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Reconstructing the biogeographic history of groups present in continuous arid landscapes is challenging due to the difficulties in defining discrete areas for analyses, and even more so when species largely overlap both in terms of geography and habitat preference. In this study, we use a novel approach to estimate ancestral areas for the small plant genus Centipeda. We apply continuous diffusion of geography by a relaxed random walk where each species is sampled from its extant distribution on an empirical distribution of time-calibrated species-trees. Using a distribution of previously published substitution rates of the internal transcribed spacer (ITS) for Asteraceae, we show how the evolution of Centipeda correlates with the temporal increase of aridity in the arid zone since the Pliocene. Geographic estimates of ancestral species show a consistent pattern of speciation of early lineages in the Lake Eyre region, with a division in more northerly and southerly groups since ∼840 ka. Summarizing the geographic slices of species-trees at the time of the latest speciation event (∼20 ka), indicates no presence of the genus in Australia west of the combined desert belt of the Nullabor Plain, the Great Victoria Desert, the Gibson Desert, and the Great Sandy Desert, or beyond the main continental shelf of Australia. The result indicates all western occurrences of the genus to be a result of recent dispersal rather than ancient vicariance. This study contributes to our understanding of the spatiotemporal processes shaping the flora of the arid zone, and offers a significant improvement in inference of ancestral areas for any organismal group distributed where it remains difficult to describe geography in terms of discrete areas.

Rotordynamic simulations with nonlinear hydrodynamic bearing forces require a solution of the Reynolds equation at every time step. As a computationally efficient alternative to the standard numerical methods, a semi‐analytical solution based on the scaled boundary finite element method (SBFEM) was developed recently. Through a discretization of the hydrodynamic pressure (dependent variable) along the circumferential but not the axial coordinate, the partial differential equation is transformed into a system of ordinary differential equations. This system of differential equations is referred to as SBFEM equation and can be solved exactly if the influence of shaft tilting is neglected. In common numerical models, this influence can be taken into account without difficulties, but as far as this semi‐analytical approach is concerned, shaft tilting complicates the equations substantially. Therefore, previous studies on the SBFEM solution of the Reynolds equation were conducted without consideration of this effect. The formulation presented in the work at hand no longer requires this simplification. The terms representing the influence of shaft tilting in the SBFEM equation are handled by the perturbation method. The pressure field is expressed by a series expansion, where the solution of order k$k$ correlates to the kth$k\mathrm{th}$ power of a perturbation parameter chosen proportional to the tilting angle. The differential equation governing the kth$k\mathrm{th}$ solution contains lower‐order solutions on its right‐hand side, implying a recursive computation of the series from lowest to highest order. A universal expression for the general solution is formulated, where only the coefficients and the maximum power of the axial coordinate differ for every k$k$. This allows the implementation of a general algorithm with no inherent limitation regarding the maximum order of perturbation. For verification, the pressure fields computed by the proposed method are compared to a numerical reference solution, showing that the series converges to the correct result for the investigated set of parameters. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig, and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). In addition, we demonstrate that chronic application of FR prevented and also reversed Sugen (Su)Hx-induced PH in mice. We also demonstrate that Gq inhibition reduces proliferation and migration of PASMCs in vitro. Thus, our work illustrates a dominant role of Gq proteins for pulmonary vasoconstriction as well as remodeling and proposes direct Gq inhibition as a powerful pharmacological strategy in PH. Synopsis: This study highlights the decisive role of Gq proteins in pulmonary vasoconstriction and vascular remodeling, the main hallmarks of pulmonary hypertension (PH), and introduces the pharmacological pan-Gq inhibitor FR900359 (FR) as a potential therapeutic compound. Gq inhibition by FR induced strong pulmonary vasorelaxation in mice, pigs, and humans ex vivo. Gq inhibition by FR reduced cell growth and migration of pulmonary artery smooth muscle cells in vitro. FR prevented and reversed hypoxia-induced PH in mice in vivo. This study highlights the decisive role of Gq proteins in pulmonary vasoconstriction and vascular remodeling, the main hallmarks of pulmonary hypertension (PH), and introduces the pharmacological pan-Gq inhibitor FR900359 (FR) as a potential therapeutic compound. [ABSTRACT FROM AUTHOR]

Context. Gas in protoplanetary disks mostly cools via thermal accommodation with dust particles. Thermal relaxation is thus highly sensitive to the local dust size distributions and the spatial distribution of the grains. So far, the interplay between thermal relaxation and gas turbulence has not been dynamically modeled in hydrodynamic simulations of protoplanetary disks with dust. Aims. We aim to study the effects of the vertical shear instability (VSI) on the thermal relaxation times, and vice versa. We are particularly interested in the influence of the initial dust grain size on the VSI and whether the emerging turbulence is sustained over long timescales. Methods. We ran three axisymmetric hydrodynamic simulations of a protoplanetary disk including four dust fluids that initially resemble MRN size distributions of different initial grain sizes. From the local dust densities, we calculated the thermal accommodation timescale of dust and gas and used the result as the thermal relaxation time of the gas in our simulation. We included the effect of dust growth by applying the monodisperse dust growth rate and the typical growth limits. Results. We find that the emergence of the VSI is strongly dependent on the initial dust grain size. Coagulation also counteracts the emergence of hydrodynamic turbulence in our simulations, as shown by others before. Starting a simulation with larger grains (100 μm) generally leads to a less turbulent outcome. While the inner disk regions (within ∼70 au) develop turbulence in all three simulations, we find that the simulations with larger particles do not develop VSI in the outer disk. Conclusions. Our simulations with dynamically calculated thermal accommodation times based on the drifting and settling dust distribution show that the VSI, once developed in a disk, can be sustained over long timescales, even if grain growth is occurring. The VSI corrugates the dust layer and even diffuses the smaller grains into the upper atmosphere, where they can cool the gas. Whether the instability can emerge for a specific stratification depends on the initial dust grain sizes and the initial dust scale height. If the grains are initially ≳100 μm and if the level of turbulence is initially assumed to be low, we find no VSI turbulence in the outer disk regions. [ABSTRACT FROM AUTHOR]

Objective The possibility of combining real and virtual environments is driving the increased use of augmented reality (AR) in education, including medical training. The aim of this multicentre study was to evaluate the students' perspective on the AR-based Rheumality GO!® app as a new teaching concept, presenting six real anonymized patient cases with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). Methods The study encompassed 347 undergraduate medical students (232 women and 115 men) from four medical universities in Germany (Jena, Bad Nauheim/Gießen, Nuremberg, Erlangen). The course was divided into a theoretical refresher lecture followed by six AR-based cases in each of the three indications presented in the Rheumality GO! app. All participants evaluated the course after completion, assessing the benefit of the app from a student's perspective using a questionnaire with 16 questions covering six subject areas. Results The use of the AR-based app Rheumality GO! improved the understanding of pathologies in RA, PsA and axSpA for 99% of the participants. For 98% of respondents, the concept of AR with real patient data has made a positive impact on the teaching environment. On the other hand, 82% were in favour of the use of virtual tools (e.g. AR) in addition to this conventional approach. Conclusion The results of our survey showed that from the medical students' perspective, an AR-based concept like the Rheumality GO! app can complement rheumatology teaching in medical school as an effective and attractive tool though not replace bedside teaching. [ABSTRACT FROM AUTHOR]

Background/Aims The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes. Methods A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice. Results For babies receiving ROP treatment, we recommend patient demographics, systemic comorbidities, ROP status, treatment details, ophthalmic and systemic complications of treatment, ophthalmic and neurodevelopmental outcomes at initial treatment, any episodes of retreatment and follow-up examinations in the short and long-term to be collected for use in ROP studies, registries and routine clinical practice. Conclusions We recommend these parameters to be used in registries and future studies of ROP treatment, to reduce the variation seen in previous reports and allow meaningful assessments and comparisons. They form the basis of the EU-ROP and the Fight Childhood Blindness! ROP Registries. [ABSTRACT FROM AUTHOR]

Background: Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression. Methods: We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity. Results: PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors. Conclusions: We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface to bottom ocean biogeochemical data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of water samples. This update of GLODAPv2, v2.2019, adds data from 116 cruises to the previous version, extending its coverage in time from 2013 to 2017, while also adding some data from prior years. GLODAPv2.2019 includes measurements from more than 1.1 million water samples from the global oceans collected on 840 cruises. The data for the 12 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, CFC-11, CFC-12, CFC-113, and CCl4) have undergone extensive quality control, especially systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but updated to WOCE exchange format and (ii) as a merged data product with adjustments applied to minimize bias. These adjustments were derived by comparing the data from the 116 new cruises with the data from the 724 quality-controlled cruises of the GLODAPv2 data product. They correct for errors related to measurement, calibration, and data handling practices, taking into account any known or likely time trends or variations. The compiled and adjusted data product is believed to be consistent to better than 0.005 in salinity, 1 % in oxygen, 2 % in nitrate, 2 % in silicate, 2 % in phosphate, 4 µmol kg−1 in dissolved inorganic carbon, 4 µmol kg−1 in total alkalinity, 0.01–0.02 in pH, and 5 % in the halogenated transient tracers. The compilation also includes data for several other variables, such as isotopic tracers. These were not subjected to bias comparison or adjustments. The original data, their documentation and DOI codes are available in the Ocean Carbon Data System of NOAA NCEI (https://www.nodc.noaa.gov/ocads/oceans/GLODAPv2_2019/, last access: 17 September 2019). This site also provides access to the merged data product, which is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/xnme-wr20 (Olsen et al., 2019). The product files also include significant ancillary and approximated data. These were obtained by interpolation of, or calculation from, measured data. This paper documents the GLODAPv2.2019 methods and provides a broad overview of the secondary quality control procedures and results.