A future very-high-energy view of our Galaxy

The survey of the inner Galaxy with H.E.S.S. was remarkably successful in detecting a wide range of new very-high-energy gamma-ray sources. New TeV gamma-ray emitting source classes were established, although several of the sources remain unidentified, and progress has been made in understanding particle acceleration in astrophysical sources. In this work, we constructed a model of a population of such very-high-energy gamma-ray emitters and normalised the flux and size distribution of this population model to the H.E.S.S.-discovered sources. Extrapolating that population of objects to lower flux levels we investigate what a future array of imaging atmospheric telescopes (IACTs) such as AGIS or CTA might detect in a survey of the Inner Galaxy with an order of magnitude improvement in sensitivity. The sheer number of sources detected together with the improved resolving power will likely result in a huge improvement in our understanding of the populations of galactic gamma-ray sources. A deep survey of the inner Milky Way would also support studies of the interstellar diffuse gamma-ray emission in regions of high cosmic-ray density. In the final section of this paper we investigate the science potential for the Galactic Centre region for studying energy-dependent diffusion with such a future array.Comment: Proceeding of "Heidelberg International Symposium on High Energy Gamma-Ray Astronomy", held in Heidelberg, 7-11 July 2008, submitted to AIP Conference Proceedings. 4 pages, 4 figure

The significance of bioelectricity on all levels of organization of an organism. Part 1: From the subcellular level to cells

Bioelectricity plays an essential role in the structural and functional organization of biological organisms. In this first part of our multi-part series of articles, we summarise the importance of bioelectricity for the basic structural level of biological organization, i.e. from the subcellular level (charges, ion channels, molecules and cell organelles) to cells

Dysregulated Immunity in Pulmonary Hypertension: From Companion to Composer

Pulmonary hypertension (PH) represents a grave condition associated with high morbidity and mortality, emphasizing a desperate need for innovative and targeted therapeutic strategies. Cumulative evidence suggests that inflammation and dysregulated immunity interdependently affect maladaptive organ perfusion and congestion as hemodynamic hallmarks of the pathophysiology of PH. The role of altered cellular and humoral immunity in PH gains increasing attention, especially in pulmonary arterial hypertension (PAH), revealing novel mechanistic insights into the underlying immunopathology. Whether these immunophysiological aspects display a universal character and also hold true for other types of PH (e.g., PH associated with left heart disease, PH-LHD), or whether there are unique immunological signatures depending on the underlying cause of disease are points of consideration and discussion. Inflammatory mediators and cellular immune circuits connect the local inflammatory landscape in the lung and heart through inter-organ communication, involving, e.g., the complement system, sphingosine-1-phosphate (S1P), cytokines and subsets of, e.g., monocytes, macrophages, natural killer (NK) cells, dendritic cells (DCs), and T- and B-lymphocytes with distinct and organ-specific pro- and anti-inflammatory functions in homeostasis and disease. Perivascular macrophage expansion and monocyte recruitment have been proposed as key pathogenic drivers of vascular remodeling, the principal pathological mechanism in PAH, pinpointing toward future directions of anti-inflammatory therapeutic strategies. Moreover, different B- and T-effector cells as well as DCs may play an important role in the pathophysiology of PH as an imbalance of T-helper-17-cells (T(H)17) activated by monocyte-derived DCs, a potentially protective role of regulatory T-cells (T-reg) and autoantibody-producing plasma cells occur in diverse PH animal models and human PH. This article highlights novel aspects of the innate and adaptive immunity and their interaction as disease mediators of PH and its specific subtypes, noticeable inflammatory mediators and summarizes therapeutic targets and strategies arising thereby

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Analysis of the capacity of google trends to measure interest in conservation topics and the role of online news

With the continuous growth of internet usage, Google Trends has emerged as a source of information to investigate how social trends evolve over time. Knowing how the level of interest in conservation topics--approximated using Google search volume--varies over time can help support targeted conservation science communication. However, the evolution of search volume over time and the mechanisms that drive peaks in searches are poorly understood. We conducted time series analyses on Google search data from 2004 to 2013 to investigate: (i) whether interests in selected conservation topics have declined and (ii) the effect of news reporting and academic publishing on search volume. Although trends were sensitive to the term used as benchmark, we did not find that public interest towards conservation topics such as climate change, ecosystem services, deforestation, orangutan, invasive species and habitat loss was declining. We found, however, a robust downward trend for endangered species and an upward trend for ecosystem services. The quantity of news articles was related to patterns in Google search volume, whereas the number of research articles was not a good predictor but lagged behind Google search volume, indicating the role of news in the transfer of conservation science to the public

High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks.

During 2015 to 2016, Brazil reported more Zika virus (ZIKV) cases than any other country, yet population exposure remains unknown. Serological studies of ZIKV are hampered by cross-reactive immune responses against heterologous viruses. We conducted serosurveys for ZIKV, dengue virus (DENV), and Chikungunya virus (CHIKV) in 633 individuals prospectively sampled during 2015 to 2016, including microcephaly and non-microcephaly pregnancies, HIV-infected patients, tuberculosis patients, and university staff in Salvador in northeastern Brazil using enzyme-linked immunosorbent assays (ELISAs) and plaque reduction neutralization tests. Sera sampled retrospectively during 2013 to 2015 from 277 HIV-infected patients were used to assess the spread of ZIKV over time. Individuals were georeferenced, and sociodemographic indicators were compared between ZIKV-positive and -negative areas and areas with and without microcephaly cases. Epidemiological key parameters were modeled in a Bayesian framework. ZIKV seroprevalence increased rapidly during 2015 to 2016, reaching 63.3% by 2016 (95% confidence interval [CI], 59.4 to 66.8%), comparable to the seroprevalence of DENV (75.7%; CI, 69.4 to 81.1%) and higher than that of CHIKV (7.4%; CI, 5.6 to 9.8%). Of 19 microcephaly pregnancies, 94.7% showed ZIKV IgG antibodies, compared to 69.3% of 257 non-microcephaly pregnancies (P = 0.017). Analyses of sociodemographic data revealed a higher ZIKV burden in low socioeconomic status (SES) areas. High seroprevalence, combined with case data dynamics allowed estimates of the basic reproduction number R0 of 2.1 (CI, 1.8 to 2.5) at the onset of the outbreak and an effective reproductive number Reff of <1 in subsequent years. Our data corroborate ZIKV-associated congenital disease and an association of low SES and ZIKV infection and suggest that population immunity caused cessation of the outbreak. Similar studies from other areas will be required to determine the fate of the American ZIKV outbreak.IMPORTANCE The ongoing American Zika virus (ZIKV) outbreak involves millions of cases and has a major impact on maternal and child health. Knowledge of infection rates is crucial to project future epidemic patterns and determine the absolute risk of microcephaly upon maternal ZIKV infection during pregnancy. For unknown reasons, the vast majority of ZIKV-associated microcephaly cases are concentrated in northeastern Brazil. We analyzed different subpopulations from Salvador, a Brazilian metropolis representing one of the most affected areas during the American ZIKV outbreak. We demonstrate rapid spread of ZIKV in Salvador, Brazil, and infection rates exceeding 60%. We provide evidence for the link between ZIKV and microcephaly, report that ZIKV predominantly affects geographic areas with low socioeconomic status, and show that population immunity likely caused cessation of the outbreak. Our results enable stakeholders to identify target populations for vaccination and for trials on vaccine efficacy and allow refocusing of research efforts and intervention strategies

Probing subcellular iron availability with genetically encoded nitric oxide biosensors

Cellular iron supply is required for various biochemical processes. Measuring bioavailable iron in cells aids in obtaining a better understanding of its biochemical activities but is technically challenging. Existing techniques have several constraints that make precise localization difficult, and the lack of a functional readout makes it unclear whether the tested labile iron is available for metalloproteins. Here, we use geNOps; a ferrous iron-dependent genetically encoded fluorescent nitric oxide (NO) biosensor, to measure available iron in cellular locales. We exploited the nitrosylation-dependent fluorescence quenching of geNOps as a direct readout for cellular iron absorption, distribution, and availability. Our findings show that, in addition to ferrous iron salts, the complex of iron (III) with N,N’-bis (2-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid (HBED) can activate the iron (II)-dependent NO probe within intact cells. Cell treatment for only 20 min with iron sucrose was also sufficient to activate the biosensor in the cytosol and mitochondria significantly; however, ferric carboxymaltose failed to functionalize the probe, even after 2 h of cell treatment. Our findings show that the geNOps approach detects available iron (II) in cultured cells and can be applied to assay functional iron (II) at the (sub)cellular level.Vifor Pharm

Kupffer Cells and Blood Monocytes Orchestrate the Clearance of Iron-Carbohydrate Nanoparticles from Serum.

Intravenous (IV) iron nanoparticle preparations are widely used to treat iron deficiency. The mechanism of mononuclear phagocyte system-mediated clearance of IV iron nanoparticles is unknown. The early uptake and homeostasis of iron after injection of ferric carboxymaltose (FCM) in mice was studied. An increase in serum iron was observed at 2.5 h followed by a return to baseline by 24 h. An increase in circulating monocytes was observed, particularly Ly6Chi and Ly6Clow. FCM was also associated with a time-dependent decrease in liver Kupffer cells (KCs) and increase in liver monocytes. The increase in liver monocytes suggests an influx of iron-rich blood monocytes, while some KCs underwent apoptosis. Adoptive transfer experiments demonstrated that following liver infiltration, blood monocytes differentiated to KCs. KCs were also critical for IV iron uptake and biodegradation. Indeed, anti-Colony Stimulating Factor 1 Receptor (CSF1R)-mediated depletion of KCs resulted in elevated serum iron levels and impaired iron uptake by the liver. Gene expression profiling indicated that C-C chemokine receptor type 5 (CCR5) might be involved in monocyte recruitment to the liver, confirmed by pharmaceutical inhibition of CCR5. Liver KCs play a pivotal role in the clearance and storage of IV iron and KCs appear to be supported by the expanded blood monocyte population

Techno-economic analysis of battery storage systems and hydrogen-based storage systems as an alternative to grid expansion in the medium voltage grid in Germany

The decentralization of the energy system in Germany is leading to enormous investments in grid expansion, as the current regulation creates an obligation to expand the power grid to eliminate bottlenecks. Meanwhile, opportunities to leverage grid-friendly control of storage systems are neglected to alleviate the need for investment. For this reason, it is necessary to investigate intelligent alternatives to grid expansion, such as storage systems, to efficiently integrate distributed technologies into the power system and reduce the need for grid expansion. In this work, two representative configurations of a medium voltage grid in Germany are developed for the years 2022 and 2050, and different storage systems are compared economically with the grid expansion in a model-based simulation. Hydrogen storage and battery storage were chosen as storage systems. The results show that grid expansion is the least expensive option if only the grid expansion costs are included in the analysis. However, if additional uses for the storage systems are considered, the battery storage systems are more economical. While in the scenario for 2050 the grid expansion causes costs of approx. 56,000 EUR per year, revenues of at least 58,000 EUR per year can be achieved via the revenue opportunities of the battery storage, representing a 3.5% margin. Heat extraction, arbitrage trading, and avoidance of grid expansion in superimposed grid levels were integrated as additional revenue streams/sources. A robust data basis and cost degressions were assumed for the simulations to generate meaningful results. Overall, hydrogen storage systems are economically inferior to battery storage systems and grid expansion for this use case. The results demonstrate the complexity of analyzing the trade-offs in terms of storage as an alternative to grid expansion as well as the opportunities presented using battery storage instead