We calculate the spectral energy distribution (SED) of electromagnetic radiation and the spectrum of high-energy neutrinos from BL Lac objects in the context of the synchrotron proton blazar model. ...In this model, the high-energy hump of the SED is due to accelerated protons, while most of the low-energy hump is due to synchrotron radiation by co-accelerated electrons. To accelerate protons to sufficiently high energies to produce the high-energy hump, rather high magnetic fields are required. Assuming reasonable emission region volumes and Doppler factors, we then find that in low-frequency peaked BL Lacs (LBLs), which have higher luminosities than high-frequency peaked BL Lacs (HBLs), there is a significant contribution to the high-frequency hump of the SED from pion photoproduction and subsequent cascading, including synchrotron radiation by muons. In contrast, in HBLs we find that the high-frequency hump of the SED is dominated by proton synchrotron radiation. We are able to model the SED of typical LBLs and HBLs, and to model the famous 1997 flare of Markarian 501. We also calculate the expected neutrino output of typical BL Lac objects, and estimate the diffuse neutrino intensity due to all BL Lacs. Because pion photoproduction is inefficient in HBLs, as protons lose energy predominantly by synchrotron radiation, the contribution of LBLs dominates the diffuse neutrino intensity. We suggest that nearby LBLs may well be observable with future high-sensitivity TeV γ-ray telescopes.
Introduction
Depression is a common psychiatric disorder and chronic stress is considered its main environmental risk factor. Recently, immune processes including adenosine triphosphate mediated P2X7 ...receptor (P2X7R) signalling via microglia and macrophages (M/Ms) were found to play a critical role in depression genesis, by linking environmental stress to depression biology and symptoms.
Objectives
To characterize the role of human P2X7R (hP2X7R) in psychosocial and immune stress conditions, both in vitro and in vivo.
Methods
Several, custom designed mouse lines expressing the loxP-flanked, hP2X7R-sequence in the murine P2X7R locus were established. In addition, these mice possess a Cre-sensitive reporter and express a Cre recombinase fused to a mutant estrogen receptor
ligand-binding domain in M/Ms. This enables conditional, tamoxifen-inducible hP2X7R inactivation and simultaneous tdTomato expression. First, we established primary microglia cell cultures and characterized them at baseline and following immune stimulation. Next, we performed behavioural assessment of hP2X7R
wt
and microglia-specific hP2X7R
KO
mice following chronic psychosocial stress. Last, we developed a novel in vivo two-photon microscopy (TPM) approach by use of frontolimbic cranial windows.
Results
Primary hP2X7R
KO
microglia displayed significantly lower IL-1β production, increased survival and decreased morphological activation upon immune stimulation. Although hP2X7R
KO
mice showed a significant increase of locomotor activity at baseline, there was no impact on anxiety- and depressive-like phenotypes. Longitudinal in vivo TPM enabled morphometric characterization of cortical M/Ms over several weeks.
Conclusions
Our results illustrate the great potential of this humanized mouse line for translational psychiatry. In the future, this system could proof useful to evaluate immunomodulatory approaches in chronic stress and depression.
Disclosure
No significant relationships.
A new Monte Carlo program for photohadronic interactions of relativistic nucleons with an ambient photon radiation field is presented. The event generator is designed to fulfill typical astrophysical ...requirements, but can also be used for radiation and background studies at high energy colliders such as LEP2 and HERA, as well as for simulations of photon induced air showers. We consider the full photopion production cross section from the pion production threshold up to high energies. It includes resonance excitation and decay, direct single pion production and diffractive and non-diffractive multiparticle production. The cross section of each individual process is calculated by fitting experimental data, while the kinematics is determined by the underlying particle production process. We demonstrate that our model is capable of reproducing known accelerator data over a wide energy range.
For repairing turbine blades or die and mold forms, additive manufacturing processes are commonly used to build-up new material to damaged sections. Afterwards, a subsequent re-contouring process ...such as 5-axis ball end milling is required to remove the excess material restoring the often complex original geometries. The process design of the re-contouring operation has to be done virtually, because the individuality of the repair cases prevents actual running-in processes. Hard-to-cut materials e.g. titanium or nickel alloys, parts prone to vibration and long tool holders complicate the repair even further. Thus, a fast and flexible material removal simulation is needed. The simulation has to predict suitable processes focusing shape deviations under consideration of process stability for arbitrary complex engagement conditions. In this paper, a dynamic multi-dexel based material removal simulation is presented, which is able to predict high-resolution surface topography and stable parameters for arbitrary processes such as 5-axis ball end milling. In contrast to other works, the simulation is able to simulate an unstable process using discrete cutting edges in real-time.
This study presents the external wind conditions for the design and assessment of wind turbine loading in tropical cyclone regions, including physical constants, wind speed (cyclone classes), wind ...shear, turbulence intensity, turbulence length scale and turbulence spectral models. For the extreme condition, this study focuses on the wind characteristics of the cyclone eye-wall region that carries the strongest wind. For the dynamic response of wind turbine structures, it is worth the effort to characterize the size of eddies constituting turbulent wind. The turbulence integral length scale for cyclone wind is defined and validated with various measurements. Moreover, several turbulence spectral models are validated with field measurements and the ESDU von Karman model gives the best fit. Based on the external wind conditions, a new turbulent cyclone wind model is created with the associated load case(s). A state-of-the-art load analysis is performed using this new cyclone wind model and the results for the relevant turbine components are compared with the existing loads envelope.
Abstract
Phytoplankton blooms fuel marine food webs with labile dissolved carbon and also lead to the formation of particulate organic matter composed of living and dead algal cells. These particles ...contribute to carbon sequestration and are sites of intense algal-bacterial interactions, providing diverse niches for microbes to thrive. We analyzed 16S and 18S ribosomal RNA gene amplicon sequences obtained from 51 time points and metaproteomes from 3 time points during a spring phytoplankton bloom in a shallow location (6-10 m depth) in the North Sea. Particulate fractions larger than 10 µm diameter were collected at near daily intervals between early March and late May in 2018. Network analysis identified two major modules representing bacteria co-occurring with diatoms and with dinoflagellates, respectively. The diatom network module included known sulfate-reducing Desulfobacterota as well as potentially sulfur-oxidizing Ectothiorhodospiraceae. Metaproteome analyses confirmed presence of key enzymes involved in dissimilatory sulfate reduction, a process known to occur in sinking particles at greater depths and in sediments. Our results indicate the presence of sufficiently anoxic niches in the particle fraction of an active phytoplankton bloom to sustain sulfate reduction, and an important role of benthic-pelagic coupling for microbiomes in shallow environments. Our findings may have implications for the understanding of algal-bacterial interactions and carbon export during blooms in shallow-water coastal areas.
During an algal bloom in the North Sea, bacteria living alongside oxygen producing diatoms exploit anoxic niches to reduce sulfate.
The Paleoproterozoic Mako Belt in eastern Senegal is characterised by gold-bearing quartz veins. These are superimposed on the regional Birimian structural complex consisting of volcano-sedimentary ...and intrusive rocks in an Early Proterozoic greenstone belt. In the Mako Belt the multi-stage deformed quartz veins and hydrothermally altered protoliths are characterised by distinctive microstructures and CL properties. The high-grade Au-bearing quartz veins contain one or more generations of hydrothermal quartz. Brecciation of the veins is indicated by cemented fragments of zoned quartz. Gold in the mineralised zones occurs either as inclusions in pyrite or as native gold. Mineralisation typically occurs in vein systems which are brecciated, laminated, and/or show crack-seal textures. Microstructures indicate syn- to late-tectonic mineralisation. Au-mineralised veins contain quartz, carbonate, muscovite, fuchsite, tourmaline, and chlorite. Fluid inclusion studies reveal early, highly saline aqueous inclusions followed by main-stage aqueous-carbonic inclusions of low salinity and finally aqueous low-salinity inclusions. Petrographic observation and microthermometric data suggest that fluid inclusions in main stage quartz were trapped after phase separation from a heterogeneous H2O-CO2 fluid. Gold deposition occurs over a temperature range of 220 to 320°C and pressures of 1.4 to 2.75 kbar (approximately 5 to 10 km depth). The late-stage quartz carbonate vein corresponds to pressures of 0.75 to 1.25 kbar and depths of 3.0 to 4.5 km. A fluid pressure drop due to fracture failure is likely to have triggered Au precipitation. The Mako Belt Au deposits are comparable to a large number of orogenic lode gold deposits in the West African Craton.
Reactive oxygen species (ROS) have been correlated with almost every human disease. Yet clinical exploitation of these hypotheses by pharmacological modulation of ROS has been scarce to nonexistent. ...Are ROS, thus, irrelevant for disease? No. One key misconception in the ROS field has been its consideration as a rather detrimental metabolic by-product of cell metabolism, and thus, any approach eliminating ROS to a certain tolerable level would be beneficial. We now know, instead, that ROS at every concentration, low or high, can serve many essential signaling and metabolic functions. This likely explains why systemic, nonspecific antioxidants have failed in the clinic, often with neutral and sometimes even detrimental outcomes. Recently, drug development has focused, instead, on identifying and selectively modulating ROS enzymatic sources that in a given constellation cause disease while leaving ROS physiologic signaling and metabolic functions intact. As sources, the family of NADPH oxidases stands out as the only enzyme family solely dedicated to ROS formation. Selectively targeting disease-relevant ROS-related proteins is already quite advanced, as evidenced by several phase II/III clinical trials and the first drugs having passed registration. The ROS field is expanding by including target enzymes and maturing to resemble more and more modern, big data-enhanced drug discovery and development, including network pharmacology. By defining a disease based on a distinct mechanism, in this case ROS dysregulation, and not by a symptom or phenotype anymore, ROS pharmacology is leaping forward from a clinical underperformer to a proof of concept within the new era of mechanism-based precision medicine. SIGNIFICANCE STATEMENT: Despite being correlated to almost every human disease, nearly no ROS modulator has been translated to the clinics yet. Here, we move far beyond the old-fashioned misconception of ROS as detrimental metabolic by-products and suggest 1) novel pharmacological targeting focused on selective modulation of ROS enzymatic sources, 2) mechanism-based redefinition of diseases, and 3) network pharmacology within the ROS field, altogether toward the new era of ROS pharmacology in precision medicine.
The spectral energy distribution (SED) of gamma-ray (γ-ray) loud BL Lac objects typically has a double-humped appearance usually interpreted in terms of synchrotron self-Compton models. In proton ...blazar models, the SED is instead explained in terms of acceleration of protons and subsequent cascading. We discuss a variation of the synchrotron proton blazar model, first proposed by Mücke and Protheroe (Proc. Workshop GeV–TeV Astrophysics: Toward a Major Atmospheric Cherenkov Telescope VI, Snowbird, Utah, submitted for publication), in which the low energy part of the SED is mainly proton synchrotron radiation by electrons co-accelerated with protons, which produce the high energy part of the SED mainly as synchrotron radiation.
As an approximation, we assume non-relativistic shock acceleration which could apply if the bulk of the plasma in the jet frame were non-relativistic. Our results may therefore change if a relativistic equation of state was used. We consider the case where the maximum energy of the accelerated protons is above the threshold for pion photoproduction interactions on the synchrotron photons of the low energy part of the SED. Using a Monte Carlo/numerical technique to simulate the interactions and subsequent cascading of the accelerated protons, we are able to fit the high-energy γ-ray portion of the observed SED of Markarian 501 during the April 1997 flare. We find that the emerging cascade spectra initiated by γ-rays from π
0 decay and by e
± from μ
± decay turn out to be relatively featureless. Synchrotron radiation produced by μ
± from π
± decay, and even more importantly by protons, and subsequent synchrotron-pair cascading, is able to reproduce well the high energy part of the SED. For this fit, we find that synchrotron radiation by protons dominates the TeV emission, pion photoproduction being less important with the consequence that we predict a lower neutrino flux than in other proton blazar models.
PDF
