The ESO UVES/FEROS Large Programs of TESS OB pulsators. I. Global stellar parameters from high-resolution spectroscopy

Modern stellar structure and evolution theory experiences a lack of observational calibrations for the interior physics of intermediate- and high-mass stars. This leads to discrepancies between theoretical predictions and observed phenomena mostly related to angular momentum and element transport. Analyses of large samples of massive stars connecting state-of-the-art spectroscopy to asteroseismology may provide clues on how to improve our understanding of their interior structure. We aim to deliver a sample of O- and B-type stars at metallicity regimes of the Milky Way and the Large Magellanic Cloud (LMC) galaxies with accurate atmospheric parameters from high-resolution spectroscopy, along with a detailed investigation of line-profile broadening, for future asteroseismic studies. After describing the general aims of our two Large Programs, we develop dedicated methodology to fit spectral lines and deduce accurate global stellar parameters from high-resolution multi-epoch UVES and FEROS spectroscopy. We use the best available atmosphere models for three regimes covered by our global sample, given its breadth in terms of mass, effective temperature, and evolutionary stage. Aside from accurate atmospheric parameters and locations in the Hertzsprung-Russell diagram, we deliver detailed analyses of macroturbulent line broadening, including estimation of the radial and tangential components. We find that these two components are difficult to disentangle from spectra with signal-to-noise ratios below 250. Future asteroseismic modelling of the deep interior physics of the most promising stars in our sample will improve the existing dearth of such knowledge for large samples of OB stars, including those of low metallicity in the LMC.Comment: Accepted for publication in Astronomy & Astrophysic

Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients

Sarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, and non-Lofgren’s syndrome (nLS) is a chronic type of disease with a high risk of pulmonary fibrosis. Our study was aimed to investigate the balance of main “polarized” CD4+ central and effector memory T cells from treatment-naive patients with pulmonary sarcoidosis (LS (n = 19) and nLS (n = 63)) compared to healthy volunteers (HC, n = 48). This marker might be used as immunological markers for predicting severity of this disorder. Multicolor flow cytometry analysis demonstrated that the patients with nLS showed significantly low levels of relative and absolute numbers of CD3+CD4+ lymphocytes if compared to patients with LS and control group (38.94% (31.33-44.24) versus 48.96% (43.34-53.54) and 47.63% (43.82-52.73), p < 0.001 in both cases). Moreover, patients with nLS had reduced frequencies and absolute numbers of “naive”, CM and EM Th cells if compared with healthy controls. Furthermore, the patients with LS showed increased relative and absolute numbers of peripheral blood EM Th cells, capable for migration to peripheral inflamed tissues, when compared with nLS. Finally, patients with LS had increased frequencies and absolute numbers of effector TEMRA Th cells as compared to HC and nLS. Next, significant differences Th1 and Th2 cells frequencies were shown between the patients with nLS and HC (9.64% (7.06-13.65) versus 13.80% (11.24-18.03) with p < 0.001, and 11.96% (9.86-14.78) versus 10.67% (9.13-12.98) with p = 0.048, respectively). But there were no significant differences in the relative numbers of CXCR5-CCR6+Th17 and CXCR5+ follicular T helper cells (Tfh) between the groups. Finally, both groups of patients with pulmonary sarcoidosis contained low proportions of “non-classical” Th17 and DN Th17 cell, but increased levels of DP Th17 cells within total CXCR5-CCR6+ CM Th if compared with HC. Nevertheless, patients with nLS had increased frequency of “classical” Th17 in comparison with healthy controls. A very similar imbalance between different Th17 cell subsets was observed within total CXCR5CCR6+ effector memory Th, that were able to migrate from the bloodstream to the sites of infection, or tissue injury. Taken together, the data suggest that the proportions of Th17 cell subsets in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and these cells could serve as a new therapeutic target

ROLE OF THE CELLULAR IMMUNITY IN THE PATHOGENESIS OF BRAIN CONTUSION

Traumatic brain injury (TBI) is one of the most common pathologies of the central nervous system in the world, and the use of structural neuroimaging methods – computed tomography (CT) and magnetic resonance imaging (MRI) – often doesn’t allow assessment of the severity of the brain injury that has occurred. This situation predetermines the need to search for new methods of differential diagnosis of the severity of TBI and predicting the risk of consequences.One of these promising areas is the study of the immune status, since traumatic brain injury is characterized by a high rate of complications.One of these promising areas is the study of the immune status in patients with TBI in the acute period. It is now known that in response to brain damage, a response from the immune system is triggered.The reactions from the immune system, which develop after brain injury and directed against its own antigens, in the early period of the disease are related to damage to the nervous tissue. However, according to the latest available data, they are subsequently able to stimulate the processes of repair and regeneration in the brain tissue. In the course of damage to the nervous tissue, in response to endogenous molecules formed during the destruction of cells and the extracellular matrix, the cells of the immune system are activated.Current evidence indicates that T-cells play a role in both the formation of secondary damage and repair mechanisms. They are able to protect neurons through the production of neurotrophic factors such as brain neurotrophic factor (BDNF), which stimulates the growth of neurons, the formation of synapses.Using multicolor cytometric analysis within the framework of this work, a study was carried out to determine the number of the main subpopulations of CD3+CD4+-lymphocytes. The relative number of Th17 (CXCR5- CXCR3- CCR6+CCR4- ) and Th17/Th22 (CXCR5- CXCR3- CCR6+CCR4+), Th1/Th17 (CXCR5- CXCR3+CCR6+CCR4- ) among total CD45RA-negative CD3+CD4+-cells population is significantly increased in comparison with the values in the control group, in turn, the Th1(CXCR5- CXCR3+CCR6- CCR4- ) subpopulations among total CD45RA-negative CD3+CD4+-cells are significantly decreased with the values in the control group. The results obtained so far make it possible to consider immune responses among the key links in the pathogenesis of brain contusion TBI. And, perhaps, a comprehensive immunological examination of the victims in the first day after the injury will determine the parameters that will help predict the nature of possible complications in patients with brain contusion

CHEMOKINE RECEPTORS AT DISTINCT DIFFERENTIATION STAGES OF T-HELPERS FROM PERIPHERAL BLOOD

Expression of chemokine receptors (CCR4, CCR6, CXCR3 and CXCR5) on T-helper (Th) cells at various levels of differentiation in a group of healthy volunteers (n = 52) was assessed on the basis of CD45RA and CD62L expression, using the eight-color flow cytometry. It was found that the “naive” T helper cells (N) with CD45RA+CD62L+ phenotype express CXCR3 (4.94±0.39%), and CXCR5 (3.63±0.25%). About 50% of central memory T helpers (CD45RA–CD62L+, CM) were CXCR3 positive, and 43.72±1.27% of CM cells expressed CCR6, whereas CXCR5 and CCR4 levels were about 30%. Furthermore, CXCR3 was expressed by 76.76±0.75% of the CD3+CD4+CD45RA–CD62L– (EM) population, and similar values were obtained for CCR6, while the relative abundance of CXCR5+ cells decreased to 13.68±0.50%, and CCR4 levels did not change and accounted for 33.26±1.13% positive cells. Likewise, co-expression of the chemokine receptors was studied for the abovementioned subpopulations of T helper cells. Among the CXCR5– Th, Th1 cells were identified as CXCR3+CCR6–CCR4– (this subset also contained Th9), and CXCR3+CCR6+CCR4– subsets, referred to as Th1/Th17. Th2 were detected on the basis of CCR4 expression in absence of all other chemokine receptors. In addition to the mentioned Th1/Th17 populations, Th 17 cells were found in the subsets of Th17 CXCR3–CCR6+CCR4– and CXCR3–CR6+CCR4+. The latter also contained a Th22 population. Follicular Th cell populations (CXCR5+) consisted of, at least, six different subsets: CXCR3–CCR6–CCR4– (Tfh/Tfh2), CXCR3–CCR6–CCR4+ (Tfh2), CXCR3-CCR6+CCR4–(Tfh17), CXCR3–CCR6+CCR4+ (Tfh17), CXCR3+CCR6–CCR4– (Tfh1) and CXCR3+CCR6+CCR4–(Tfh1/Tfh17). The cells with Th1/Th9 and Th1/Th17 phenotypes dominated among CM (about 13%), whereas their relative abundance within EM increased to 22.37±1.69% and 31.69±1.52%, respectively. The amounts of Th2 were 8.15±0.46% within CM, and only 1.72±0.15% for EM population. For the cells with Th17/Th22 phenotype, these values are 8.07±0.30% and 12.03±0.57%, respectively. The main Tfh subsets were represented among the CM T-helpers: the relative content of Tfh/Tfh2 was 5.79 0.26%, Tfh2, 1.34±0.07%; Tfh17 with CXCR3-CCR6+CCR4– and CXCR3-CCR6+CCR4+ phenotypes made up to 6.22±0.28% and 3.28±0.16%, as well as Tfh1 (7.68±0.31%), and Tfh1/Tfh17 (4.02±0.17%), respectively. Relative content of the mentioned Tfh subsets was decreased > 2-fold within effector memory Th subpopulation. The data obtained may be applied for diagnostics of different immunopathological conditions and could be used as a comparison group in further studies

Peripheral blood B cell subsets from patients with various activity of chronic sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology, characterized by development of necrosis-free epithelioid cell granulomas, resulting in hyperactivation of various cells of the immune system. The role of humoral mechanisms in the pathogenesis of sarcoidosis is less studied than cell-mediated. It is necessary to study the role of activation or the anergy of the B cell development of immunity in sarcoidosis, the degree of its activity and the characteristics of the clinical course of the disease. Our study was aimed at investigating the characteristics of the B cells subsets in the peripheral blood of patients with chronic sarcoidosis (n = 41), depending on the activity of the disease. The control was peripheral blood samples from healthy volunteers (n = 43). Objective clinical and instrumental criteria, angiotensin converting enzyme (ACE) were used to determine the activity of the disease. Using flow cytometry analysis of peripheral blood cell B cells were determined based on two approaches: expression of IgD/CD38 (“Bm1-Bm5” classification) and IgD/CD27. In patients with sarcoidosis there was a significantly higher relative number of Bm2 "activated" naive cells" (IgD+CD38+) than in conditionally healthy volunteers, 65.38% versus 55,66% (p < 0.001). The relative and absolute contents of eBm5 (IgD-CD38+) and Bm5 (IgD-CD38+) memory cells were significantly lower in the group of patients with sarcoidosis relative to the control group. Relative values: 6.59% versus 13.31%, (p < 0.001), and 3.43% versus 8.49%, (p < 0.001), respectively. It was shown that with an increased level of ACE in the peripheral blood of patients, the number of naive Bm1 cells (IgD+CD38-) was significantly reduced, r = -0.557, p < 0.001. The relative content of memory B cells that did not switch the class of synthesized antibodies (IgD+CD27+) in the group of patients was reduced to 6,25%, and in the control group — 12,95% (p<0.001). The number of memory cells that switched the class of synthesized antibodies (IgD-CD27+) was also significantly reduced in patients with sarcoidosis and amounted to 6.75% versus 16.50% in the control group (p < 0.001). In patients with high levels of ACE, there was an increase in the relative content of naive B cells (IgD+CD27-), r = 0.532, p < 0.001. An inverse relationship was established between the number of memory B cells (IgD+CD27+) and ACE levels, r = -0.565, p < 0.001. These results indicate the important role of the B cell immune response in the pathogenesis of sarcoidosis and make it possible to evaluate the characteristics of the humoral response with various degrees of disease activity

Features of T lymphocyte subpopulation profile in patients with ankylosing spondylitis undergoing genetically engineered biological therapy

The aim of current study was to compare profiles of T cell subsets in the patients with ankylosing spondylitis (AS) who received different modes of genetically engineered biological therapy (GEBT). The research involved 58 patients aged 20 to 58 years diagnosed with AS and treated with anti-TNFα and antiIL-17 drugs, as well as those receiving common anti-inflammatory therapy. The AS diagnostics was based on the modified New York criteria. Disease activity was assessed by means of nomenclature approved by the Assessment of Spondyloarthritis International Society and Outcome Measures in Rheumatology. 45 healthy people aged 18 to 57 were included into the control group. Peripheral blood T cell subsets were analysed by multicolor flow cytometry. It was found that the T lymphocyte subpopulation profiles in AS patients showed significant differences depending on the therapy type. First, T lymphocyte counts were decreased in AS patients receiving traditional anti-inflammatory therapy, whereas relative numbers of T cells with high levels of effector potential and cytokine secretion were increased. Negative correlations between the levels of effector memory and pre-effector cytotoxic T cells and other laboratory and clinical indexes of inflammatory activity in AS may reflect lower efficiency of traditional therapy. Next, the levels of main T cell subsets in AS patients during antiIL-17 therapy fully corresponded to the control values. However, based on numerous correlations between immunological and clinical laboratory parameters, it was concluded that anti-IL-17 therapy had an inhibitory effect on the joint inflammation activity, while the state of T cell subsets was mainly dependent on standard anti-inflammatory therapy. The most pronounced changes in T cell subsets were found in AS patients during anti-TNFα therapy was associated with decreased effector potential of Th cells and cytotoxic T lymphocytes. At the same time, the lowest frequency of extraskeletal manifestations was found in AS patients treated with anti-TNFα drugs. Finally, the higher efficiency of GEBT, compared with conventional methods of therapy, is determined by the effects upon immune targets of AS pathogenesis which manifested, e.g., by changes in the T lymphocyte subpopulation profile. Moreover, usage of anti-TNFα versus anti-IL-17 inhibitors was associated with greater effect upon phenotypic profile of T cells

Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile

Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme

Elastic properties of mono- and polycrystalline hexagonal AlB2-like diborides of s, p and d metals from first-principles calculations

We have performed accurate ab initio total energy calculations using the full-potential linearized augmented plane wave (FP-LAPW) method with the generalized gradient approximation (GGA) for the exchange-correlation potential to systematically investigate elastic properties of 18 stable, meta-stable and hypothetical hexagonal (AlB2-like) metal diborides MB2, where M = Na, Be, Mg, Ca, Al, Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Ag and Au. For monocrystalline MB2 the optimized lattice parameters, independent elastic constants (Cij), bulk modules (B), shear modules (G) are obtained and analyzed in comparison with the available theoretical and experimental data. For the first time numerical estimates of a set of elastic parameters of the polycrystalline MB2 ceramics (in the framework of the Voigt-Reuss-Hill approximation), namely bulk and shear modules, compressibility, Young's modules, Poisson's ratio, Lame's coefficients are performed.Comment: 24 pages, 3 figure

Representation of financial markets in macro-economic transition models-a review and suggestions for extensions

As the energy transition accelerates and renewable energy technologies become cost-competitive with fossil fuels in many countries, the availability of finance could become a bottleneck. Integrated assessment models (IAMs) and other macro-economic transition (MET) models typically do not feature detailed financial markets and do not sufficiently consider financing barriers and opportunities for the transition to carbon neutrality. While progress has been made in the representation of financial markets in macro-models since the financial crisis of 2008 the focus has been on financial (in)stability of the financial sector, not its ability to finance investment projects in the energy transition. Hence, a crucial gap remains, preventing macro model-based analysis of financing barriers and policy interventions that may accelerate the energy transition. In this article we review how state-of-the-art macro-economic models consider the financial sector. From this review we identify what elements are still missing to adequately model the financial dynamics and challenges for the energy transition specifically. Based on a discussion of relevant parts of the finance literature, we then propose four steps to improve the representation of finance in global IAMs and MET models more generally.ISSN:1748-9326ISSN:1748-931