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.

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.

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.

Background: Night-migratory birds sense the Earth´s magnetic field by an unknown molecular mechanism. Theoretical and experimental evidence support the hypothesis that light-induced formation of a radical-pair in European robin cryptochrome 4a, ErCry4a, is the primary signalling step in the retina of the bird. In the present work, we investigated a possible route of cryptochrome signalling involving the α-subunit of the cone specific heterotrimeric G protein from European robin. Methods: Protein-protein interaction studies include surface plasmon resonance, pulldown affinity binding and Förster resonance energy transfer. Results: Surface plasmon resonance studies showed direct interaction revealing high to moderate affinity for binding of non-myristoylated and myristoylated G protein to ErCry4a, respectively. Pulldown affinity experiments confirmed this complex formation in solution. We validated these in vitro data by monitoring the interaction between ErCry4a and G protein in a transiently transfected neuroretinal cell line using Förster resonance energy transfer. Conclusions: Our results suggest that ErCry4a and the G protein also interact in vivo and might constitute the first biochemical signalling step in radical-pair-based magnetoreception.

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.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

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.

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.

In a generalized topological space Tg = (Ω, Tg), ordinary interior and ordinary closure operators intg, clg : P (Ω) −→ P (Ω), respectively, are defined in terms of ordinary sets. In order to let these operators be as general and unified a manner as possible, and so to prove as many generalized forms of some of the most important theorems in generalized topological spaces as possible, thereby attaining desirable and interesting results, the present au- thors have defined the notions of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in terms of a new class of generalized sets which they studied earlier and studied their essen- tial properties and commutativity. The outstanding result to which the study has led to is: g-Intg : P (Ω) −→ P (Ω) is finer (or, larger, stronger) than intg : P (Ω) −→ P (Ω) and g-Clg : P (Ω) −→ P (Ω) is coarser (or, smal ler, weaker) than clg : P (Ω) −→ P (Ω). The elements supporting this fact are reported therein as a source of inspiration for more generalized operations.

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).

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

In a generalized topological space T_g = (Ω, T_g) (T_g-space), the g-topology T_g : P (Ω) −→ P (Ω) can be characterized in the generalized sense by specifying the generalized open, generalized closed sets (g-T_g-open, g-T_g-closed sets), generalized interior, generalized closure operators g-Intg, g-Cl_g : P (Ω) −→ P (Ω) (g-T_g-interior, g-T_g-closure operators), or generalized derived, generalized coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω) (g-T_g-derived, g-T_g-coderived operators), respectively. For very many T_g-spaces, the δ^th-iterates g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω) of g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, defined by transfinite recursion on the class of successor ordinals are also themselves g-T_g-derived, g-T_g-coderived operators for new g-topologies in the generalized sense on Ω. Thus, the use of novel definitions of g-T_g-derived, g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, based on a very clever construction, together with their δ^th-iterates g-T_g-operators g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω), defined by transfinite recursion on the class of successor ordinals, will give rise to novel generalized g-topologies on Ω. The present authors have been actively engaged in the study of g-T_g-operators in T_g-spaces. The study of the essential properties and the commutativity of novel definitions of g-T_g-interior and g-T_g-closure operators g-Int_g, g-Cl_g : P (Ω) −→ P (Ω), respectively, in T_g has formed the first part, and the study of the essential properties and sets of consistent, independent axioms of novel definitions of g-T_g-exterior and g-T_g-frontier operators g-Ext_g, g-Fr_g : P (Ω) −→ P (Ω), respectively, has formed the second part. In this work, which forms the last part on the theory of g-T_g-operators in T_g-spaces, the present authors propose to present novel definitions and the study of the essential properties of g-T_g-derived and g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, and their δ^th-iterates, and the notions of g-T_g-open and g-T_g-closed sets of ranks δ in T_g-spaces.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

In a generalized topological space Tg = (Ω, Tg), generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, are merely two of a number of generalized primitive operators which may be employed to topologize the underlying set Ω in the generalized sense. Generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, are other generalized primitive operators by means of which characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) can be given without even realizing generalized interior and generalized closure operations first in order to topologize Ω in the generalized sense. In a recent work, the present authors have defined novel types of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in Tg and studied their essential properties and commutativity. In this work, they propose to present novel definitions of generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, a set of consistent, independent axioms after studying their essential properties, and established further characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) in Tg.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

Visual Patient technology is a situation awareness–oriented visualization technology that translates numerical and waveform patient monitoring data into a new user-centered visual language. Vital sign values are converted into colors, shapes, and rhythmic movements—a language humans can easily perceive and interpret—on a patient avatar model in real time. In this review, we summarize the current state of the research on the Visual Patient, including the technology, its history, and its scientific context. We also provide a summary of our primary research and a brief overview of research work on similar user-centered visualizations in medicine. In several computer-based studies under various experimental conditions, Visual Patient transferred more information per unit time, increased perceived diagnostic certainty, and lowered perceived workload. Eye tracking showed the technology worked because of the way it synthesizes and transforms vital sign information into new and logical forms corresponding to the real phenomena. The technology could be particularly useful for improving situation awareness in settings with high cognitive demand or when users must make quick decisions. This comprehensive review of Visual Patient research is the foundation for an evaluation of the technology in clinical applications, starting with a high-fidelity simulation study in early 2020.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

：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.

Increased demand for wearing face masks, lack of surgical masks and N95 respirators during the coronavirus pandemic created alternative needs for cloth masks. Therefore, to determine filtration efficacy, reusability and duration of wearing new and hand washed cloth masks, the bacteria filtration efficacy was tested using Staphylococcus aureus and Escherichia coli. Cotton cloth masks; single layer without pleats and with pleats, double layer with canvas filter in the middle, double layer with stiff filter in the middle, double layer with pleats on both sides and locally made and imported surgical masks and N95 respirators were used. Bacterial suspension was sprayed over outer surface and swabbed from inner surface at 0hrs, 4thhr, 8thhr and 12thhr. Similar procedure was performed to hand washed and ironed cotton cloth masks. After 24 hours of incubation, single layer without pleats and with pleats had no filtration efficacy(0-100%). Double layer with stiff filter in the middle and double layer with pleats on both sides had higher filtration efficacy(99.96-100%), this filtration efficacy remained up to three occasions of hand washing with soap and water, conferring protection up to 12hours. Filtration efficacy of surgical masks made locally, imported and N95 respirators were 90-100%, 99.99-100%, and 99.99-100% respectively.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

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.

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.

BackgroundLiving donor liver transplantation offers comparable long-term results to cadaveric donor transplantation. This study analyzes the selection process of living liver donors at a Western transplant center that utilizes both donation forms. MethodsThis retrospective analysis examined potential living donors, collecting medical data and reasons for refusal, and divided patients by indication and urgency for transplantation. ResultsFrom January 2013 to December 2023, 594 potential living donors were assessed at Jena University Hospital. Of these, 124 living donor transplants were performed. During outpatient evaluation, 357 potential donors were excluded. Subsequently, 238 individuals underwent inpatient assessment, with 100 more being excluded. Main reasons for donor refusal included medical or psychological issues (n=160), disease progression in recipients (n=90), and recipient refusal or donor withdrawal (n=54). The evaluation process showed a trend towards considering more distant relatives and acquaintances as donor candidates with increasing severity of the recipient's disease.

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.

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.

Several specific types of generalized compactness of generalized topological spaces have been defined, investigated and related to compactness in ordinary topological spaces from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized compactness in a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of ordinary and generalized connectedness in a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new type of generalized connectedness in a generalized topological space is reported herein as a starting point for more generalized types.

Several specific types of generalized maps of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized maps of a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of generalized sets of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized sets of a generalized topological space is reported herein as a starting point for more generalized classes.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

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.

In this study we have investigated the effect of the addition of Nb2O5 (up to 5 mol%) on the structure and luminescent properties of ZnO-B2O3 glass doped with 0.5 mol % Eu2O3 by using of infrared (IR), Raman and photoluminescence (PL) spectroscopy. Physical properties as molar volume, oxygen packing density and glass transition temperature were determined using the results of differential thermal analyisis (DTA) and Archimedes principle for density. IR and Raman spectra revealed that niobium ions incorporate into the base zinc borate glass as NbO4 trtraherda and NbO6 octahedra. A strong red emission from the 5D0 level of Eu3+ ions was registered under near UV (392 nm) excitation using the sharp 7F0 - 5L6 transition of Eu3+. The integrated fluorescence intensity ratio R (5D0 → 7F2/5D0 → 7F1) was calculated to estimate the degree of asymmetry around the active ion, suggesting a location of Eu3+ in non-centrosymmetric sites. The higher Еu3+ luminescence emission observed in zinc borate glasses containing 1÷5 mol% Nb2O5 compared to the Nb2O5-free zinc borate glass evidences that Nb2O5 is suitable component for modification of host glass structure and improving the emission intensity.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

Several specific types of ordinary and generalized separation axioms of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized separation axioms of a generalized topological space is reported herein as a starting point for more generalized classes.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Mercury has a strong environmental impact since both its organic and inorganic forms are toxic and it represents a pollutant of global concern. Liquid Hg is highly volatile and it can be released during natural and anthropogenic processes in the hydrosphere, biosphere and atmosphere. In this study the distribution of Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations on paints, plasters, roof tiles, concretes, metals, dust and wood structures were determined in the main buildings and structures of the former Hg-mining area of Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into 7 units) covers a surface of about 65 ha and contains mining structures and managers and workers buildings. In this work, nine surveys of GEM measurements were carried out from July 2011 to August 2015 for the buildings and structures located in the units 2, 3 and 6. Moreover, detailed measurements were performed in February, April, July, September and December 2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a strong variability in terms of space and time mostly depending on the distance from the building hosting driers, furnaces and condensers and ambient temperature, respectively. In the Unit 2 surveys carried out in the hotter period (from June to September) showed GEM concentrations up to 27,500 ng m⁻³, while in the Unit 6 they were on average much higher and occasionally they saturated the GEM measurement device (>50,000 ng m⁻³). Concentrations of total (in mg kg⁻¹) and leached (in μg L⁻¹) mercury measured in different building materials (up to 46,580 mg kg⁻¹ and 4,470 mg L⁻¹ for total and leached mercury, respectively) showed for the same type of material highly variable values in dependence on the edifice or mining structure from which they were collected. The results obtained in this study are of relevant interest for the operational cleanings to be carried out during the reclamation activities.

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.

By combining general relativity and CPT symmetry, the theory of CPT gravity predicts gravitational repulsion between matter and CPT-transformed matter, i.e. antimatter inhabiting an inverted space-time. Such repulsive gravity turned out to be an excellent candidate for explaining the accelerated expansion of the Universe, without the need for dark energy. The recent results of the ALPHA-g experiment, which show gravitational attraction between antihydrogen atoms and the Earth, seem to undermine this success in the cosmological field. Analyzing the above theory, we find two solutions that can be consistent with the experimental results, while preserving the large-scale gravitational repulsion. The first highlights how repulsive gravity can be the result of the interaction with an inverted space-time, but occupied by matter and not antimatter, and therefore the antimatter present in our space-time has no reason to exhibit gravitational repulsion. The second retains the original CPT transformation, resulting in repulsive gravity between matter and antimatter, but with the caveat that antimatter immersed in our space-time cannot exhibit the PT transformation which is the cause of the repulsion. Finally, it is shown that, in a Newtonian approximation of the geodesic equation, time reversal is not a necessary operation for repulsive gravity, therefore opening the possibility of an expanding cosmos with a single time direction.

The spin magnetic moments and spin g factors (g_s = -2) of electron, muon and tau are explained based on the electric charges (EC) and lepton charges (LC) in terms of the three-dimensional quantized space model. The spin g factors of electron, muon and tau are g_s = -2 which is the sum of the EC g factor (g_EC = -1) and the LC g factor (g_LC = -1). The spin g factor (g_s = -2) of the electron is predicted by the Dirac’s equation. The orbit g factors of electron, muon and tau are g_L = g_EC = -1 from the EC g factor (g_EC = -1) without the contribution of the LC g factor (g_LC = -1). The spin g factors of the elementary fermions are calculated from the equation of g_s = g_EC + g_LC + g_CC where g_EC = EC/|EC|, g_LC = LC/|LC| and g_CC = CC/|CC|. For example, the spin g factors of the neutrinos and dark matters are g_s = -1. The spin g factors of the u and d quarks are g_s = 0 and g_s = -2, respectively. The g factor problem of neutrinos with the non-zero LC charges are solved by the LC Coulomb force of F_c(LC) ≈0. It is, for the first time, proposed that the binary motion (fluctuations) of the m_EC and m_LC masses for the electron, muon and tau leptons make the anomalous g factor. This binary motion could be originated from the virtual particle processes including the photons. Also, the weak force (beta) decay is closely related to the binary motion of the m_EC and m_LC for the electron, muon and tau leptons.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

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.

Mobile robots need an environmental perception ability in order to interact with the surrounding environment. In this paper we present the G-SLAM method, where the map is consisted of a cloud of scattered points in the continuous space and each point is accompanied by an obstacle existence probability. On the other hand the robot's pose (and trajectory) is estimated by an particle filters while the cloud of points is estimated by an adaptive recursive algorithm which is presented. Main feature of the presented method is the adaptive repositioning of the scattered points and their convergence around obstacles. In addition to our previous publications, In this paper a mathematical derivation of the method is presented and real case scenarios are discussed, presented and compared with other methods.

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.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

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.

In this study, 10%PTFE/PEEK blend were modified by potassium titanate whisker (PTW) and chopped glass fiber (GF), respectively. The blends were prepared by three-screw extruder. Through the investigation of thermal stability, tribological properties, mechanical properties and rheological behavior, the effects of reinforcing agents were determined. The results illustrated that the mechanical properties of 10%PTFE/PEEK blend can be dramatically improved by adding reinforcing agent of PTW or GF, and the reinforcing effect of GF was especially obvious. As for tribological properties, 1% addition was the best proportion. The friction coefficient and wear rate of the blend with 1% PTW were 0.283 and 4.97 × 10^-6 mm³/N · m, which decreased by 7.2% and 21% compared with those of the blend without reinforcing agent.

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.

In this paper, we investigate some kind of Dynkin game under $g$-expectation induced by backward stochastic differential equation (shortly for BSDE). We define the lower and upper value functions $\underline{V}_t=ess\sup\limits_{\tau\in{\mathcal{T}_t}} ess\inf\limits_{\sigma\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$ and $\overline{V}_t=ess\inf\limits_{\sigma\in{\mathcal{T}_t}}ess\sup\limits_{\tau\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$, respectively. Under some regular assumptions, a pair of saddle point is obtained and the value function of Dynkin game $V(t)=\underline{V}_t=\overline{V}_t$ follows. Furthermore, the constrained case of Dynkin game is also considered.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

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.

Analyses of the three predominant types of sedimentation – clastic, carbonate and black shale – revealed their discontinuity/continuity in different facies environments of the Middle and Late Devonian of the central part of the Volga-Urals petroleum province, namely (1) in depressions, both condensed and non-condensed, (2) on the slopes of depressions and (3) in shallow water environments represented by tectonic arches or localised biohermal uplifts. The regional zonation of conodonts, correlated with the global chronostratigraphic scheme, substantiates the stratigraphic completeness of the general Devonian sequence in this area. In particular, the sedimentation of organic-rich black shales, traditionally considered as source rocks, lasted more than 29 million years, starting from the Late Eifel and ending at the Devonian-Carboniferous boundary. There was only one hiatus in the deposition of both black shales and carbonate sediments, lasting about 2.5 million years at the end of the Frasnian. That interval is dominated by clastic sediments, which are considered to be the most productive reservoirs of the Volga-Ural province. In the time interval from the beginning of the Eifel to the end of the Frasnian (about 17 Ma), (a) clastic sediments show the highest accumulation rates; (b) the most complete sequences occur in depressions; and (c) arches and uplifts show the most significant gaps in the geological record. During Famennian, (a) clastic sedimentation has completely ceased; (b) differences between the slopes of troughs and shallow-water environments have diminished, resulting in stable accumulation of carbonate sediments in both settings; (c) the decrease in sequence thickness (up to 50 m) in depressions suggests reduced accumulation rates of deep-water organic-rich black shales. The results help to understand the complex spatial relationship between different coexisting sedimentation types and focus attention to the incompleteness of the geological record in different environments.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

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.

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.

Generally, stochastic functional differential equations (SFDEs) pose a challenge as they often lack explicit exact solutions. Consequently, it becomes necessary to seek certain favorable conditions under which numerical solutions can converge towards the exact solutions. This article aims to delve into the convergence analysis of solutions for stochastic functional differential equations by employing the framework of G-Brownian motion. To establish the goal, we find a set of useful monotone type conditions and work within the space Cr((−∞,0];Rn). The investigation conducted in this article confirms the mean square boundedness of solutions. Furthermore, this study enables us to compute both LG2 and exponential estimates.

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

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.

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.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

The present paper reports an exact approach quantifying the electromagnetic contribution to the anomalous magnetic moment occurring in isolated system comprised of non-composite particle carrying elementary electric charge. Essential averaging procedure and regularization of the electromagnetic field potentials necessary when quantifying the electromagnetic self-interactions and when deriving equations of motion without singularities and obeying the conservation laws are thoroughly discussed. The study shows that the dynamics of the considered system is associated to unique classical transcendental equations of motion satisfied by the particle's velocity and the electromagnetic contribution to the anomalous $g$-factor known from the quantum electrodynamics. The equations of motion lead to an exact analytical expression for the anomalous $g$-factor that provides more accurate result than that calculated with the aid of quantum electrodynamics. It matches the experimentally measured value reported in the literature to a one part per trillion. We obtain a_e=0.00115965218000(65) thus reveling the potential of non-perturbative, non-probability methods in predicting the electron's anomalous g-factor.

G-quadruplex, a unique secondary structure in nucleic acids found throughout human genome elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, G-quadruplex structure regulates transcription, translation, splicing, telomere stability etc. Changes in its structure and stability lead to differential expression of oncogenes causing cancer. Thus, targeting G-Quadruplex structures with small molecules/ other biologics has shown elevated research interest. Covering previous reports, in this review we try to enlighten the facts on the structural diversity in G-quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next generation cancer treatment.

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.

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.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

In this article/review, the selective interactions of several berberine and palmatine derivatives with various DNA G-quadruplex structures are reported. These derivatives were constructed starting from two natural compounds, berberine and palamatine, through specific synthetic passages following two different schemes for each of them and using several substituents. The details of these synthesis are also described. Indeed, the study of the interactions of these derivative compounds with various G-quadruplex forming sequences was carried out by means of various structural and biochemical techniques. The results show that the presence of suitable side chains are very useful to improve the interaction of the ligands with G-quadruplex structures. Thus, since G-quadruplex formation is promoted by these compounds, which have never been reported before, these may be tested as potential anticancer drugs.

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.

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.

In the bioprinting process, controlling the motion of bioprinters involves a computer-aided design (CAD) model, converting that model into g-code, and transmitting the motion commands to the bioprinters. The g-code file contains information about the motion of the axes and can be generated using various software. However, a challenge arises when using g-code between different bioprinters. Therefore, the objective of this study was to propose a reliable method for analyzing the differences in 3D bioprinting devices by parameterizing a crucial variable for extrusion bioprinting: the E-value. Four bioprinters from three different manufacturers were used to investigate the extrusion behavior when subjected to the same E-value.

The G-NUMEN array is the future gamma spectrometer of the NUMEN experiment (Nuclear Matrix Element for the Neutrinoless double beta decay), to be installed around the object point of the MAGNEX magnetic spectrometer at the INFN-LNS laboratory.. This project aims at exploring Double Charge Exchange (DCE) reactions in order to obtain crucial information about the neutrinoless double beta decay (0νββ). The primary objective of the G-NUMEN array is to detect the gamma rays emitted from the de-excitation of the excited states populated via DCE reactions with good energy resolution and detection efficiency, amidst a background composed of transitions from competingreaction channels with far higher cross-sections. To achieve this, the G-NUMEN signalswill be processed in coincidence with those generated by the detection of the reaction ejectiles in the MAGNEX Focal Plane Detector(FPD). Under the expected experimental conditions, G-NUMEN detectors will operate at high counting rates, of the order of hundreds of kHz per detector, while maintaining excellent energy and timing resolutions. The complete array will consist of over 100 LaBr3(Ce) scintillators. Initial tests have been conducted on the first detectors of the array, allowing for the determination of their performance at high rates.

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

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.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

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.

Air pollution poses a significant risk to public health and ecosystems. The use of sophisticated models to simulate the transformation and dispersion of pollutants in the atmosphere is a recognized method to assess air pollution levels and its sources and inform policy decisions for effective mitigation strategies in urban and industrial environments. The reliability of models depends, in part, on the sensitivity to the variance of input parameters, which can introduce uncertainty into the model's predictions. This uncertainty is especially challenging when the input parameters exhibit inherent variability. In this study, we analyse the uncertainty of an integrated emission/dispersion model by evaluating the relationship between input parameters and model outcomes. We uncover new aspects of this relationship while clarifying some previously known dependencies. Wind speed was found to have the most significant effect on calculated concentrations, with small differences leading to substantial concentration variations. The time of day, which reflects prevailing vertical turbulence conditions, was also found to have a notable impact on concentrations, whereas ambient temperature can also significantly influence model’s results. Based on these findings, we offer specific recommendations for regulators and scientists involved in environmental impact assessment to improve the accuracy and reliability of air pollution modelling.

Background: Several kinds of research say that adjuvant blood glucose and blood pressure are usual, but an efficient solution for medical application count remains. This review analyzes the pandemic blood pressure and blood glucose to identify the publications which tell about the clinical practices and research gaps in systematic research.Methods: A study guides to identify the research of Blood Pressure (BP) and Blood Glucose. In order to analyze the recent innovations and research on BP and Blood glucose, the relevant publications and literature from journals were identified.Results: Co-morbidity of BP and Blood glucose is reported as very high. The commonness of blood pressure is thrice as high in type I diabetes patients and almost two times higher in type II diabetes patients when compared to others without Diabetes. The pervasiveness of getting depression is more in the female when compared with men. A detailed study about the linkage of BP and blood glucose tells that the relationship between them is not exactly clear.Limitations: Nearly all reviews providing the linkage of BP and blood glucose are with some limitations and they are not providing any clear conclusion.Conclusions: Present research tells that people having high blood glucose will have a greater chance of getting high blood pressure. More research is needed to state the linkage between BP, blood glucose, and the growth of diabetes mellitus issues and to provide support for managing Diabetes.

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.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

We used an ultrasensitive, broadband optomechanical ultrasound sensor to study the acoustic signals produced by pressurized nitrogen escaping from a variety of small syringes. Harmonically related jet tones extending into the MHz region were observed for a certain range of flow (i.e., Reynolds number), in qualitative agreement with historical studies on gas jets emitted from pipes/orifices of much larger dimensions. For higher turbulent flow rates, we observed broadband ultrasonic emission in the ~ 0 – 5 MHz range, likely limited on the upper end by attenuation in air. These observations are made possible by the broadband, ultrasensitive response (for air-coupled ultrasound) of our optomechanical devices. Aside from their theoretical interest, our results could have practical implications for the non-contact monitoring and detection of early-stage leaks in pressured fluid systems.

(1) Background: The emergence of antibiotic-resistant bacteria is a growing concern in the field of medicine. This has led to the need for alternative treatments for bacterial infections. (2) Methods: The present study aimed to investigate the synergistic effect of a water-based extract of S. fru-tescens and penicillin G on the growth of E. faecalis. (3) Results: The study found that the combina-tion of the plant extract and penicillin G had a synergistic effect on the inhibition of bacterial growth, with a significantly larger inhibition zone observed compared to penicillin G alone. The MIC and MBC tests also demonstrated that the combination of the plant extract and penicillin G was more effective against E. faecalis than penicillin G alone, with a dilution of 1 in 4 yielding 100% inhibition of growth. (4) Conclusion: Although the specific mechanism of action was not dis-cussed in the study, the results suggest that the combination of the plant extract and penicillin G may offer a promising alternative treatment for antibiotic-resistant infections. Further research is needed to determine the active compounds in the plant extract and to investigate the synergistic effect of the combination on other strains of bacteria.

Heterojunctions based on metal halide perovskites (MHPs) are promising systems for photocatalytic hydrogen evolution reaction (HER). In this work, we coupled Cs3Bi2Br9 nanocrystals (NCs), obtained by wet ball milling synthesis, with g-C3N4 nanosheets (NSs) produced by thermal oxidation of bulk g-C3N4 in air. These methods are reproducible, inexpensive, and easy to scale up. Heterojunctions with different loadings of Cs3Bi2Br9 NCs were fully characterized and tested for HER. A relevant improvement of H2 production with respect to pristine carbon nitride was achieved at low NCs levels reaching values up to about 4600 µmol g-1 h-1. This work aims to provide insights on the synthesis of inexpensive and high performing heterojunctions using MHP for photocatalytic applications.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

It has been shown that Human papillomavirus (HPV) infection is associated with several forms of cancer. Additionally, although there are more than 100 types of HPV, more than ten types of it, including types 16 and 18, are considered high-risk. The two proteins that make up the viral capsid of HPV 16 are L1, the major capsid protein, and L2, the minor capsid protein. FDA (The Food and Drug Administration) approved HPV vaccines mostly target L1 and L2 capsid proteins, which facilitate intracellular entry during infection. In this study, it was set out to analyze the creation of phylogenetic relations of L1 nucleic acid sequences of viral isolates. This study also analyzed sequences of three key elements within the amino acid sequences of HPV 16 L1: loops critical for structural stability, nuclear localization signal sequences, and residues implicated in viral attachment. As highlighted by the literature, these elements represent pivotal aspects of viral function. Furthermore, the report highlighted the particular inter-sequence variability within the HPV 16 L1 protein sequences. Overall analysis revealed clustering of sequences primarily due to geographical and characterized by more phylogenetic relatedness within location-specific clusters.

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.

Convolutional neural network architectures have become increasingly complex, which has improved the performance slowly on well-known benchmark datasets in the recent years. In this research, we have analyzed the true need for such complexity. We have introduced G-Net light, a lightweight modified GoogleNet with improved filter count per layer to reduce feature overlaps and complexity. Additionally, by limiting the amount of pooling layers in the proposed architecture, we have exploited the skip connections to minimize the spatial information loss. The investigations on the proposed architecture are evaluated on three retinal vessel segmentation publicly available datasets. The proposed G-Net light outperforms other vessel segmentation architectures by reducing the number of trainable parameters..