modulation interferometry. The on-axis beam topology is realised in a quasi-monolithic component and relies on cube beamsplitters and beam transmission through perpendicular surfaces to keep angular alignment constant when operating in air or vacuum, which leads to the generation of ghost beams that can limit the phase readout linearity. We investigate the coupling of these beams into the non-linear phase readout scheme of DFMI and demonstrate adjustments of the phase estimation algorithm to reduce this effect. This is done through a combination of balanced detection and the inherent orthogonality of beat signals with different relative time-delays in deep frequency modulation interferometry that is a unique feature not available for heterodyne, quadrature or homodyne interferometry.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

Extensive phytochemical and chromatographic analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) resulted in the isolation and identification of 22 distinct secondary metabolite compounds. Two new compounds, 6-hydroxy-8-methoxycoumarin-7-O-β-D-glycopyranoside and (3-(2-(methylamino) ethyl)-1H-indol-2-yl) methanol, were isolated and identified for the first time from a natural source. In addition, other known compounds, such as hovetricoside C and N-methyltryptamine were isolated from Euphorbiaceae, and hordenine, N-methyltyramine, their salts, cynaroside and linarin were identified in Jatropha spp. for the first time. Some isolated metabolites, such as β-sitosterol, β-sitosterol glucoside, curcusons D and C, naringenin, apigenin, cleomiscosins B and A, spruceanol, propacin, jatrophadiketone, and uracil were previously identified in various Jatropha species. The structures of the isolated compounds were determined using different spectroscopic techniques. The anti-inflammatory, antinociceptive, antipyretic, and antioxidant activities were evaluated for some adequately available isolated compounds. Compounds showed significant antinociceptive activity compared with the standard analgesic drug indomethacin. The edema size was significantly reduced (p< 0.05–0.001) in the animals treated with low doses (5 and 10 mg/kg) of the isolated compounds compared with those treated with a high dose (100 mg/kg) of standard anti-inflammatory drug (phenylbutazone). Furthermore, all tested compounds showed a significant (p< 0.05–0.001) reduction in the rectal temperature of hyper-thermic mice.

In the literature on occupational stress and recovery from work several facets of thinking about work in off-job time have been conceptualized. However, research on the focal concepts is currently rather disintegrated. In this study we take a closer look at the five most established concepts, namely (1) psychological detachment, (2) affective rumination, (3) problem-solving pondering, (4) positive work reflection, and (5) negative work reflection. More specifically, we scrutinized (1) whether the five facets of work-related rumination are empirically distinct, (2) whether they yield differential associations with different facets of employee well-being (burnout, work engagement, thriving, satisfaction with life, and flourishing), and (3) to what extent the five facets can be distinguished from and relate to conceptually similar constructs, such as irritation, worry, and neuroticism. We applied structural equation modeling techniques to cross-sectional survey data from 474 employees. Our results provide evidence that (1) the five facets of work-related rumination are highly related, yet empirically distinct, (2) that each facet contributes uniquely to explain variance in certain aspects of employee well-being, and (3) that they are distinct from related concepts, albeit there is a high overlap between (lower levels of) psychological detachment and cognitive irritation. Our study contributes to clarify the structure of work-related rumination and extends the nomological network around different types of thinking about work in off-job time and employee well-being.

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. Minerals were quantified by ICP-MS, myo-inositol phosphates (InsP₅, InsP₆) by HPLC ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP₆ was slightly decreased (7%) in one treatment. Bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.

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

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

Disorder of S-adenosylhomocysteine hydrolase (AHCY) activity leads to the potentially lethal rare disease AHCY deficiency, first described in 2004 by Baric and co-workers [1]. In order to shed new light on molecular aspects of the disease, in particular changes at transcriptome level, we enabled knock-down of AHCY expression in model systems such as the colon cancer cell line SW480 to simulate the environment occurring in AHCY deficiency patients. Further, we per-formed deep sequencing of mRNA, followed by differential expression and molecular pathway analysis. Fifteen differentially expressed networks were identified, and interestingly, we found a predicted effect of AHCY down-regulation on the expression of the Lymphoidphoid enhanc-er-binding factor 1 (LEF1) gene, indicating changes in the TCF4/LEF1 complex. LEF1, a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a down-stream mediator of the Wnt/β-catenin signaling pathway [2]. LEF1 is essential in stem cell maintenance, and especially in its role in epithelial-mesenchymal transition (EMT). Western blot analysis of LEF1 protein expression confirmed our transcriptomic data predictions and revealed significantly increased LEF1 protein in AHCY- deficient cells, providing a novel link between AHCY and cancer cell phenotype.

Today massive amounts of sequenced metagenomic and -transcriptomic data from different ecological niches and environmental locations are available. Scientific progress depends critically on methods that allow extracting useful information from the various types of sequence data. Here, we will first discuss types of information contained in the various flavours of biological sequence data, and how this information can be interpreted to increase our scientific knowledge and understanding. We argue that a mechanistic understanding is required to consistently interpret experimental observations, and that this understanding is greatly facilitated by the generation and analysis of dynamic mathematical models. We conclude that, in order to construct mathematical models and to test mechanistic hypotheses, time-series data is of critical importance. We review diverse techniques to analyse time-series data and discuss various approaches by which time-series of biological sequence data was successfully used to derive and test mechanistic hypotheses. Analysing the bottlenecks of current strategies in the extraction of knowledge and understanding from data, we conclude that combined experimental and theoretical efforts should be implemented as early as possible during the planning phase of individual experiments and scientific research projects.

Ketogenic diet (KD) is getting in the focus as auxiliary cancer therapy, since it provides sufficient energy supply for healthy cells, while impairing energy production in tumor cells underlying the Warburg effect. Thereby, it can assist in inhibiting tumor growth and simultaneously counteract cachexia, which is frequently observed in cancer patients under chemotherapy. In order to provide molecular evidence for the proposed synergistic inhibition of tumor growth, we applied untargeted quantitative metabolome analysis on a breast cancer xenograft mouse model. Healthy mice and such bearing breast cancer xenografts and receiving chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both, the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of KD in the context of tumor growth inhibition.

Although work events can be regarded as pivotal elements of organizational life, only a few studies have examined how positive and negative events relate to and combine to affect work engagement over time. Theory suggests that to better understand how current events affect work engagement (WE), we have to account for recent events that have preceded these current events. We present competing theoretical views on how recent and current work events may affect employees (e.g., getting used to a high frequency of negative events or becoming more sensitive to negative events). Although the occurrence of events implies discrete changes in the experience of work, prior research has not considered whether work events actually accumulate to sustained mid-term changes in WE. To address these gaps in the literature, we conducted a week-level longitudinal study across a period of 15 consecutive weeks among 135 employees, which yielded 849 weekly observations. While positive events were associated with higher levels of WE within the same week, negative events were not. Our results support neither satiation nor sensitization processes. However, high frequencies of negative events in the preceding week amplified the beneficial effects of positive events on WE in the current week. Growth curve analyses show that the benefits of positive events accumulate to sustain high levels of WE. WE dissipates in the absence of continuous experience of positive events. Our study adds a temporal component and informs research that has taken a feature-oriented perspective on the dynamic interplay of job demands and resources.

Novel strategies in coastal protection are needed to cope with climate change-induced sea level rise. They aim at the sustainable development of coastal areas in light of an intensification and land use changes. A promising approach is the design of nature-based solutions (NbS), complementing the safety levels of technical infrastructures. However, NbS lack a widespread and large-scale implementation. To address this deficit, co-design concepts are needed that combine experiences from science and practice. This work presents and discusses the approach of a coast-specific real-world laboratory (RwL) addressing the inclusive design of ecosystem-based coastal protection. Strategies of RwLs are applied for the first time in a coastal context along the North Sea coastline in Germany. We found the concept of RwLs suitable for coastal transdisciplinary research, although adaptions in the spatial reference level or flexibility in location and time of experimentation are necessary. A profound actor analysis is indispensable to specify participatory processes and interaction levels. A criteria-based cooperative selection of RwL sites helps to reveal and solve conflicting interests to achieve trust between science and practice. Addressing site-specific characteristics and practitioners’ needs, our coastal RwL provides a mutual learning space to develop and test NbS to complement technical coastal protection.

Recycled wastewater is considered as a sustainable source of irrigation water. Despite commendable safety records, viral contamination of agricultural products has occurred the past causing disease outbreaks. This review examines the apprehension that the novel coronavirus (SARS-CoV-2) may also spread through recycled wastewater irrigation (RWI) industry. The novel SARS-CoV-2 is now perceived as an enteric pathogen, and has been found to remain stable in the wastewater for days. Mounting evidences also suggest that viral particles shed by infected individuals through sewage, and greywater is much higher (up to 10 Log₁₀) than the amount typically removed (6-7 Log₁₀) through the recycled water disinfection processes. Such gap indicated an increased risk of infection through fecal-oral transmission route. This study also identified greywater irrigation schemes posing a higher risk of transmission of SARS-CoV-2. It was recommended that countries putting greywater in the ‘low risk’ category may rewrite the safety guidelines in post COVID-19 times. This review also suggest that the choice of irrigation method could be critical in protecting the farmers, and the consumers from possible infections during the pandemic. In this regard, irrigation methods (i.e. sprinkler) that generate airborne droplet (leading to aerosols) may be operated with caution when public spaces are in the vicinity. The study also indicated that the developing countries should regulate surface irrigation practice that pump water from polluted rivers during the pandemic.

The impact of organizational accreditation and professional certification and the evidence-based measurable impact of those for both academic programs and affiliates is one of specific interest to universities and individuals in the healthcare management field [1]. The authors’ analysis examined the impact of hiring graduates from higher education programs that held external accreditation from the Commission on Accreditation of Healthcare Management Education (CAHME). Graduates’ affiliation with the American College of Healthcare Executives (ACHE) professional healthcare leadership organization was also assessed as an independent variable. Study outcomes focused on these graduates’ respective healthcare organization’s performance measures (cost, quality, and access) to assess the researchers’ inquiry into the perceived value of a CAHME-accredited graduate degree in healthcare administration and a professional ACHE affiliation [2]. The results from this study found no effect of CAHME accreditation or ACHE affiliation on healthcare organization performance outcomes. The study findings support the need for future research surrounding healthcare administration professional graduate degree program characteristics and leader development affiliations, as perceived by various industry stakeholders.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

Knowledge about laminar-turbulent transition on operating multi-megawatt wind turbine blades needs sophisticated equipment like hot-films or microphone arrays. Contrarily thermographic pictures can easily be taken from the ground and temperature differences indicate different states of the boundary layer. The accuracy however, still is an open question, so that an aerodynamic glove known from experimental research on aero-planes was used to classify the boundary-layer state of a 2 megawatt wind turbine blade operating in the orthern part of Schleswig-Holstein, Germany. State-of-the-art equipment for measurering static surface pressure was used for monitoring the lift distribution. To distinguish laminar and turbulent parts of the boundary layer (suction side only) 48 microphones were applied together with ground-based thermographic cameras from two teams. Additionally, an optical camera mounted on the hub was used to survey vibrations. During start-up (from 0 to 9 rpm) extended, but irregularly shaped regions of a laminar boundary layer were observed which had the same extension measured both with microphones and Thermography. When an approximately constant rotor rotation (9 rpm corresponding to approximately 6 m/s wind-speed) was achieved, a flow transition was visible at the expected position of 40 % chord length on the rotor blade, which was fouled with dense turbulent wedges and an almost complete turbulent state on the glove was detected. In all observations, quantitative determination of the flow transition positions from thermography and microphones agree well within their accuracy.

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

Before the green revolution, crude plant materials and plant-extracts were used for crop protection. However, their use was swiftly replaced by synthetic pesticides after World War II due to increased demand for more effective pesticides in intensified farming systems. The 20th century saw a steady increase in the use of synthetic pesticides until the mid-21st century when the world started to realize the negative impact of synthetic pesticides. The increased environmental awareness and the need for safe human food led to increased research and development of biopesticides as crop protection options in modern agriculture. This paper brings into perspective the global history of the application and use of botanical biopesticides in crop production. It also highlights the research progress, product development and registration challenges, and opportunities for business and adoption at the farm level in Kenya.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

The growing awareness of the biological effects of artificial light on humans has stimulated ample research. It is now widely accepted that asynchrony between artificialand natural light-dark cycles can elicit severe detrimental health effects. New research has been devoted to lighting solutions that dynamically change their color to mimic spectral changes of daylight and to account for human needs. However, in some situations, the visual properties of light must be preserved: For example professional TV video editors and shift workers who must work under standardized lighting conditions to do color correction in post-production. We have investigated the possibility to tune circadian effects using white lights that are spectrally different but nonetheless have similar color coordinates thus appear as a similar white tone. Our simulation results indicate that it is possible to modulate circadian light effects by combining LEDs for neutral white (4000 K), a widely used white tone for indoor lighting in europe. The results also show that the solutions combining single-color LEDs do however not meet the quality criteria from the visual point of view because their color rendering ability decays to unacceptable low levels. Combining narrowband LEDs with a broadband white LED improves the color rendering quality and we show how far circadian light effects can be tuned according to common theoretical models. The aim is to reflect daylight situations with artificial lighting, thus having a high melatonin suppression in the morning and low melatonin suppression in the evening. As a consequence our aim is to show what maximum and minimum circadian effect is possible with the same set of LEDs.

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.

Identifying macroeconomic events that are responsible for dramatic changes of economy is of particular relevance to understand the overall economic dynamics. We introduce an open-source available efficient Python implementation of a Bayesian multi-trend change point analysis which solves significant memory and computing time limitations to extract crisis information from a correlation metric. Therefore, we focus on the recently investigated S&P500 mean market correlation in a period of roughly 20 years that includes the dot-com bubble, the global financial crisis and the Euro crisis. The analysis is performed two-fold: first, in retrospect on the whole dataset and second, in an on-line adaptive manner in pre-crisis segments. The on-line sensitivity horizon is roughly determined to be 80 up to 100 trading days after a crisis onset. A detailed comparison to global economic events supports the interpretation of the mean market correlation as an informative macroeconomic measure by a rather good agreement of change point distributions and major crisis events. Furthermore, the results hint to the importance of the U.S. housing bubble as trigger of the global financial crisis, provide new evidence for the general reasoning of locally (meta)stable economic states and could work as a comparative impact rating of specific economic events.

Originating in the 1970s, Magnetic Compression Anastomosis (MCA) has lately been revisited with a focus on minimal invasive surgery (MIS). The aim of this report is to reappraise our earlier experience with MCA with the intention of facilitating future MCA advancement. A retrospective review was conducted regarding preclinical experiments and clinical trials at a single institution from 1980 through 1995. The reviewed information was compiled and appraised to generate proposals for future MCA use. The experimental studies, including 250 MCA cases in gastrointestinal and urinary tract animal models, demonstrated the technical versatility of MCA as well as the superior biomechanical characteristics in comparison to hand-sewn anastomoses. Clinical trials encompassed 87 MCA procedures in 86 children, 2 to 10 years of age, involving the following techniques: non-operative esophageal recanalization (n=15), non-operative ileostomy undiversion (n=46), Swenson pull-through (n=10), non-operative urethral recanalization (n=5), and extravesical ureterocystoneostomy (n=11). Clinical MCA was found to be successful in over 87% of cases. MCA limitations concerning anastomotic failure and scarring were thought to be mostly due to inadequate magnetic compression. Based on our historic experience, we propose further research on the technical aspects of MCA, along with the biologic aspects of anastomotic tissue remodeling. Magnets should be designed and manufactured for a wide spectrum of pediatric surgical indications, particularly in combination with novel MIS techniques.

Postural deficits such as hyperlordosis (hollow back) or hyperkyphosis (hunchback) are relevant health issues. Diagnoses depend on the experience of the examiner and are therefore often subjective and prone to errors. Machine learning (ML) methods in combination with explainable ar-tificial intelligence (XAI) tools have proven useful for providing an objective, data-based orien-tation. However, only a few works have considered posture parameters, leaving the potential of more human-friendly XAI interpretations still untouched. Therefore, the present work proposes an objective, data-driven ML system for medical decision support that enables especially human-friendly interpretations using counterfactual explanations (CFs). Posture data for 1151 subjects were recorded by means of stereophotogrammetry. An expert-based classification of the subjects regarding the presence of hyperlordosis or hyperkyphosis was initially performed. Using a Gaussian progress classifier, the models were trained and interpreted using CFs. Label errors were flagged and re-evaluated using confident learning. Very good classification performances for both hyperlordosis and hyperkyphosis were found, whereby the re-evaluation and correction of the test labels led to a significant improvement (MPRAUC = 0.97). A statistical evaluation showed that the CFs seemed to be plausible in general. In the context of personalized medicine, the present study’s approach could be of importance for reducing diagnostic errors and thereby improving the individual adaptation of therapeutic measures. Likewise, it could be a basis for the development of apps for preventive posture assessment.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

Fifteen transgenic shoot clones (TS A-TS O) regenerated from Hypericum perforatum hairy roots were evaluated for growth characteristics, phenylpropanoid, and naphthodianthrone production, as well as non-enzymatic and enzymatic antioxidant status. Transgenic shoots displayed higher biomass production and non-altered phenotype compared to control shoots. Phenylpropanoid production in TS was not related to phenylalanine ammonia lyase activity indicating that alternative enzymes could be involved in the regulation of phenylpropanoid/flavonoid biosynthesis. The positive correlation between phenylpropanoids (phenolic acids, flavonoids, flavan-3-ols, tannins) and non-enzymatic antioxidant assays suggested that these compounds are the main contributors to the redox state and radical scavenging properties of TS clones. More importantly, enhanced naphthodianthrone production (hypericin, pseudohypericin and protopseudohypericin) in TS was associated with the number of leaf dark glands. Concerning the enzymatic antioxidant status of TS, guaiacol peroxidase was shown as the main enzyme that turn down H2O2 levels, while the up-regulation of superoxide dismutase coincided with decreased O2•− production. The efficiency of antioxidant enzymes for O2•− and H2O2 neutralization declined the MDA level and consequently delayed lipid peroxidation in TS clones. Altogether, H. perforatum transgenic shoots could be proposed as a prospective biotechnological system for scale-up production of naphthodianthrones and phenylpropanoids with antioxidant properties.

The food system represents a key industry for Europe and particularly Germany. However, it is also the single most significant contributor to climate and environmental change. A food system transformation is necessary to overcome the system's major and constantly increasing challenges in the upcoming decades. One possible facilitator for this transformation are radical and disrup-tive innovations that start-ups develop. There are many challenges for start-ups in general and food start-ups in particular. Various support opportunities and resources are crucial to ensure the success of food start-ups. One aim of this study is to identify how the success of start-ups in the food system can be supported and further strengthened by players in the innovation ecosystem in Germany. There is still room for improvement and collaboration toward a thriving innovation ecosystem. A successful innovation ecosystem is characterised by a well-organised, collaborative, and supportive environment with a vivid exchange between the members in the ecosystem. The interviewees confirmed this, and although the different actors are already cooperating, there is still room for improvement. The most common recommendation for improving cooperation is learning from other countries and bringing the best to Germany.

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

Two new Mn(II) and Zn(II) metal-organic compounds of 1,10-phenanthroline and methyl benzoates viz. [Mn(phen)2Cl2]2-ClBzH (1) and [Zn(4-MeBz)2(2-AmPy)2] (2) (where, 4-MeBz = 4-methylbenzoate, 2-AmPy = 2-aminopyridine, phen = 1,10-phenanthroline, 2-ClBzH = 2-chlorobenzoic acid) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FTIR, electronic) and single crystal X-ray diffraction techniques. Crystal structure analysis of the compounds reveals the presence of various non-covalent interactions which provides stability to the crystal structures. Crystal structure analysis of the compound 1 reveals the formation of supramolecular dimer of 2-ClBzH enclathrated within the hexameric host cavity formed by the neighboring monomeric units. Compound 2 is a mononuclear compound of Zn(II) where flexible binding topologies of 4-CH3Bz is observed with the metal centre. Moreover various non-covalent interactions such as lp(O)-π, lp(Cl)-π, C‒H∙∙∙Cl, π-stacking interactions as well as N‒H∙∙∙O, C‒H∙∙∙O and C‒H∙∙∙π hydrogen bonding interactions are found to be involved in plateauing the molecular self-association of the compounds. The remarkable enclathration of the H-bonded 2-ClBzH dimer into a supramolecular cavity formed by two [Mn(phen)2Cl2] complexes has been further studied theoretically using density functional theory (DFT) calculations, non-covalent interaction (NCI) plot index and quantum theory of atoms in molecules (QTAIM) computational tools. Synergistic effects have been also analysed using molecular electrostatic potential (MEP) surface analysis.

To understand microbial growth with mathematical models has a long tradition that dates back to the pioneering work of Jacques Monod in the 1940s. Growth laws are simple mathematical expressions that aim at describing growth rates of microbes as functions of external parameters, in particular nutrient concentrations. These laws are now widely applied to construct, e.g., dynamic ecosystem models. However, to explain the growth laws from underlying (first) principles is extremely challenging. In the second half of the 20th century, numerous experimental approaches aimed at precisely measuring heat production during microbial growth to determine the entropy balance in a growing cell and to quantify the exported entropy. This has led to the development of thermodynamic theories of microbial growth, which have generated fundamental understanding and identified principle limitations of the growth process. Whereas these approaches considered a growing microbe as a black box, modern theories heavily rely on genomic resources to describe and model genome-scale networks to explain microbial growth. Interestingly, however, thermodynamic constraints are often included in modern modelling approaches only in a rather superficial fashion, and it appears that recent modelling approaches and classical theories are disconnected fields. In order to stimulate a closer interaction between these fields, we here review various theoretical approaches that aim at describing microbial growth based on thermodynamic principles. We start with classical black-box models of cellular growth, and continue with genome-scale modelling approaches that include thermodynamics, before we place these models in the context of fundamental considerations based on non-equilibrium statistical mechanics. We conclude by identifying conceptual overlaps between the fields and suggest how the various types of theories and models can be integrated. We outline how concepts from one approach may help to inform or constrain another, and we demonstrate how genome-scale models can be used to infer classical black-box parameters, which are experimentally accessible in growth experiments. Such integration will allow understanding to what extent microbes can be viewed as thermodynamic machines, and how close they operate to theoretical optima.

The accurate prediction of molecular properties such as lipophilicity and aqueous solubility are of great importance and pose challenges in several stages of the drug discovery pipeline. Machine learning methods like graph-based neural networks (GNNs) have shown exceptionally good performance in predicting these properties. In this work, we introduce a novel GNN architecture, called directed edge graph isomorphism network (D-GIN). It is composed of two distinct sub-architectures (D-MPNN, GIN) and achieves an improvement in accuracy over its sub-architectures employing various learning, and featurization strategies. We argue that combining models with different key aspects help make graph neural networks deeper and simultaneously increase their predictive power. Furthermore, we address current limitations in assessment of deep-learning models, namely, comparison of single training run performance metrics, and offer a more robust solution.

This paper deals with the problem of determining the optimal capacity of Concentrated Solar Power (CSP) plants, especially in the context of hybrid solar power plants. This work presents an innovative analytical approach to optimize the capacity of concentrated solar plants. The proposed method is based on the use of additional non-dimensional parameters, in particular the design factor and the solar multiple factor. The paper presents a mathematical optimization model that focuses on the capacity of concentrated solar power plants where thermal storage plays a key role in the energy source. The analytical approach provides a more complete understanding of the design process for hybrid power plants. In addition, the use of additional factors and the combination of the proposed method with existing numerical methods allows for a more refined optimization, which allows for a more accurate selection of the capacity for specific geographical conditions. Importantly, the proposed method significantly increases the speed of computation compared to traditional numerical methods. Finally, the authors present the results of the analysis of the proposed system of equations for calculating the levelized cost of electricity (LCOE) for hybrid solar power plants. The nonlinearity of the LCOE on the main calculation parameters is shown.

Psychological readiness following Anterior Cruciate ligament Reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7±2.5 years old; 174.2±7.5 cm; 70.2±8.5 kg; 18.2±8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°.s-1 and 180°.s-1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls cases showed significantly lower angle-specific quadriceps and hamstrings torque close to extension and lower RTD, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ RTS by focusing on the restoration of RTD and strength at angles close to full knee extension.

Understanding the molecular underpinnings of the evolution of complex (multi-part) systems is a fundamental topic in biology. One unanswered question is the extent to which similar or different genes and regulatory interactions underlie similar complex systems across species. Animal eyes and phototransduction (light detection) are outstanding systems to investigate this question because some of the genetics underlying these traits are well-characterized in model organisms. However, comparative studies using non-model organisms are also necessary to understand the diversity and evolution of these traits. Here, we compare the characteristics of photoreceptor cells, opsins, and phototransduction cascades in diverse taxa, with particular focus on cnidarians. In contrast to the common theme of deep homology, whereby similar traits develop mainly using homologous genes, comparisons of visual systems - especially in non-model organisms - are beginning to highlight a “deep diversity” of underlying components, illustrating how variation can underlie similar complex systems across taxa. Although using candidate genes from model organisms across diversity was a good starting point to understand the evolution of complex systems, unbiased genome-wide comparisons and subsequent functional validation will be necessary to uncover unique genes that comprise complex systems of non-model groups to better understand biodiversity and its evolution.

We discuss what we believe could be an improvement in future discussions of the ever-changing brain. We do so by distinguishing different types of brain variability and outlining methods suitable to analyse them. We argue that, when studying brain and behaviour data, classical methods such as regression analysis and more advanced approaches both aim to decompose the total variance into sensible variance components. In parallel, we argue that a distinction needs to be made between innate and acquired brain variability. For varying high-dimensional brain data, we present methods useful to extract their low-dimensional representations. Finally, to trace potential causes and predict plausible consequences of brain variability, we discuss how to combine statistical principles and neurobiological insights to make associative, explanatory, predictive, and causal enquires; but cautions are needed to raise association- or prediction-based neurobiological findings to causal claims.

Barley straw was used to reinforce PHB in a discontinuous semi-industrial process. Four different fibres were used as reinforcing material : sawdust (SW), defibred (DFBF), delignified (DBF) and bleached (BBF) fibres. Looking at the mechanical properties, onlythe elastic moduli (Et) revealed an improvement. Oppositely, the strengths at break, under both tensile and bending assays, tended to decrease, evidencing a poor affinity between both components. Thanks to the mechani-cal treatment applied on the fibre, DFBF appeared as the most promising filler with the mechani-cal properties of the composites closest to those of neat PHB. DFBF-based composites were then produced by means of a process intensification using a twin-screw extruder, and then moulded into flowerpots. Mechanical results showed almost the same properties between the discontinuous and intensification processes. The suitability of the material to be used on agriculture flowerpots was demonstrated by simulation. . PHB-DFBF composite material can be considered an alterna-tive to replace petrol-based products for applications in agriculture and horticulture.

The detection of antibiotic-resistant facultative pathogenic bacteria in surface waters is common in the present day. However, there is limited understanding of the factors that influence the spread and stabilization of resistance in this habitat, particularly regarding the role of biofilms. Despite the perceived differences between sediments, biofilms, and open water, their potential contribution to the long-term maintenance of resistances remains unclear. In this study, we investigated Escherichia coli isolates obtained from the Mur and Drava rivers in Austria. Samples were collected from both the water column and sediment at two locations per river: upstream and downstream of an urban area, including a sewage treatment plant. The iso-lates were subjected to antimicrobial susceptibility testing against 21 antibiotics belonging to seven distinct classes. Additionally, any isolates exhibiting an extended-spectrum beta-lactamase (ESBL) or carbapenemase phenotype were further analyzed for the presence of specific antimi-crobial resistance genes. E. coli isolates obtained from the two rivers exhibited resistance to at least one of the tested anti-biotics, with rates of 25.83% and 23.66% respectively. The most prevalent antimicrobial re-sistances observed were towards ampicillin, amoxicillin-clavulanic acid, tetracycline, and na-lidixic acid. Surprisingly, there was a similar proportion of resistant bacteria observed in both open water and sediment samples, contrary to expectations. The difference in resistance levels between samples collected upstream and downstream of the cities was minimal. Out of the total isolates, 13 E. coli were found to carry ESBL genes with one isolate carrying the gene for KPC-2 carbapenemase. There were no significant differences between the biofilm (sediment) and open water samples in the occurrence of antimicrobial resistance. Even the difference between the samples upstream and downstream of the cities and their wastewater treatment plants was minor. There seems to be no evidence of a large adaptive effect in this analysed biofilm population of E. coli. The un-typical phenotype of the KPC-producing and some of the ESBL-producing E. coli from this study could, however, be an indication that such adaptation effects generally exist in water.

Background: This study assesses the effects of the ‘Radiant’ image enhancement technique on fetal nuchal translucency (NT) measurements during first trimester sonographic ex-ams. Methods: A retrospective analysis of 263 ultrasound images of first trimester midsagittal sections was conducted. NT measurements were obtained using a semi-automatic tool. Statistical methods were applied to compare NT measurements with and without ‘Radi-ant’ enhancement. An in-vitro setup with predefined line distances provided additional data. Results: Incremental increases in NT measurements were observed with varying levels of ‘Radiant’ application: An average increase of 0.19 mm with ‘Radiant min’, 0.24 mm with ‘Radiant mid’ and 0.30 mm with ‘Radiant max.’ The in-vitro results supported these findings, showing consistent effects on line thickness and measurement accuracy, with the smallest mean deviation occurring at the ‘Radiant mid’ setting. Conclusions: ‘Radiant’ image enhancement leads to significant increases in NT measure-ments. To avoid systematic biases in clinical assessments, it is advisable to disable ‘Radi-ant’ during NT measurement procedures. Further studies are necessary to corroborate these findings and to consider updates to the NT reference tables based on this technology.

Measuring the status and trends of biodiversity is critical for making informed decisions about the conservation, management or restoration of species, habitats and ecosystems. Defining the reference state against which status and change are measured is essential. Typically, reference states describe historical conditions, yet historical conditions are challenging to quantify, may be difficult to falsify, and may no longer be an attainable target in a contemporary ecosystem. We have constructed a conceptual framework to help inform thinking and discussion around the philosophical underpinnings of reference states and guide their application. We characterise currently recognised historical reference states and describe them as Pre-Human, Indigenous Cultural, Pre-Intensification and Hybrid-Historical. We extend the conceptual framework to include contemporary reference states as an alternative theoretical perspective. The contemporary reference state framework is a major conceptual shift that focuses on current ecological patterns and identifies areas with higher biodiversity values, regardless of the disturbance history. The specific context for which we design the contemporary conceptual frame is underpinned by an overarching goal—to maximise biodiversity conservation and restoration outcomes in existing ecosystems. The contemporary reference state framework can account for the inherent differences in the diversity of biodiversity values (e.g., species richness, habitat complexity) across spatial scales, communities and ecosystems. In contrast to historical reference states, contemporary references states are measurable and falsifiable. This ‘road map of reference states’ offers perspective needed to define and assess the status and trends in biodiversity and habitats. Our framework for contemporary reference states provides a tractable way for policy-makers and practitioners to navigate biodiversity assessments to maximise conservation and restoration outcomes in contemporary ecosystems. We illustrate how to define a contemporary reference state using an example from south-eastern Australia.

Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.

Knowledge of the interaction between inorganic and organic phosphates with soil minerals is vital for improving the soil P fertility. To achieve an in-depth understanding we combined adsorption experiments and hybrid ab initio molecular dynamics simulations to analyze the adsorption of common phosphates, i.e. orthophosphate (OP), glycerolphosphate (GP) and inositolhexaphosphate (IHP), onto the 100 surface plane of goethite. Experimental adsorption data per mol P-molecule basis fitted to the Freundlich model show the adsorption strength increases in the order GP &lt; OP &lt; IHP, and IHP adsorption being saturated faster followed by GP and OP. Modeling results show that OP and GP form stable monodentate (M) and binuclear bidentate (B) motifs with B being more stable than M, whereas IHP forms stable M and 3M motifs. Interfacial water plays an important role through hydrogen bonds and proton transfers with OP/GP/IHP and goethite. It also controls the binding motifs of phosphates with goethite. Combining both experimental and modeling results, we propose that the B motif dominates for OP, whereas GP forms M and IHP forms a combination of M and 3M motifs. The joint approach plausibly explains why IHP is the predominant organically bound P form in soil. This study could be considered as a preliminary step for further studies for understanding the mechanisms of how microbes and plants overcome the strong IHP–mineral binding to implement the phosphate groups into their metabolism.

Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based in cell lines and murine models. In this review, we will go over the most frequently used preclinical models, from immortalized-cell and primary tumour cultures in monolayer or 3D, to the currently available animal models. We will scrutinize their efficiency in mimicking the molecular and cellular complexity of head and neck squamous cell carcinoma. Finally, the challenges and opportunities of other envisaged putative approaches, as well as the potential of the preclinical models to further develop customized therapies will be discussed.

The ductile behavior of strain hardening cement-based composites (SHCC) under direct tensile load makes them promising solutions for applications where high energy dissipation is needed, such as earthquake, impact by a projectile, or blast. However, the superior tensile ductility of SHCC due to multiple cracking does not necessarily entail compressive and shear ductility. As an effort to characterize the behavior of SHCC under impact compressive and shear loading, relevant to the mentioned high-speed loading scenarios, the paper at hand studies the performance of a SHCC and its constituent cement-based matrices using the split-Hopkinson bar method. For compression experiments, cylindrical specimens with a length-to-diameter ratio (l/d) of 1.6 were used. The selected length of the sample led to similar failure modes under the quasi-static and impact loading conditions, which was necessary for a reliable comparison of the obtained compressive strengths. The impact experiments were performed in a split-Hopkinson pressure bar (SHPB) at a strain rate that reached 110 s-1 at the moment of failure. For shear experiments, a special adapter was developed for a split-Hopkinson tension bar (SHTB). The adapter enabled performing impact shear experiments on planar specimens using the tensile wave generated in the SHTB. Results showed a dynamic increase factor (DIF) of 2.3 and 2.0 for compressive and shear strength of SHCC, respectively. As compared to the non-reinforced constituent matrix, the absolute value of the compressive strength was lower for the SHCC. Contrarily, under shear loading, the SHCC yielded the higher shear strength than the non-reinforced matrix.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

This research delves into a detailed exploration of the thermal decomposition behavior of bio-based polymers, specifically Thermoplastic Starch (TPS) and Poly(lactic acid) (PLA). The study focuses on the impact of three different heating rates under a nitrogen atmosphere, providing comprehensive insights into the thermal stability of these eco-friendly polymers. In particular, the TPS kinetic model is examined, encompassing the decomposition of three distinct fractions. In contrast, PLA exhibits a simplified kinetic behavior requiring only a fraction described by a zero-order model. The kinetic study involves a systematic investigation into the individual contributions of key components within TPS, including starch, glycerin, and polyvinyl alcohol (PVA). This nuanced analysis contributes to a comprehensive understanding of the thermal degradation process of TPS and PLA, enabling the optimization of processing conditions and the prediction of material behavior across varying thermal environments. Furthermore, the incorporation of different starch sources and calcium carbonate additives in TPS enhances our understanding of the polymer's thermal stability, offering insights into potential applications in diverse industries.

Background: By using outcome prediction scores, it is possible to distinguish between good and poor performers with cochlear implants (CI) after CI implantation. The reasons for poor performance, despite good basic conditions, can be manifold. On the one hand, the postoperative fitting may be inadequate; on the other, neurophysiological disease processes may impair speech understanding with a CI. These disease processes are not yet fully understood. In acoustics, it is known that the auditory brainstem responses (ABR) and their latencies and amplitudes allow differential diagnosis based on reference values for normal-hearing individuals. The aim of this study was to provide reference values for electrically evoked brainstem responses (EABRs) in terms of rate-dependent latencies and amplitudes. Methods: 20 experienced adult CI recipients with a predicted and measured good postoperative word recognition score were recruited from the clinic’s patient pool. In the same stimulation mode and intensity we measured latencies and interpeak-latencies of EABRs and electrically evoked compound action potentials (ECAPs). With a defined supra-threshold stimulation intensity above the individual ECAP threshold, we applied stimulation at several rates between 11 and 91 stimuli per second. Results: We found rate dependences for EABR latency t3 and t5 in the order of 0.19 ms and 0.37 ms respectively, while ECAP was not affected by rate. Correspondingly, the interpeak intervalls’ rate dependences for t5-t1, t5-t3 and t3-t1 were of the order of 0.37 ms, 0.18 ms and 0.19 ms. Comparing the EABR amplitudes between the stimulation rates 11/s and 81/s, we found that at 81/s the amplitudes were significantly reduced down: to 73% for A3 and 81% for A5. These rate dependences of latency and amplitude in EABR have characteristics comparable to those of acoustic ABR. Conclusions: These data may serve to provide reference values for EABR and ECAP latencies, interpeak intervals and amplitudes with respect to stimulation rate. Altered response patterns of ECAPs and EABRs to normalised stimulation modes could be used in the future to describe and classify neuropathological processes in a better-differentiated way.

Literature on the use of nutritional supplements (NS) in tennis players is scarce. The objective of the present study was to evaluate NS consumption in a group of men's tennis players who participated in the 2016 Andalusian team championship. A total of 70 questionnaires from 7 different clubs were registered. The questionnaire was previously designed and evaluated through piloting in which the validity of the content, its application, its structure and its presentation were observed. The results showed that 100% of the sample group was in favor of NS consumption within the law, 88.6% claimed to have consumed them at some time and 61.4% presently consume them. The NS most consumed by study participants were sports drinks (69.35%), energy bars (29%), a vitamin complex (19.35%), protein (serum) (17.74%) and creatine (14.51%). A high percentage of NS consumers thought that they had obtained positive results from NS consumption. The percentages and the findings regarding NS consumption in the present study were similar to the contributions made by other studies which evaluated supplementation in athletes, although with some subtle differences.

We focus on macromolecules which are modelled as sequentially growing dual scale-free networks. The dual networks are built by replacing star-like units of the primal treelike scale-free networks through rings, which are then transformed in a small-world manner up to the complete graphs. In this respect, the parameter γ describing the degree distribution in the primal treelike scale-free networks regulates the size of the dual units. The transition towards the networks of complete graphs is controlled by the probability p of adding link between non-neighbouring nodes of the same initial ring. The relaxation dynamics of the polymer networks is studied in the framework of generalized Gaussian structures by using the full eigenvalue spectrum of the Laplacian matrix. The dynamical quantities on which we focus here are the averaged monomer displacement and the mechanical relaxation moduli. For several intermediate values of the parameter’s set (γ, p) we encounter for these dynamical properties regions of constant in-between slope.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

Background: The respiratory syncytial virus infection (RSV) spread has been unusually high during 2022 and increasing trends have been documented We aimed to assess the survival experience of children hospitalized due bronchiolitis by laboratory-confirmed RSV. Methods: A nationwide and retrospective cohort was conducted in Mexico and data from 436 children aged 5 years and younger, with symptoms onset from August 2021 to November 2022, were analyzed. Survivor functions and 95% confidence intervals (CI) were computed by using the Kaplan-Meier method. Results: The survival rates were high, particularly within the first three weeks of admission. The 3-day survival was 99.8% (CI 95% 98.4-99.9%) and went to 98.9% (CI 95% 96.5-99.7%), 97.5% (CI 95% 91.9-99.3%), 86.7% (95% CI 48.2-97.2%), and 69.4% (95% CI 24.2-91.0%) on days 7, 14, 21 and 28 of hospital stay, respectively. We documented 5 fatal outcomes, and the mortality rate was 2.1 per 1,000 person-days. Conclusions: We analyzed a large set of pediatric patients with bronchiolitis by RSV and the presented results contribute to achieving a better understanding of the in-hospital evolution of this disease.

Metabolic Associated Steatohepatitis Liver Disease (MASLD) currently impacts a quarter of the global population and its prevalence is expected to increase in the future. As a result, the incidence of hepatocellular carcinoma associated with MASLD is also on the rise. Notably, hepatocellular carcinoma in this group does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk of hepatocellular carcinoma to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are yet no universally accepted guidelines

COPD is a chronic inflammatory disease characterized by progressive airflow obstruction. Tobacco smoking is the main cause of COPD (COPD-TS), but chronic exposure to biomass smoke (COPD-BS), mainly wood smoke, is the second risk factor; both are considered to cause different phenotypes of COPD. COPD-BS is more eosinophilic than COPD-TS. The objective of the present study was to evaluate the serum level of interleukins involved in eosinophil maturation, recruitment, and survival, and their association with small airway obstruction, measuring cytokines by multiplex test (Bio-Plex) and evaluating the central airway resistance with impulse oscillometry (IOS), comparatively in patients with COPD due to biomass and smoking. The results showed that IL-1ra, IL-2, IL-4, IL-8, IL-9, IL-13, IL-17, and eotaxin were increased in COPD-BS related to COPD-TS. Resistance parameters showed that R5, X5, AX (area reactance), and R5-R20 were significantly higher in COPD-BS than in the COPD-TS group (p < 0.05). R20 was not different between the groups. These data suggest that the cytokines involved in the effect of eosinophils on airway inflammation in COPD-BS were increased compared with COPD-TS, which appears to be related to a predominance of peripheral airway obstruction in patients with COPD-BS more than in COPD-TS

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

The purpose of this research is to determine if the tradeoffs that Kissick proposed among cost containment, quality, and access remain as rigidly interconnected as originally conceived in the contemporary health care context. Although many have relied on the Kissick model to advocate for health policy decisions, to our knowledge, the model has never been empirically tested. Some have called for policy makers to come to terms with the premise of the Kissick model tradeoffs, others have questioned the model given the proliferation of quality enhancing initiatives, automation, and information technology in the health care industry. One wonders whether these evolutionary changes alter or disrupt the originality of the Kissick paradigms themselves. Methods: Structural Equation Modeling (SEM) was used to evaluate the Kissick hypothetical relationships among the unobserved constructs of cost, quality, and access in hospitals for the year 2018. Hospital data were obtained from Definitive Healthcare a subscription site which contains Medicare data as well as non-Medicare data for networks, hospitals, and clinics (final n= 2,766). Results: Reporting significant net effects as defined by our chosen study variables, we find that as quality increases costs increase, as access increases quality increases, and as access increases, costs increase. Policy and Practice Implications: Our findings lend continued relevance to a balanced approach to health care policy reform efforts. Simultaneously bending the health care cost curve, increasing access to care, and advancing quality of care is as challenging now as it was when the Kissick model was originally conceived.

Kratom (Mitragyna speciosa) is a Southeast Asian plant containing various alkaloids which induce pharmacological effects in humans. In Western countries, online vendors sell a variety of different kratom strains which are marketed to have distinct effect profiles. However, as of yet such marketing claims are unsubstantiated, and therefore the current study investigated whether differently colored kratom products can induce unique effects, as self-reported by users. 644 current kratom users were anonymously surveyed to compare the self-reported effects and motivations for using kratom products sold as red, green, and white strains. Most of the survey respondents were customers of the same kratom vendor, the products of which had been assessed for their alkaloid content by an independent laboratory. The survey respondents reported distinct subjective experiences for different kratom strains, in a manner congruent with common marketing descriptions. However, the product analyses revealed no significant cross-strain differences in alkaloid content, suggesting that the reported effect differences might be disproportionally influenced by marketing narratives and anecdotal reports. Future studies should engage a more diverse population and include kratom strains from various vendors. Controlled, blinded experiments could assess whether the reported effect differences stem from a placebo effect or from alternative factors, e.g. minor alkaloids and terpenes.

The design of highly efficient sensitizers is one of the most significant areas in dye-sensitized solar cell (DSSC) research. We have studied a series of benzothiadiazole-based D-π-π-A organic dyes, putting emphasis on the influence of the donor moiety on the DSSC’s efficiency. Using linear response time-dependent density functional theory (TDDFT) with the CAM-B3LYP functional different donor groups were characterized in terms of electronic absorption spectra and key photovoltaic parameters. As a reference a dye has been considered which has a benzothiadiazole fragment linked via thiophene rings to a diphenylamine donor and a cyanoacrylic acid acceptor. The different systems are first studied in terms of individual performance parameters, which are eventually aggregated into the power conversion efficiency. Here only the amino-substituted species shows a modest increase, whereas the dimethylamino case even shows a decrease.

Three-dimensional (3D) facies and petrophysical models were generated from previously published data of carbonate strata in the Dam Formation (eastern Saudi Arabia) to quantitatively investigate, describe, understand, model, and predict the permeability anisotropy of tidal flat carbonate within a sequence stratigraphic framework. The resulting 3D models were used to conduct fluid flow simulations to demonstrate how permeability anisotropy influences the production of hydrocarbons and ultimately affects decisions concerning future drilling in the exploration and development of carbonate reservoirs that have tidal flat strata. The constructed 3D facies model consists of four lithofacies associations, two of which were grain-dominated associations and two of which were mud-dominated associations. These lithofacies associations varied spatially in four reservoir zones (zones 1 to 4), which represent two fourth-order sequences in the uppermost part of the Dam Formation. Zones 1 and 3 consist of transgressive parasequences, and zones 2 and 4 consist of the regressive parasequences of these sequences. The 3D porosity and permeability models have a coherent match with the distribution of the lithofacies and the stratigraphic framework of the Dam Formation. The results suggested that the permeability anisotropy in zones 1 and 3 is controlled by the occurrence of the grain-dominated lithofacies associated with tidal flat channels. This lithofacies association overlies the sequence boundaries of sequences 1 and 3, forms reservoir bodies with relatively high permeability values, and is elongated perpendicular to the shoreline of the depositional environments. In contrast, permeability anisotropy in zones 2 and 4 is thought to be controlled by the occurrence of the grain-dominated lithofacies associated with the oolitic shoal. This lithofacies association overlies the maximum flooding surface of sequences 2 and 4, forms reservoir bodies with relatively high permeability values, and is elongated parallel to the shoreline of the depositional environments. Fluid flow simulation results suggested that the trend in hydrocarbon production from the constructed 3D models depends on permeability anisotropy in each reservoir zone. Thus, recognizing trends in permeability anisotropy, which might be predicted using sequences stratigraphy, could help to identify potential areas for future drilling.

Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of a tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue derived stem cell-conditioned medium. Expression of proapoptotic genes was upregulated, expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7.

G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. 3D pharmacophore models are powerful computational tools in silico drug discovery, presenting myriad opportunities for the integration of GPCR structural biology and cheminformatics. This review highlights success stories in the application of 3D pharmacophore modeling to de novo drug design, discovery of biased and allosteric ligands, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, mechanistic understanding of GPCR pharmacology and elucidation of ligand-receptor interactions. Furthermore, advances in the incorporation of dynamics and machine learning will be highlighted. The review will analyze challenges in the field of GPCR drug discovery, detailing how 3D pharmacophore modeling can be used to address them. Finally, we will present opportunities afforded by 3D pharmacophore modeling in the advancement of our understanding and targeting of GPCRs.

Recently, the Hypervolume Newton method (HVN) has been proposed as fast and precise indicator-based method for solving unconstrained bi-objective optimization problems with objective functions that are at least twice continuously differentiable. The HVN is defined on the space of (vectorized) fixed cardinality sets of decision space vectors for a given multi-objective optimization problem (MOP) and seeks to maximize the hypervolume indicator adopting the Newton-Raphson method for deterministic numerical optimization. To extend its scope to non-convex optimization problems the HVN method was hybridized with a multi-objective evolutionary algorithm (MOEA), which resulted in a competitive solver for continuous unconstrained bi-objective optimization problems. In this paper, we extend the HVN to constrained MOPs with in principle any number of objectives. We demonstrate the applicability of the extended HVN on a set of challenging benchmark problems and show that the new method can be readily be applied to solve equality constraints with a high precision problems, and to some extend also inequalities. We finally use HVN as local search engine within a MOEA and show the benefit of this hybrid method on several benchmark problems.

Extracellular vesicles (EVs) can transfer diverse RNA cargo for intercellular signalling. EV-associated RNAs have been found in diverse fungi and were proposed to be relevant for pathogenesis in animal hosts. In plant-pathogen interactions, small RNAs are exchanged in a cross-kingdom RNAi warfare and EVs were considered to be a delivery mechanism. To extend the search for EV-associated molecules involved in plants-pathogen communication, we have characterised the repertoire of EV-associated mRNAs secreted by the maize smut pathogen, Ustilago maydis. For this initial survey, EVs were isolated from axenic filamentous cultures that mimic infectious hyphae. The EV-associated RNAs were resistant to degradation by RNases and the presence of intact mRNAs was evident. The set of mRNAs enriched inside EVs relative to the fungal cells are functionally distinct from those that are depleted from EVs, particularly overrepresented in metabolic enzyme activities. Intriguingly, mRNAs of some known effectors and other proteins linked to virulence were found in EVs. Furthermore, several mRNAs enriched in EVs are also upregulated during infection, suggesting that EV-associated mRNAs may participate in plant-pathogen interaction.

Atrophy quantification is fundamental for understanding brain development and diagnosing and monitoring brain diseases. FSL-SIENA is a well-known fully-automated method that has been widely used in brain magnetic resonance imaging studies. However, intensity variations arising during image acquisition that may compromise evaluation, analysis and even diagnosis. In this work, we study whether intensity standardisation can improve longitudinal atrophy quantification. We considered seven methods comprising z-score, fuzzy c-means, Gaussian mixture model, kernel density, histogram matching, white stripe, and removal of artificial voxel effects by linear regression (RAVEL). We used a total of 330 scans from two publicly-available datasets, ADNI and OASIS. In scan-rescan assessments, that measures robustness to subtle imaging variations, intensity standardisation did not compromise the robustness of FSL-SIENA significantly (p>0.1). In power analysis assessments, that measures the ability to discern between two groups of subjects, three methods led to consistent improvements in both datasets with respect to the original: fuzzy c-means, Gaussian mixture model, and kernel density estimation. Reduction in sample size using these three methods ranged from 17% to 95%. The performance of the other four methods was affected by spatial normalisation, skull stripping errors, presence of periventricular white matter hyperintensities, or tissue proportion variations over time. Our work evinces the relevance of appropriate intensity standardisation in longitudinal cerebral atrophy assessments using FSL-SIENA.

The pennate diatom Phaeodactylum tricornutum is a model organism able to synthesize industrially-relevant molecules. Commercial-scale cultivation currently requires large monocultures, prone to bio-contamination. However, little is known about the identity of the invading organisms. To reduce the complexity of natural systems, we systematically investigated the microbiome of non-axenic P. tricornutum cultures from a culture collection in reproducible experiments. The results revealed a dynamic bacterial community that developed differently in “complete” and “minimal” media conditions. In complete media, we observed an accelerated “culture crash”, indicating a more stable culture in minimal media. The identification of only four bacterial families as major players within the microbiome suggests specific roles depending on environmental conditions. From our results we propose a network of putative interactions between P. tricornutum and these main bacterial factions. We demonstrate that, even with rather sparse data, a mathematical model can be reconstructed that qualitatively reproduces the observed population dynamics, thus indicating that our hypotheses regarding the molecular interactions are in agreement with experimental data. Whereas the model in its current state is only qualitative, we argue that it serves as a starting point to develop quantitative and predictive mathematical models, which may guide experimental efforts to synthetically construct and monitor stable communities required for robust upscaling strategies.

Electric mobility begins to enter East-African markets. This paper aims to investigate what policy level solutions and stakeholder constellations are established in the context of e-mobility in Dar es Salaam, Kigali, Kisumu and Nairobi and in which ways they attempt to tackle implementation of electric mobility solutions. The study employs two key methods including content analysis of policy and programmatic documents as well as interviews based on purposive sampling ap-proach with stakeholders involved in mobility transitions. The study findings point out that transport operators and their representative associations are less recognized as major players in the transition, far behind new e-mobility players (start-ups) and public authorities. The study further indicates that a set of financial and technical barriers persist such as high upfront invest-ment costs in vehicles and infrastructure, or anxieties regarding competitiveness with fossil fuel vehicles, that constrain the uptake of such private e-mobility initiatives. This study concludes by identifying current gaps that need to be tackled by policy makers and stakeholders in order to implement inclusive electric mobility in East-African cities, considering modalities that include transport providers and address their financial constraints.

Among extensive studies on click chemistry the inverse electron-demand Diels-Alder reaction between 1,2,4,5-tetrazine (Tz) and trans-cyclooct-2-en (TCO) has gained increasing attraction due to its exceptionally fast reaction kinetics and high selectivity for in vivo pretargeting applications including PET imaging. The facile two-step approach utilizing TCO-modified antibodies as targeting structures has not made it into clinic though as the increase in blood volume from mice to human seems to be the major limitation. This study aimed to show if the design of multimeric Tz-ligands by chelator scaffolding can improve the binding capacity and may lead to enhanced PET imaging with gallium-68. For this purpose we utilized the macrocyclic siderophore Fusarinine C (FSC) which allows to conjugate up to three Tz-residues due to three primary amines available for site specific modification. The resulting mono- di- and trimeric conjugates were radiolabelled with gallium-68 and characterized in vitro (logD, protein binding, stability, binding towards TCO modified rituximab (RTX)) and in vivo (biodistribution- and imaging studies in normal BALB/c mice using a simplified RTX-TCO tumour surrogate). The 68Ga-labelled FSC-based Tz-ligands showed suitable hydrophilicity, high stability, high targeting specificity and the binding capacity to RTX-TCO was increased by the grade of multimerization. Corresponding in vivo studies showed a multimerization typical profile but generally suitable pharmacokinetics with low accumulation in non-targeted tissue. Imaging studies in RTX-TCO tumour surrogate bearing BALB/c mice confirmed this trend and revealed improved targeting by multimerization as increased accumulation in RTX-TCO positive tissue was observed.

Tetanus toxoid (TT) vaccination during pregnancy has been proven as an effective preven-tive measure to reduce the incidence of maternal and neonatal morbidity and mortality worldwide. This study aimed to assess the determinants of TT vaccine uptake among pregnant women in two public maternity specialized hospitals in Sudan. A hospi-tal-based cross-sectional study was conducted in two public hospitals, Omdurman Ma-ternity and AL-Saudi hospitals in Omdurman, Khartoum State in Sudan, from February to April 2020. Logistic regression analysis was carried out to identify factors associated with receiving three or more doses of TT vaccine among pregnant women (protected against tetanus), presented as Odds ratios, with p-values <0.05 considered significant (at 95% confidence interval). The study recruited 350 pregnant women, with 313 participants in-cluded in the analysis. This study found that only 40% of the pregnant women received 3 doses or more (protected) of TT vaccine during their current pregnancy. Pregnant women who attended Al Saudi hospital were less likely to be protected against Tetanus (received ≥ 3 doses) compared to those who attended Omdurman hospital [OR= 0.49 (95%C.I 0.29-0.82), p-value <0.05]. Furthermore, the number of children at home was a significant predictor of mothers’ immunization status as those with five children or more were ten times more to be protected against tetanus [OR= 10.54 (95% C.I 4.30-25.86), p-value <0.05]. We conclude that this low rate of TT vaccine uptake found in this study among pregnant women increases the number of newborn babies susceptible to contracting neonatal tetanus. This study provides useful information that can inform the will increase in the probabilities of morbidities and mortalities that result from maternal and neonatal tetanus. The findings of this study should be considered in development of communication strategies targeting and prioritizing at-risk groups to increase TT vaccine uptake among pregnant women in Sudan.

This research work investigates the possibility of shielding gravity. The ultimate purpose of this work is to understand the reality behind the concept of Gravitational Shielding (GS) and time dilation. Since the 19th century, scientists have tried to arrive at an understanding of GS via the use of various experiments. Unfortunately, some experiments failed to prove the existence of gravitational shielding, whereas some results proclaimed the possibility of attaining GS. The original phenomenon exhibited by nature cannot easily be understood, but some experiments have demonstrated that the answer may lie behind the mysterious GS. If GS is proved, then in the future, it would be possible to travel across black holes by defying gravity or through any bigger mass having high gravitational field. To unravel the mystery of GS, this work investigates the history of GS and considers the future vision of technologically advanced spacecraft or other warp drive mechanisms with appropriate gravitational shielding. Though the problem is very complex, this research work tries to come to a deeper understanding and explanation of the complexity involved in achieving gravitational shielding.

From 2020 to 2023 many people around the world were forced to wear masks for large proportions of the day based on mandates and laws. We aimed to study the potential of face masks for the content and release of inanimate toxins. A scoping review of 1003 studies was performed (database search in PubMed/MEDLINE, qualitative and quantitative evaluation). Twenty-four studies were included (experimental time 17 min to 15 days) evaluating content and/or release in 631 masks (273 surgical, 228 textile and 130 N95 masks). Most studies (63%) showed alarming results with high micro- and nanoplastics (MPs and NPs) release and exceedances could also be evidenced for volatile organic compounds (VOCs), xylene, acrolein, per-/polyfluoroalkyl substances (PFAS), phthalates (including di(2-ethylhexyl)-phthalate, DEHP) and for Pb, Cd, Co, Cu, Sb and TiO₂. Of course, masks filter bacteria, dirt and plastic particles and fibers from the air we breathe and have specific indications, but according to our data they also carry risks. Depending on the application, a risk-benefit analysis is necessary. However, mask mandates during the SARS-CoV-2 pandemic have been generating an additional source of potentially harmful exposition to toxins at population level with almost zero distance to the airways.

Presentation of case: A 20 year old men from Simanjiro district in northern Tanzania presented with a 3 year history of splenomegaly, fatigue, cachexia, skin maculae and recent onset of watery diarrhea at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. Due to laboratory findings of pancytopenia, diagnostic workup included bone marrow aspiration cytology and biopsy. Although the rapid test (IT LEISH, rK39 RDT) was negative, blood smear showed amastigote forms of Leishmaniasis in macrophages. Repeat bone marrow aspiration and PCR eventually confirmed VL. The patient denied travel to known endemic areas of visceral leishmaniasis (VL). Treatment was initiated with Amphotericin B, but the patient died on the fourth day of treatment from respiratory insufficiency. An autopsy revealed massive organ manifestations of VL. Case discussion: This is the first reported autochthonous case of VL in Tanzania. Clark et al. detected the vector Phlebotomous martini in Northern Tanzania in 2013, in a region boardering the district of our patient. The negative rapid test draws attention to the fact that sensitivity and specificity was found to be low in East African VL patients as displayed earlier by a Kenyan study. Therefore, tissue samples (spleen or bone marrow) remain necessary for diagnosis. The variety of symptoms in this presented case was remarkable, including the occurrence of Post Kala Azar Dermal Leishmaniasis (PKDL) and VL at the same time. This has been described in East African VL cases before as well as the occurrence of chronic diarrhea. An elongated undiagnosed period likely led to a mixed clinical picture that included: hepato-splenomegaly, PKDL, cachexia, and diarrhea.

We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis was conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p>0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo.