Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses.

Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPV+OPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPV+OPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome. Utilizing this HPV+-specific overexpression profile, we previously demonstrated that estrogen attenuates the growth and cell viability of HPV+ keratinocytes and HPV+ cancer cells in vitro. Expansion of this work in vivo failed to replicate this sensitization. The role of stromal support from the tumor microenvironment (TME) has previously been tied to both the HPV lifecycle and in vivo therapeutic responses. Our investigations revealed that in vitro co-culture with fibroblasts attenuated HPV+-specific estrogen growth responses. Continuing to monopolize on the HPV+-specific overexpression of ERα, our co-culture models then assessed the suitability of the selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen, and showed growth attenuation in a variety of our models to one or both of these drugs in vitro. Utilization of these SERMs in vivo closely resembled the sensitization predicted by our co-culture models. Therefore, the in vitro fibroblast co-culture model better predicts in vivo responses. We propose that utilization of our co-culture in vitro model can accelerate cancer therapeutic drug discovery. IMPORTANCE: Human papillomavirus-related cancers (HPV+ cancers) remain a significant public health concern, and specific clinical approaches are desperately needed. In translating drug response data from in vitro to in vivo, the fibroblasts of the adjacent stromal support network play a key role. Our study presents the utilization of a fibroblast 2D co-culture system to better predict translational drug assessments for HPV+ cancers. We also suggest that this co-culture system should be considered for other translational approaches. Predicting even a portion of treatment paradigms that may fail in vivo with a co-culture model will yield significant time, effort, resource, and cost efficiencies.

Autophosphorylation of the KaiC-like protein ArlH inhibits oligomerization and interaction with ArlI, the motor ATPase of the archaellum.

Motile archaea are propelled by the archaellum, whose motor complex consists of the membrane protein ArlJ, the ATPase ArlI, and the ATP-binding protein ArlH. Despite its essential function and the existence of structural and biochemical data on ArlH, the role of ArlH in archaellum assembly and function remains elusive. ArlH is a structural homolog of KaiC, the central component of the cyanobacterial circadian clock. Since autophosphorylation and dephosphorylation of KaiC are central properties for the function of KaiC, we asked whether autophosphorylation is also a property of ArlH proteins. We observed that both ArlH from the euryarchaeon Pyrococcus furiosus (PfArlH) and from the crenarchaeon Sulfolobus acidocaldarius (SaArlH) have autophosphorylation activity. Using a combination of single-molecule fluorescence measurements and biochemical assays, we show that autophosphorylation of ArlH is closely linked to its oligomeric state when bound to hexameric ArlI. These experiments also strongly suggest that ArlH is a hexamer in its ArlI-bound state. Mutagenesis of the putative catalytic residue (Glu-57 in SaArlH) in ArlH results in a reduced autophosphorylation activity and abolished archaellation and motility in S. acidocaldarius, indicating that optimum phosphorylation activity of ArlH is essential for archaellation and motility.

Analysis of performance, bone characteristics, and expression of genes involved in the balance of ionic concentrations in broilers subjected to dietary electrolyte balance levels.

1. Sodium bicarbonate (NaHCO3), potassium carbonate (K2CO3), and ammonium chloride (NH4Cl) are commonly used to correct dietary electrolyte balance (DEB) in birds. However, there are many gaps in the knowledge of their effects when used simultaneously. This study investigated the effect of DEB levels on performance, femur bone characteristics and the expression of genes related to the balance of ionic concentrations in broilers at 21 days of age.2. Male Cobb broiler chickens (n = 245), aged 1-21 d, were divided into groups based on a completely randomised design with five DEB levels (110 mEq/kg, 175 mEq/kg, 240 mEq/kg, 305 mEq/kg, and 370 mEq/kg).3. The performance characteristics measured included body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion (FCR) and body weight birds slaughtered (BWS).4. The bone variables assessed in the femur were weight (WE), relative bone weight (RBWE), length (L), width (WI), maximum load supported (MLS), bone-breaking resistance (BR), and Seedor index (SI). In addition, the expression of CHP1, SLC9A1, and SLC24A3 in the livers, intestines and kidneys of birds was evaluated.5. The DEB level of 370 mEq/kg, at Na+ content of 0.48%, resulted in the highest averages for L, MLS, and BR of the femur. This DEB level increased the expression of SLC9A1 in the liver and SLC24A3 in the intestine. A 240 mEq/kg DEB level decreased the expression of CHP1 in the liver, while supplementation with 110 mEq/kg increased the expression of SLC24A3 in the kidney.6. In conclusion, 370 mEq/kg DEB improved FCR and increased the mean bone characteristics of the femur (L, MLS, and BR) and the expression of SLC9A1 and SLC24A3 in the liver and intestine, respectively. These findings should be considered in future assessments of the effects of DEB levels on broilers.

Entropy analysis of human death uncertainty.

Uncertainty about the time of death is part of one's life, and plays an important role in demographic and actuarial sciences. Entropy is a measure useful for characterizing complex systems. This paper analyses death uncertainty through the concept of entropy. For that purpose, the Shannon and the cumulative residual entropies are adopted. The first may be interpreted as an average information. The second was proposed more recently and is related to reliability measures such as the mean residual lifetime. Data collected from the Human Mortality Database and describing the evolution of 40 countries during several decades are studied using entropy measures. The emerging country and inter-country entropy patterns are used to characterize the dynamics of mortality. The locus of the two entropies gives a deeper insight into the dynamical evolution of the human mortality data series.

Advances in the computational analysis of SARS-COV2 genome.

Given a data-set of Ribonucleic acid (RNA) sequences we can infer the phylogenetics of the samples and tackle the information for scientific purposes. Based on current data and knowledge, the SARS-CoV-2 seemingly mutates much more slowly than the influenza virus that causes seasonal flu. However, very recent evolution poses some doubts about such conjecture and shadows the out-coming light of people vaccination. This paper adopts mathematical and computational tools for handling the challenge of analyzing the data-set of different clades of the severe acute respiratory syndrome virus-2 (SARS-CoV-2). On one hand, based on the mathematical paraphernalia of tools, the concept of distance associated with the Kolmogorov complexity and Shannon information theories, as well as with the Hamming scheme, are considered. On the other, advanced data processing computational techniques, such as, data compression, clustering and visualization, are borrowed for tackling the problem. The results of the synergistic approach reveal the complex time dynamics of the evolutionary process and may help to clarify future directions of the SARS-CoV-2 evolution.

Fractional-order modelling of epoxy resin.

This paper describes epoxy resins by means of electrical impedance spectroscopy (EIS) and the mathematical tool of fractional calculus (FC). Two stages are considered: first, the EIS is used for testing the samples and, second, the measured data are approximated using integer and fractional order models. The FC-based modelling describes the epoxy resins using a small number of parameters that reflect their main characteristics. The EIS data gathered for the epoxies samples are compared with those of different adhesives and sealants by means of a hierarchical clustering algorithm that unravels the relationships between the distinct materials. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.

Rare and extreme events: the case of COVID-19 pandemic.

Complex systems have characteristics that give rise to the emergence of rare and extreme events. This paper addresses an example of such type of crisis, namely the spread of the new Coronavirus disease 2019 (COVID-19). The study deals with the statistical comparison and visualization of country-based real-data for the period December 31, 2019, up to April 12, 2020, and does not intend to address the medical treatment of the disease. Two distinct approaches are considered, the description of the number of infected people across time by means of heuristic models fitting the real-world data, and the comparison of countries based on hierarchical clustering and multidimensional scaling. The computational and mathematical modeling lead to the emergence of patterns, highlighting similarities and differences between the countries, pointing toward the main characteristics of the complex dynamics.

Computational analysis of the SARS-CoV-2 and other viruses based on the Kolmogorov's complexity and Shannon's information theories.

This paper tackles the information of 133 RNA viruses available in public databases under the light of several mathematical and computational tools. First, the formal concepts of distance metrics, Kolmogorov complexity and Shannon information are recalled. Second, the computational tools available presently for tackling and visualizing patterns embedded in datasets, such as the hierarchical clustering and the multidimensional scaling, are discussed. The synergies of the common application of the mathematical and computational resources are then used for exploring the RNA data, cross-evaluating the normalized compression distance, entropy and Jensen-Shannon divergence, versus representations in two and three dimensions. The results of these different perspectives give extra light in what concerns the relations between the distinct RNA viruses.

Understanding COVID-19 nonlinear multi-scale dynamic spreading in Italy.

The outbreak of COVID-19 in Italy took place in Lombardia, a densely populated and highly industrialized northern region, and spread across the northern and central part of Italy according to quite different temporal and spatial patterns. In this work, a multi-scale territorial analysis of the pandemic is carried out using various models and data-driven approaches. Specifically, a logistic regression is employed to capture the evolution of the total positive cases in each region and throughout Italy, and an enhanced version of a SIR-type model is tuned to fit the different territorial epidemic dynamics via a differential evolution algorithm. Hierarchical clustering and multidimensional analysis are further exploited to reveal the similarities/dissimilarities of the remarkably different geographical epidemic developments. The combination of parametric identifications and multi-scale data-driven analyses paves the way toward a closer understanding of the nonlinear, spatially nonuniform epidemic spreading in Italy.

Commensurate and Non-Commensurate Fractional-Order Discrete Models of an Electric Individual-Wheel Drive on an Autonomous Platform.

This paper presents integer and linear time-invariant fractional order (FO) models of a closed-loop electric individual-wheel drive implemented on an autonomous platform. Two discrete-time FO models are tested: non-commensurate and commensurate. A classical model described by the second-order linear difference equation is used as the reference. According to the sum of the squared error criterion (SSE), we compare a two-parameter integer order model with four-parameter non-commensurate and three-parameter commensurate FO descriptions. The computer simulation results are compared with the measured velocity of a real autonomous platform powered by a closed-loop electric individual-wheel drive.

Entropy Analysis of Soccer Dynamics.

This paper adopts the information and fractional calculus tools for studying the dynamics of a national soccer league. A soccer league season is treated as a complex system (CS) with a state observable at discrete time instants, that is, at the time of rounds. The CS state, consisting of the goals scored by the teams, is processed by means of different tools, namely entropy, mutual information and Jensen-Shannon divergence. The CS behavior is visualized in 3-D maps generated by multidimensional scaling. The points on the maps represent rounds and their relative positioning allows for a direct interpretation of the results.

Complexity Analysis of Escher's Art.

Art is the output of a complex system based on the human spirit and driven by several inputs that embed social, cultural, economic and technological aspects of a given epoch. A solid quantitative analysis of art poses considerable difficulties and reaching assertive conclusions is a formidable challenge. In this paper, we adopt complexity indices, dimensionality-reduction and visualization techniques for studying the evolution of Escher's art. Grayscale versions of 457 artworks are analyzed by means of complexity indices and represented using the multidimensional scaling technique. The results are correlated with the distinct periods of Escher's artistic production. The time evolution of the complexity and the emergent patterns demonstrate the effectiveness of the approach for a quantitative characterization of art.

An Entropy Formulation Based on the Generalized Liouville Fractional Derivative.

This paper presents a new formula for the entropy of a distribution, that is conceived having in mind the Liouville fractional derivative. For illustrating the new concept, the proposed definition is applied to the Dow Jones Industrial Average. Moreover, the Jensen-Shannon divergence is also generalized and its variation with the fractional order is tested for the time series.

On the Complexity Analysis and Visualization of Musical Information.

This paper considers several distinct mathematical and computational tools, namely complexity, dimensionality-reduction, clustering, and visualization techniques, for characterizing music. Digital representations of musical works of four artists are analyzed by means of distinct indices and visualized using the multidimensional scaling technique. The results are then correlated with the artists' musical production. The patterns found in the data demonstrate the effectiveness of the approach for assessing the complexity of musical information.

Distinct patterns of exocytosis elicited by Ca2+, Sr2+ and Ba2+ in bovine chromaffin cells.

Three divalent cations can elicit secretory responses in most neuroendocrine cells, including chromaffin cells. The extent to which secretion is elicited by the cations in intact depolarized cells was Ba2+ > Sr2+ ≥ Ca2+, contrasting with that elicited by these cations in permeabilized cells (Ca2+ > Sr2+ > Ba2+). Current-clamp recordings show that extracellular Sr2+ and Ba2+ cause membrane depolarization and action potentials, which are not blocked by Cd2+ but that can be mimicked by tetra-ethyl-ammonium. When applied intracellularly, only Ba2+ provokes action potentials. Voltage-clamp monitoring of Ca2+-activated K+ channels (KCa) shows that Ba2+ reduces outward currents, which were enhanced by Sr2+. Extracellular Ba2+ increases cytosolic Ca2+ concentrations in Fura-2-loaded intact cells, and it induces long-lasting catecholamine release. Conversely, amperometric recordings of permeabilized cells show that Ca2+ promotes the longest lasting secretion, as Ba2+ only provokes secretion while it is present and Sr2+ induces intermediate-lasting secretion. Intracellular Ba2+ dialysis provokes exocytosis at concentrations 100-fold higher than those of Ca2+, whereas Sr2+ exhibits an intermediate sensitivity. These results are compatible with the following sequence of events: Ba2+ blocks KCa channels from both the outside and inside of the cell, causing membrane depolarization that, in turn, opens voltage-sensitive Ca2+ channels and favors the entry of Ca2+ and Ba2+. Although Ca2+ is less permeable through its own channels, it is more efficient in triggering exocytosis. Strontium possesses both an intermediate permeability and an intermediate ability to induce secretion.

A soluble inorganic pyrophosphatase from the cattle tick Rhipicephalus microplus capable of hydrolysing polyphosphates.

Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the cell type. In eukaryotic organisms, polyphosphates have been investigated mainly in mammalian cells, and only a few studies have addressed arthropods. Pyrophosphatases have been shown to regulate polyphosphate metabolism. However, these studies were restricted to trypanosomatids. Here we focus on the tick Rhipicephalus microplus, a haematophagous ectoparasite that is highly harmful to cattle. We produced a recombinant R. microplus pyrophosphatase (rRmPPase) with the aim of investigating its kinetic parameters using polyphosphates as substrate. Molecular docking assays of RmPPase with polyphosphates were also carried out. The kinetic and Hill coefficient parameters indicated that rRmPPase has a greater affinity, higher catalytic efficiency and increased cooperativity for sodium phosphate glass type 15 (polyP15 ) than for sodium tripolyphosphate (polyP3 ). Through molecular docking, we found that polyP3 binds close to the Mg2+ atoms in the catalytic region of the protein, participating in their coordination network, whereas polyP15 interactions involve negatively charged phosphate groups and basic amino acid residues, such as Lys56, Arg58 and Lys193; polyP15 has a more favourable theoretical binding affinity than polyP3 , thus supporting the kinetic data. This study shows, for the first time in arthropods, a pyrophosphatase with polyphosphatase activity, suggesting its participation in polyphosphate metabolism.

Genetic variation in Wnt/ß-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study.

The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/ß-catenin and ER pathways. INTRODUCTION: Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/ß-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). METHODS: The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. RESULTS: Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/ß-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05). CONCLUSIONS: Elite and pre-elite dancers demonstrate high prevalence of low BMD, which is likely related to genetic variants at the Wnt/ß-catenin and ER pathways and not to factors usually associated with BMD in athletes (body weight, menstrual disturbances, energy deficiency).

LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is characterized by increased bone resorption and impaired bone formation. Osteoblast function is regulated by the canonical LRP5/Wnt/ß-catenin pathway. Bone mineral density and RA joint destruction are partially inherited. In line with this, we found significant associations between LRP5 SNPs (p.A1330V, p.N740N, p.V667M) and RA radiographic damage severity. INTRODUCTION: Increased bone resorption and impaired bone formation characterize rheumatoid arthritis (RA). Canonical Wnt/ß-catenin pathway, signalled by lipoprotein receptor-related protein-5 (LRP5), regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied their association with LRP5 single nucleotide polymorphisms (SNPs). METHODS: Clinical data and peripheral blood for biomarkers assessment and LRP5 genotyping were collected from 208 RA patients. Hands and feet X-rays were scored [modified Sharp/van der Heijde Score (SHS), joint space narrowing (JSN), and erosion scores]. Lumbar spine, total left proximal femur, and left hand BMD were assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: TT genotypes for p.A1330V and p.N740N LRP5 SNPs associated with total SHS, erosion score, and hands erosion score; the same for p.A1330V with feet JSN score and p.N740N with hands total score. AG genotype for p.V667M associated with sclerostin and hands JSN score. Femoral BMD associated with TC genotype for p.N740N. Multiple test correction precluded a few of these associations. Among V667M-N740N-A1330V haplotypes: GTT associated with higher feet JSN score (OR = 3.80; p = 0.016) and ATT with higher JSN score (OR = 4.60; p = 0.032), hands total score (OR = 5.65; p = 0.022), and total SHS (OR = 6.74; p = 0.024). CONCLUSION: Significant associations between LRP5 SNPs (p.A1330V, p.N740N, and p.V667M) and the severity of radiographic damage reinforce the evidence of bone destruction heritability in RA.

Satisfaction with life in individuals with a lower limb amputation: The importance of active coping and acceptance.

The aim of this study was to analyze the relationship between sociodemographic/clinical characteristics, coping strategies and satisfaction with life in individuals with lower limb amputation. Sixty-three individuals with a lower limb amputation due to Diabetes and Peripheral Vascular Disease participated in the study and answered measures of coping strategies and satisfaction with life. Findings revealed high dissatisfaction with life. Acceptance and active coping were the most used coping strategies. Satisfaction with life was positively associated with active and planning coping, religion, acceptance and humour. There were differences in coping strategies according to gender, age, marital status, presence of residual limb pain, prosthesis use and mobility level. Results emphasize the differential role of coping strategies, for each individual. Psychosocial interventions need to take into consideration coping strategies during the process of rehabilitation and be specific regarding individuals` sociodemographic and clinical characteristics. This study may help design interventions that answer individuals with lower limb amputations given that coping strategies are a valuable resource in the promotion of satisfaction with life.