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Galactic cosmic rays reach energies of at least a few petaelectronvolts (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators (‘PeVatrons’), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies. Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 1013 electronvolts) were inferred from recent γ-ray observations3. However, none of the currently known accelerators—not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays—has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of γ-rays extending without a cut-off or a spectral break to tens of teraelectronvolts4. Here we report deep γ-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts5and an outflow from the Galactic Centre6. Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 106–107 years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
Major depression is a highly prevalent severe mood disorder that is treated with antidepressants. The molecular targets of antidepressants require definition. We investigated the role of the acid sphingomyelinase (Asm)-ceramide system as a target for antidepressants. Therapeutic concentrations of the antidepressants amitriptyline and fluoxetine reduced Asm activity and ceramide concentrations in the hippocampus, increased neuronal proliferation, maturation and survival and improved behavior in mouse models of stress-induced depression. Genetic Asm deficiency abrogated these effects. Mice overexpressing Asm, heterozygous for acid ceramidase, treated with blockers of ceramide metabolism or directly injected with C16 ceramide in the hippocampus had higher ceramide concentrations and lower rates of neuronal proliferation, maturation and survival compared with controls and showed depression-like behavior even in the absence of stress. The decrease of ceramide abundance achieved by antidepressant-mediated inhibition of Asm normalized these effects. Lowering ceramide abundance may thus be a central goal for the future development of antidepressants.
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.
Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155 304 is analyzed in the high (HE, 100MeV < E < 300 GeV) and very high energy (VHE, E > 200 GeV) gamma-ray domain. Over the course of similar to 9 yr of H. E. S. S. observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index beta(VHE) = 1 .10(+ 0 : 10) (0 : 13)) on timescales larger than one day. An analysis of similar to 5.5 yr of HE Fermi-LAT data gives consistent results (beta(HE) = 1 : 20(+ 0 : 21) (0 : 23), on timescales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior (beta similar to 2) seen on shorter timescales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.
The study investigates the effects of classroom composition (average ability, achievement, and socio-economic background, proportion of immigrant students) on the development in mathematics achievement, and reading literacy from grade 5 to 6. The study draws on a sample of N=1892 students in vocational track schools (Hauptschule) and intermediate track schools (Realschule) in Baden-Wuerttemberg, Germany. After controlling for school type, and between-school differences in student intake characteristics, none of the compositional characteristics showed a statistically significant effect on achievement development. School track was associated with the development of reading literacy even after controlling for individual differences; however, this relationship lost its statistical significance after the composition of the student body was additionally taken into account.
An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of similar to 9 h of on-off observations. Upper limits on the velocity averaged cross section, <sigma upsilon >, for the annihilation of dark matter particles with masses in the range of similar to 300 GeV to similar to 10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of <sigma upsilon > that are larger than 3 x 10(-24) cm(3)/s are excluded for dark matter particles with masses between similar to 1 and similar to 4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on <sigma upsilon > for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.
We report on the formation of wrinkle-patterned surface morphologies in cesium formamidinium-based Cs(x)FA(1-y)Pb(I1-yBry)(3) perovskite compositions with x = 0-0.3 and y = 0-0.3 under various spin-coating conditions. By varying the Cs and Br contents, the perovskite precursor solution concentration and the spin-coating procedure, the occurrence and characteristics of the wrinkle-shaped morphology can be tailored systematically. Cs(0.17)FA(0.83)Pb(I0.83Br0.17)(3) perovskite layers were analyzed regarding their surface roughness, microscopic structure, local and overall composition, and optoelectronic properties. Application of these films in p-i-n perovskite solar cells (PSCs) with indium-doped tin oxide/NiOx/perovskite/C-60/bathocuproine/Cu architecture resulted in up to 15.3 and 17.0% power conversion efficiency for the flat and wrinkled morphology, respectively. Interestingly, we find slightly red-shifted photoluminescence (PL) peaks for wrinkled areas and we are able to directly correlate surface topography with PL peak mapping. This is attributed to differences in the local grain size, whereas there is no indication for compositional demixing in the films. We show that the perovskite composition, crystallization kinetics, and layer thickness strongly influence the formation of wrinkles which is proposed to be related to the release of compressive strain during perovskite crystallization. Our work helps us to better understand film formation and to further improve the efficiency of PSCs with widely used mixed-perovskite compositions.
The present study investigates school context effects on psychosocial characteristics (academic self-concept, peer relations, school satisfaction, and school anxiety) of high-achieving and gifted students. Students who did or did not make an early transition from elementary to secondary schools for high-achieving and gifted students in 5th grade in Berlin, Germany, are compared in their psychosocial development. The sample comprises 155 early-entry students who moved to an academically selective secondary school (Gymnasium) and 3,169 regular students who remained in elementary school until the end of 6th grade. Overall, a complex pattern of psychosocial development emerged for all students, with both positive and negative outcomes being observed. Specifically, the transition into academically selective learning environments seemed to come at some cost for psychosocial development. Propensity score matching analysis isolating the effects of selective school intake and the school context effect itself revealed negative contextual effects of early transition to Gymnasium on academic self-concept and school anxiety; additionally, the positive trend in peer relations observed among regular students was not discernible among early-entry students.
Diffuse gamma-ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeVenergies over several decades, assessments of diffuse gamma-ray emission at TeVenergies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeVenergies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known gamma-ray sources. Corresponding gamma-ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed gamma-ray fluxes show characteristic excess emission not attributable to known gamma-ray sources. For the first time large-scale gamma-ray emission along the Galactic plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved gamma-ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum gamma-ray emission from pi(0) decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic gamma-ray emission and unresolved sources.
This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
Re-observations with the HESS telescope array of the very high-energy (VHE) source HESS J1018-589A that is coincident with the Fermi-LAT gamma-ray binary 1FGL J1018.6-5856 have resulted in a source detection significance of more than 9 sigma and the detection of variability (chi(2)/nu of 238.3/155) in the emitted gamma-ray flux. This variability confirms the association of HESS J1018-589A with the high-energy gamma-ray binary detected Fermi-LAT and also confirms the point-like source as a new VHE binary system. The spectrum of HESS J1018-589A is best fit with a power-law function with photon index Gamma = 2.20 +/- 0.14(stat) +/- 0.2(sys). Emission is detected up to similar to 20 TeV. The mean differential flux level is (2.9 +/- 0.4) x 10(-13) TeV-1 cm(-2) s(-1) at 1 TeV, equivalent to similar to 1% of the flux from the Crab Nebula at the same energy. Variability is clearly detected the night-by-night light curve. When folded on the orbital period of 16.58 days, the rebinned light curve peaks in phase with the observed X-ray high-energy phaseograms. The fit of the HESS phaseogram to a constant flux provides evidence of periodicity at the level of N-sigma > 3 sigma. The of the VHE phaseogram and measured spectrum suggest a low-inclination, low-eccentricity system with a modest impact from VHE gamma-ray due to pair production (tau less than or similar to 1 at 300 GeV).
Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance.
Fontanes Medien
(2023)
Theodor Fontane war, im durchaus modernen Sinne, ein Medienarbeiter: Als Presse-Agent in London lernte er die innovativste Presselandschaft seiner Zeit kennen; als Redakteur in Berlin leistete er journalistische Kärrnerarbeit; er schrieb Kritiken über das Theater, die bildende Kunst und die Literatur – und auch seine Romane wie seine Reisebücher sind stets Medienprodukte, als Serien in in Zeitungen und Zeitschriften platziert, bevor sie auf dem Buchmarkt erschienen.
Der vorliegende Band dokumentiert die Ergebnisse eines internationalen Kongresses, veranstaltet 2019 vom Theodor-Fontane-Archiv in Potsdam. Die ebenso rasante wie umfassende Medialisierung und Vernetzung der Gesellschaft im Laufe des 19. Jahrhunderts wird dabei als produktive Voraussetzung der schriftstellerischen Tätigkeit Fontanes begriffen. Eingebettet in ein weit verzweigtes Netz der Korrespondenz und der postalischen Textzirkulation, vertraut mit den Routinen und Publika der periodischen Massenpresse, für die er sein Leben lang schrieb, und auf vielfältige Weise geprägt von der visuellen Kultur seiner Zeit wird Theodor Fontane als gleichermaßen journalistisch versierter wie ästhetisch sensibler Grenzgänger erkennbar.
Fontanes Medien
(2022)
Theodor Fontane war, im durchaus modernen Sinne, ein Medienarbeiter: Als Presse-Agent in London lernte er die innovativste Presselandschaft seiner Zeit kennen; als Redakteur in Berlin leistete er journalistische Kärrnerarbeit; er schrieb Kritiken über das Theater, die bildende Kunst und die Literatur – und auch seine Romane wie seine Reisebücher sind stets Medienprodukte, als Serien in in Zeitungen und Zeitschriften platziert, bevor sie auf dem Buchmarkt erschienen.
Der vorliegende Band dokumentiert die Ergebnisse eines internationalen Kongresses, veranstaltet 2019 vom Theodor-Fontane-Archiv in Potsdam. Die ebenso rasante wie umfassende Medialisierung und Vernetzung der Gesellschaft im Laufe des 19. Jahrhunderts wird dabei als produktive Voraussetzung der schriftstellerischen Tätigkeit Fontanes begriffen. Eingebettet in ein weit verzweigtes Netz der Korrespondenz und der postalischen Textzirkulation, vertraut mit den Routinen und Publika der periodischen Massenpresse, für die er sein Leben lang schrieb, und auf vielfältige Weise geprägt von der visuellen Kultur seiner Zeit wird Theodor Fontane als gleichermaßen journalistisch versierter wie ästhetisch sensibler Grenzgänger erkennbar.
The poly(A) tail at 3' ends of eukaryotic mRNAs promotes their nuclear export, stability and translational efficiency, and changes in its length can strongly impact gene expression. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerases, PAPS1, PAPS2 and PAPS4. As shown by their different mutant phenotypes, these three isoforms are functionally specialized, with PAPS1 modifying organ growth and suppressing a constitutive immune response. However, the molecular basis of this specialization is largely unknown. Here, we have estimated poly(A)-tail lengths on a transcriptome-wide scale in wild-type and paps1 mutants. This identified categories of genes as particularly strongly affected in paps1 mutants, including genes encoding ribosomal proteins, cell-division factors and major carbohydrate-metabolic proteins. We experimentally verified two novel functions of PAPS1 in ribosome biogenesis and redox homoeostasis that were predicted based on the analysis of poly(A)-tail length changes in paps1 mutants. When overlaying the PAPS1-dependent effects observed here with coexpression analysis based on independent microarray data, the two clusters of transcripts that are most closely coexpressed with PAPS1 show the strongest change in poly(A)-tail length and transcript abundance in paps1 mutants in our analysis. This suggests that their coexpression reflects at least partly the preferential polyadenylation of these transcripts by PAPS1 versus the other two poly(A)-polymerase isoforms. Thus, transcriptome-wide analysis of poly(A)-tail lengths identifies novel biological functions and likely target transcripts for polyadenylation by PAPS1. Data integration with large-scale co-expression data suggests that changes in the relative activities of the isoforms are used as an endogenous mechanism to co-ordinately modulate plant gene expression.
The poly(A) tail at 3’ ends of eukaryotic mRNAs promotes their nuclear export, stability and translational efficiency, and changes in its length can strongly impact gene expression. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerases, PAPS1, PAPS2 and PAPS4. As shown by their different mutant phenotypes, these three isoforms are functionally specialized, with PAPS1 modifying organ growth and suppressing a constitutive immune response. However, the molecular basis of this specialization is largely unknown. Here, we have estimated poly(A)-tail lengths on a transcriptome-wide scale in wild-type and paps1 mutants. This identified categories of genes as particularly strongly affected in paps1 mutants, including genes encoding ribosomal proteins, cell-division factors and major carbohydrate-metabolic proteins. We experimentally verified two novel functions of PAPS1 in ribosome biogenesis and redox homoeostasis that were predicted based on the analysis of poly(A)-tail length changes in paps1 mutants. When overlaying the PAPS1-dependent effects observed here with coexpression analysis based on independent microarray data, the two clusters of transcripts that are most closely coexpressed with PAPS1 show the strongest change in poly(A)-tail length and transcript abundance in paps1 mutants in our analysis. This suggests that their coexpression reflects at least partly the preferential polyadenylation of these transcripts by PAPS1 versus the other two poly(A)-polymerase isoforms. Thus, transcriptome-wide analysis of poly(A)-tail lengths identifies novel biological functions and likely target transcripts for polyadenylation by PAPS1. Data integration with large-scale co-expression data suggests that changes in the relative activities of the isoforms are used as an endogenous mechanism to co-ordinately modulate plant gene expression.
The poly(A) tail at 3’ ends of eukaryotic mRNAs promotes their nuclear export, stability and translational efficiency, and changes in its length can strongly impact gene expression. The Arabidopsis thaliana genome encodes three canonical nuclear poly(A) polymerases, PAPS1, PAPS2 and PAPS4. As shown by their different mutant phenotypes, these three isoforms are functionally specialized, with PAPS1 modifying organ growth and suppressing a constitutive immune response. However, the molecular basis of this specialization is largely unknown. Here, we have estimated poly(A)-tail lengths on a transcriptome-wide scale in wild-type and paps1 mutants. This identified categories of genes as particularly strongly affected in paps1 mutants, including genes encoding ribosomal proteins, cell-division factors and major carbohydrate-metabolic proteins. We experimentally verified two novel functions of PAPS1 in ribosome biogenesis and redox homoeostasis that were predicted based on the analysis of poly(A)-tail length changes in paps1 mutants. When overlaying the PAPS1-dependent effects observed here with coexpression analysis based on independent microarray data, the two clusters of transcripts that are most closely coexpressed with PAPS1 show the strongest change in poly(A)-tail length and transcript abundance in paps1 mutants in our analysis. This suggests that their coexpression reflects at least partly the preferential polyadenylation of these transcripts by PAPS1 versus the other two poly(A)-polymerase isoforms. Thus, transcriptome-wide analysis of poly(A)-tail lengths identifies novel biological functions and likely target transcripts for polyadenylation by PAPS1. Data integration with large-scale co-expression data suggests that changes in the relative activities of the isoforms are used as an endogenous mechanism to co-ordinately modulate plant gene expression.
GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
G349.7+0.2 is a young Galactic supernova remnant (SNR) located at the distance of 11.5 kpc and observed across the entire electromagnetic spectrum from radio to high energy (HE; 0.1 GeV < E < 100 GeV) gamma-rays. Radio and infrared observations indicate that the remnant is interacting with a molecular cloud. In this paper, the detection of very high energy (VHE, E > 100 GeV) gamma-ray emission coincident with this SNR with the High Energy Stereoscopic System (HESS.) is reported. This makes it one of the farthest Galactic SNR ever detected in this domain. An integral flux F(E > 400 GeV) = (6.5 +/- 1.1(stat) +/- 1.3(syst)) x 10-11 ph cm(-2) s(-1) corresponding to similar to 0.7% of that of the Crab Nebula and to a luminosity of similar to 10(34) erg s(-1) above the same energy threshold, and a steep photon index Gamma(VHE) = 2.8 +/- 0.27(stat) +/- 0.20(syst) are measured. The analysis of more than 5 yr of Fermi-LAT data towards this source shows a power-law like spectrum with a best-fit photon index Gamma(HE) = 2.2 +/- 0.04.2(stat-0.31sys)(+0.13), The combined gamma-ray spectrum of 0349.7+0.2 can be described by either a broken power law (I3PL) or a power law with exponential (or sub exponential) cutoff (PLC). In the former case, the photon break energy is found at E-br,E-gamma = 551(-30)(+70) GeV, slightly higher than what is usually observed in the HE/VHE gamma-ray emitting middle-aged SNRs known to be interacting with molecular clouds. In the latter case. the exponential (respectively sub-exponential) cutoff energy is measured at E-cat,E-gamma = 1.4(-0.55)(+1.6) (respectively 0.35(-0.21)(+0.75)) TeV. A pion decay process resulting from the interaction of the accelerated protons and nuclei with the dense surrounding medium is clearly the preferred scenario to explain the gamma-ray emission. The BPL with a spectral steepening of 0.5-1 and the PLC provide equally good fits to the data. The product or the average gas density and the total energy content of accelerated protons and nuclei amounts to nu W-p similar to 5 x 10(51) erg cm(-3)
HESS J1640-465 - an exceptionally luminous TeV gamma-ray supernova remnant (vol 439, pg 2828, 2014)
(2014)
The results of follow-up observations of the TeV gamma-ray source HESS J1640-465 from 2004 to 2011 with the High Energy Stereoscopic System (HESS) are reported in this work. The spectrum is well described by an exponential cut-off power law with photon index Gamma = 2.11 +/- 0.09(stat) +/- 0.10(sys), and a cut-off energy of E-2 = 6.0(-1.2)(+2.0) TeV. The TeV emission is significantly extended and overlaps with the northwestern part of the shell of the SNR G338.3-0.0. The new HESS results, a re-analysis of archival XMM-Newton data and multiwavelength observations suggest that a significant part of the gamma-ray emission from HESS J1640-465 originates in the supernova remnant shell. In a hadronic scenario, as suggested by the smooth connection of the GeV and TeV spectra, the product of total proton energy and mean target density could be as high as W(p)n(H) similar to 4 x 10(52)(d/10kpc)(2) erg cm(-3).
A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l = -1.5 degrees, b = 0 degrees and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. results. No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.
Context. Puppis A is an interesting similar to 4 kyr-old supernova remnant (SNR) that shows strong evidence of interaction between the forward shock and a molecular cloud. It has been studied in detail from radio frequencies to high-energy (HE, 0.1-100 GeV) gamma-rays. An analysis of the Fermi-LAT data has shown extended HE gamma-ray emission with a 0.2-100 GeV spectrum exhibiting no significant deviation from a power law, unlike most of the GeV-emitting SNRs known to be interacting with molecular clouds. This makes it a promising target for imaging atmospheric Cherenkov telescopes (IACTs) to probe the gamma-ray emission above 100 GeV.
Aims. Very-high-energy (VHE, E >= 0.1 TeV) gamma-ray emission from Puppis A has been, for the first time, searched for with the High Energy Stereoscopic System (HESS.).
Methods. Stereoscopic imaging of Cherenkov radiation from extensive air showers is used to reconstruct the direction and energy of the incident gamma-rays in order to produce sky images and source spectra. The profile likelihood method is applied to find constraints on the existence of a potential break or cutoff in the photon spectrum.
Results. The analysis of the HESS. data does not reveal any significant emission towards Puppis A. The derived upper limits on the differential photon flux imply that its broadband gamma-ray spectrum must exhibit a spectral break or cutoff. By combining Fermi-LAT and HESS. measurements, the 99% confidence-level upper limits on such a cutoff are found to be 450 and 280 GeV, assuming a power law with a simple exponential and a sub-exponential cutoff, respectively. It is concluded that none of the standard limitations (age, size, radiative losses) on the particle acceleration mechanism, assumed to be continuing at present, can explain the lack of VHE signal. The scenario in which particle acceleration has ceased some time ago is considered as an alternative explanation. The HE/VHE spectrum of Puppis A could then exhibit a break of non-radiative origin (as observed in several other interacting SNRs, albeit at somewhat higher energies), owing to the interaction with dense and neutral material, in particular towards the NE region.
The incorporation of even small amounts of strontium (Sr) into lead-base hybrid quadruple cation perovskite solar cells results in a systematic increase of the open circuit voltage (V-oc) in pin-type perovskite solar cells. We demonstrate via absolute and transient photoluminescence (PL) experiments how the incorporation of Sr significantly reduces the non-radiative recombination losses in the neat perovskite layer. We show that Sr segregates at the perovskite surface, where it induces important changes of morphology and energetics. Notably, the Sr-enriched surface exhibits a wider band gap and a more n-type character, accompanied with significantly stronger surface band bending. As a result, we observe a significant increase of the quasi-Fermi level splitting in the neat perovskite by reduced surface recombination and more importantly, a strong reduction of losses attributed to non-radiative recombination at the interface to the C-60 electron-transporting layer. The resulting solar cells exhibited a V-oc of 1.18 V, which could be further improved to nearly 1.23 V through addition of a thin polymer interlayer, reducing the non-radiative voltage loss to only 110 meV. Our work shows that simply adding a small amount of Sr to the precursor solutions induces a beneficial surface modification in the perovskite, without requiring any post treatment, resulting in high efficiency solar cells with power conversion efficiency (PCE) up to 20.3%. Our results demonstrate very high V-oc values and efficiencies in Sr-containing quadruple cation perovskite pin-type solar cells and highlight the imperative importance of addressing and minimizing the recombination losses at the interface between perovskite and charge transporting layer.
This longitudinal study of N = 1,566 adolescents investigated the protective role of optimism in adjustment to parental separation, focusing on two salient challenges faced by adolescents, namely academic achievement and self-esteem. Based on latent change models, the results indicated associations between parental separation and short-term declines in academic achievement as well as short-term and longer term declines in self-esteem. Although optimism in general showed positive associations with academic achievement and self-esteem, its role as a protective factor proved to be particularly important for academic achievement in adjustment following parental separation.
This longitudinal study of N = 1,566 adolescents investigated the protective role of optimism in adjustment to parental separation, focusing on two salient challenges faced by adolescents, namely academic achievement and self-esteem. Based on latent change models, the results indicated associations between parental separation and short-term declines in academic achievement as well as short-term and longer term declines in self-esteem. Although optimism in general showed positive associations with academic achievement and self-esteem, its role as a protective factor proved to be particularly important for academic achievement in adjustment following parental separation.
The implementation of shape-memory effects (SME) in polymeric micro- or nano-objects currently relies on the application of indirect macroscopic manipulation techniques, for example, stretchable molds or phantoms, to ensembles of small objects. Here, we introduce a method capable of the controlled manipulation and SME quantification of individual micro- and nano-objects in analogy to macroscopic thermomechanical test procedures. An atomic force microscope was utilized to address individual electro-spun poly(ether urethane) (PEU) micro- or nanowires freely suspended between two micropillars on a micro-structured silicon substrate. In this way, programming strains of 10 +/- 1% or 21 +/- 1% were realized, which could be successfully fixed. An almost complete restoration of the original free-suspended shape during heating confirmed the excellent shape-memory performance of the PEU wires. Apparent recovery stresses of sigma(max,app)=1.2 +/- 0.1 and 33.3 +/- 0.1MPa were obtained for a single microwire and nanowire, respectively. The universal AFM test platform described here enables the implementation and quantification of a thermomechanically induced function for individual polymeric micro- and nanosystems.
In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
Measurement of the EBL spectral energy distribution using the VHE gamma-ray spectra of HESS blazars
(2017)
Very high-energy gamma rays (VHE, E greater than or similar to 100 GeV) propagating over cosmological distances can interact with the low-energy photons of the extragalactic background light (EBL) and produce electron-positron pairs. The transparency of the Universe to VHE gamma rays is then directly related to the spectral energy distribution (SED) of the EBL. The observation of features in the VHE energy spectra of extragalactic sources allows the EBL to be measured, which otherwise is very difficult. An EBL model-independent measurement of the EBL SED with the H.E.S.S. array of Cherenkov telescopes is presented. It was obtained by extracting the EBL absorption signal from the reanalysis of high-quality spectra of blazars. From H.E.S.S. data alone the EBL signature is detected at a significance of 9.5 sigma, and the intensity of the EBL obtained in different spectral bands is presented together with the associated gamma-ray horizon.
Personality is a relevant predictor for important life outcomes across the entire lifespan. Although previous studies have suggested the comparability of the measurement of the Big Five personality traits across adulthood, the generalizability to childhood is largely unknown. The present study investigated the structure of the Big Five personality traits assessed with the Big Five Inventory-SOEP Version (BFI-S; SOEP = Socio-Economic Panel) across a broad age range spanning 11-84 years. We used two samples of N = 1,090 children (52% female, M-age = 11.87) and N = 18,789 adults (53% female, M-age = 51.09), estimating a multigroup CFA analysis across four age groups (late childhood: 11-14 years; early adulthood: 17-30 years; middle adulthood: 31-60 years; late adulthood: 61-84 years). Our results indicated the comparability of the personality trait metric in terms of general factor structure, loading patterns, and the majority of intercepts across all age groups. Therefore, the findings suggest both a reliable assessment of the Big Five personality traits with the BFI-S even in late childhood and a vastly comparable metric across age groups.
Equally able students have lower academic self-concepts in high-achieving classrooms than in low-achieving classrooms. This highly general and robust frame of reference effect is widely known as the Big-Fish-Little-Pond Effect (BFLPE; Marsh, 1987). This study contributes to research aiming to identify moderators of the BFLPE by investigating the effects of students' personality (i.e. Big Five traits and narcissism). Multilevel structural equation modeling was used to test the moderator hypotheses, drawing on data from a large sample of N= 4973 upper secondary track students (M age = 19.57). Consistent with a priori predictions, the negative effect of school-average achievement (the BFLPE) interacted significantly with narcissism. Students high in narcissism experienced smaller BFLPEs than did students with low or average levels of narcissism. The statistically significant effect for neuroticism acted in the opposite direction. The study illustrates how personality moderates frame of reference effects that are central to self-concept formation.
Die Sekundarstufe ist gekennzeichnet durch eine Sequenz von Übergängen, an denen Ungleichheiten durch Leistungsdisparitäten (primäre Effekte) und Bildungsentscheidungen (sekundäre Effekte) nach sozialer Herkunft relevant werden. Diese Herkunftseffekte werden mit dem vorliegenden Beitrag erstmals anhand von Daten einer vollständigen Schülerkohorte (Hamburger KESS-Studie) über den gesamten Verlauf der Sekundarstufe vom Übergang ins Gymnasium bis zur Studienintention analysiert. Eine Dekomposition und Quantifizierung primärer und sekundärer Effekte mit der KHB-Methode erfolgt dabei erstmals auch für den Eintritt in die Oberstufe. Abnehmende absolute Herkunftseffekte über den Bildungsverlauf, auf die bisherige Befunde verschiedener Stichproben verweisen, können mit dieser Studie zum Teil bestätigt werden. Zum vermuteten relativen Bedeutungszuwachs sekundärer Effekte zeigen die Ergebnisse kein eindeutiges Muster: Beim Wechsel ins Gymnasium überwiegen primäre Effekte leicht, wenn Noten als Leistungsindikator verwendet werden. Beim Eintritt in die Oberstufe bleibt die Relation nahezu unverändert. Erst bei der Studienintention fällt die relative Bedeutung sekundärer Effekte größer aus.
Aims. Previous observations with the High Energy Stereoscopic System (H.E.S.S.) have revealed an extended very-high-energy (VHE; E > 100 GeV) gamma-ray source, HESS J1834-087, coincident with the supernova remnant (SNR) W41. The origin of the gamma-ray emission was investigated in more detail with the H.E.S.S. array and the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope.
Methods. The gamma-ray data provided by 61 h of observations with H.E.S.S., and four years with the Fermi LAT were analyzed, covering over five decades in energy from 1.8 GeV up to 30 TeV. The morphology and spectrum of the TeV and GeV sources were studied and multiwavelength data were used to investigate the origin of the gamma-ray emission toward W41.
Results. The TeV source can be modeled with a sum of two components: one point-like and one significantly extended (sigma(TeV) = 0.17 degrees +/- 0.01 degrees), both centered on SNR W41 and exhibiting spectra described by a power law with index Gamma(TeV) similar or equal to 2.6. The GeV source detected with Fermi LAT is extended (sigma(GeV) = 0.15 degrees +/- 0.03 degrees) and morphologically matches the VHE emission. Its spectrum can be described by a power-law model with an index Gamma(GeV) = 2.15 +/- 0.12 and smoothly joins the spectrum of the whole TeV source. A break appears in the gamma-ray spectra around 100 GeV. No pulsations were found in the GeV range.
Conclusions. Two main scenarios are proposed to explain the observed emission: a pulsar wind nebula (PWN) or the interaction of SNR W41 with an associated molecular cloud. X-ray observations suggest the presence of a point-like source (a pulsar candidate) near the center of the remnant and nonthermal X-ray diffuse emission that could arise from the possibly associated PWN. The PWN scenario is supported by the compatible positions of the TeV and GeV sources with the putative pulsar. However, the spectral energy distribution from radio to gamma-rays is reproduced by a one-zone leptonic model only if an excess of low-energy electrons is injected following a Maxwellian distribution by a pulsar with a high spin-down power (> 10(37) erg s(-1)). This additional low-energy component is not needed if we consider that the point-like TeV source is unrelated to the extended GeV and TeV sources. The interacting SNR scenario is supported by the spatial coincidence between the gamma-ray sources, the detection of OH (1720 MHz) maser lines, and the hadronic modeling.
Background. Assigning students to different school tracks on the basis of their achievement levels is a widely used strategy that aims at giving students the best possible learning opportunity. There is, however, a growing body of literature that questions such positive effects of tracking. Aims. This study compared the developmental trajectories of reading comprehension and decoding speed between students at academic track schools that typically prepare students for university entrance and students at non-academic track schools that usually prepare students for vocational education. Sample. In a longitudinal design with three occasions of data collection, the authors drew on a sample of N= 1,508 5th graders (age at T1 about 11 years, age at T3 about 14 years) from 60 schools in Germany. The academic track sample comprised n= 568 students; the non-academic track sample comprised n= 940 students. Method. Achievement measures were obtained by standardized tests of reading comprehension and decoding speed. Students at the different tracks were closely matched using propensity scores. To compare students growth trajectories between the different school tracks, we applied multi-group latent growth curve models. Results. Comparable results were recorded for the complete (unmatched) sample and for the matched pairs. In all cases, students at the different tracks displayed a similar growth in reading comprehension, whereas larger growth rates for students at academic track schools were recorded for decoding speed. Conclusions. Our findings contribute to an increasing body of literature suggesting that tracking might have undesired side effects.
Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of 51 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C-16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing 1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis.
Search for dark matter annihilation signatures in HESS observations of
dwarf spheroidal galaxies
(2014)
Dwarf spheroidal galaxies of the Local Group are close satellites of the Milky Way characterized by a large mass-to-light ratio and are not expected to be the site of nonthermal high-energy gamma-ray emission or intense star formation. Therefore they are among the most promising candidates for indirect dark matter searches. During the last years the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes observed five of these dwarf galaxies for more than 140 hours in total, searching for TeV gamma-ray emission from annihilation of dark matter particles. The new results of the deep exposure of the Sagittarius dwarf spheroidal galaxy, the first observations of the Coma Berenices and Fornax dwarves and the reanalysis of two more dwarf spheroidal galaxies already published by the H.E.S.S. Collaboration, Carina and Sculptor, are presented. In the absence of a significant signal new constraints on the annihilation cross section applicable to weakly interacting massive particles (WIMPs) are derived by combining the observations of the five dwarf galaxies. The combined exclusion limit depends on the WIMP mass and the best constraint is reached at 1-2 TeV masses with a cross-section upper bound of similar to 3.9 x 10(-24) cm(3) s(-1) at a 95% confidence level.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
Context. Very-high-energy (VHE; E > 100 GeV) gamma-ray emission from blazars inevitably gives rise to electron-positron pair production through the interaction of these gamma-rays with the extragalactic background light (EBL). Depending on the magnetic fields in the proximity of the source, the cascade initiated from pair production can result in either an isotropic halo around an initially- beamed source or a magnetically- broadened cascade :aux.
Aims. Both extended pair-halo (PH) and magnetically broadened cascade (MBC) emission from regions surrounding the blazars 1ES 1101-232, IRS 0229+200, and PKS 2155-304 were searched for using VHE y-ray data taken with the High Energy Stereoscopic System (HESS.) and high-energy (HE; 100 MeV < E < 100 GeV) gamma-ray data with the Fermi Large Area Telescope (LAT).
Methods. By comparing the angular distributions of the reconstructed gamma-ray events to the angular profiles calculated from detailed theoretical models, the presence of PH and MBC was investigated.
Results. Upper limits on the extended emission around lES 1101-232, lES 0229+200, and PKS 2155-304 are found to be at a level of a few per cent of the Crab nebula flux above 1 TeV, depending on the assumed photon index of the cascade emission. Assuming strong extra-Galactic magnetic field (EGME) values, >10(-12) G, this limits the production of pair haloes developing from electromagnetic cascades. For weaker magnetic fields, in which electromagnetic cascades would result in MBCs. EGMF strengths in the range (0.3-3) x 10(-15) G were excluded for PKS 2155-304 at the 99% confidence level, under the assumption of a 1 Mpc coherence length.
Dwarf spheroidal galaxies are among the most promising targets for detecting signals of Dark Matter (DM) annihilations. The H.E.S.S. experiment has observed five of these systems for a total of about 130 hours. The data are re-analyzed here, and, in the absence of any detected signals, are interpreted in terms of limits on the DM annihilation cross section. Two scenarios are considered: i) DM annihilation into mono-energetic gamma-rays and ii) DM in the form of pure WIMP multiplets that, annihilating into all electroweak bosons, produce a distinctive gamma-ray spectral shape with a high-energy peak at the DM mass and a lower-energy continuum. For case i), upper limits at 95% confidence level of about <sigma upsilon > less than or similar to 3 x 10(-25) cm(3) s(-1) are obtained in the mass range of 400 GeV to 1TeV. For case ii), the full spectral shape of the models is used and several excluded regions are identified, but the thermal masses of the candidates are not robustly ruled out.
Das 3. Herbsttreffen Patholinguistik fand am 21. November 2009 an der Universität Potsdam statt. Der vorliegende Tagungsband enthält die drei Hauptvorträge zum Schwerpunktthema „Von der Programmierung zu Artikulation: Sprechapraxie bei Kindern und Erwachsenen“. Darüber hinaus enthält der Band die Beiträge aus dem Spektrum Patholinguistik, sowie die Abstracts der Posterpräsentationen.
Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P.aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P.aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection.
Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients. The increase in ceramide mediates an ectopic expression of beta 1-integrins in the luminal membrane of CF epithelial cells, which results, via an unknown mechanism, in a down-regulation of acid ceramidase. It is predominantly this down-regulation of acid ceramidase that results in the imbalance of ceramide and sphingosine in CF cells. Correction of ceramide and sphingosine levels can be achieved by inhalation of functional acid sphingomyelinase inhibitors, recombinant acid ceramidase or by normalization of beta 1-integrin expression and subsequent re-expression of endogenous acid ceramidase. These treatments correct pulmonary inflammation and prevent or treat, respectively, acute and chronic pulmonary infections in CF mice with Staphylococcus aureus and mucoid or non-mucoid Pseudomonas aeruginosa. Inhalation of sphingosine corrects sphingosine levels only and seems to mainly act against the infection. Many antidepressants are functional inhibitors of the acid sphingomyelinase and were designed for systemic treatment of major depression. These drugs could be repurposed to treat CF by inhalation.
Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in critically ill patients. Here, we employed the broad antibacterial effects of sphingosine to prevent VAP by developing a novel method of coating surfaces of endotracheal tubes with sphingosine and sphingosine analogs. Sphingosine and phytosphingosine coatings of endotracheal tubes prevent adherence and mediate killing of Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus, even in biofilms. Most importantly, sphingosine-coating of endotracheal tubes also prevented P. aeruginosa and S. aureus pneumonia in vivo. Coating of the tubes with sphingosine was stable, without obvious side effects on tracheal epithelial cells and did not induce inflammation. In summary, we describe a novel method to coat plastic surfaces and provide evidence for the application of sphingosine and phytosphingosine as novel antimicrobial coatings to prevent bacterial adherence and induce killing of pathogens on the surface of endotracheal tubes with potential to prevent biofilm formation and VAP.Key messagesNovel dip-coating method to coat plastic surfaces with lipids.Sphingosine and phytosphingosine as novel antimicrobial coatings on plastic surface.Sphingosine coatings of endotracheal tubes prevent bacterial adherence and biofilms.Sphingosine coatings of endotracheal tubes induce killing of pathogens.Sphingosine coatings of endotracheal tubes ventilator-associated pneumonia.
Background: Functional abdominal pain (FAP) is not only a highly prevalent disease but also poses a considerable burden on children and their families. Untreated, FAP is highly persistent until adulthood, also leading to an increased risk of psychiatric disorders. Intervention studies underscore the efficacy of cognitive behavioral treatment approaches but are limited in terms of sample size, long-term follow-up data, controls and inclusion of psychosocial outcome data.
Methods/Design: In a multicenter randomized controlled trial, 112 children aged 7 to 12 years who fulfill the Rome III criteria for FAP will be allocated to an established cognitive behavioral training program for children with FAP (n = 56) or to an active control group (focusing on age-appropriate information delivery; n = 56). Randomization occurs centrally, blockwise and is stratified by center. This study is performed in five pediatric gastroenterology outpatient departments. Observer-blind assessments of outcome variables take place four times: pre-, post-, 3- and 12-months post-treatment. Primary outcome is the course of pain intensity and frequency. Secondary endpoints are health-related quality of life, pain-related coping and cognitions, as well as selfefficacy.
Discussion: This confirmatory randomized controlled clinical trial evaluates the efficacy of a cognitive behavioral intervention for children with FAP. By applying an active control group, time and attention processes can be controlled, and long-term follow-up data over the course of one year can be explored.
Background: Functional abdominal pain (FAP) is not only a highly prevalent disease but also poses a considerable burden on children and their families. Untreated, FAP is highly persistent until adulthood, also leading to an increased risk of psychiatric disorders. Intervention studies underscore the efficacy of cognitive behavioral treatment approaches but are limited in terms of sample size, long-term follow-up data, controls and inclusion of psychosocial outcome data.
Methods/Design: In a multicenter randomized controlled trial, 112 children aged 7 to 12 years who fulfill the Rome III criteria for FAP will be allocated to an established cognitive behavioral training program for children with FAP (n = 56) or to an active control group (focusing on age-appropriate information delivery; n = 56). Randomization occurs centrally, blockwise and is stratified by center. This study is performed in five pediatric gastroenterology outpatient departments. Observer-blind assessments of outcome variables take place four times: pre-, post-, 3- and 12-months post-treatment. Primary outcome is the course of pain intensity and frequency. Secondary endpoints are health-related quality of life, pain-related coping and cognitions, as well as selfefficacy.
Discussion: This confirmatory randomized controlled clinical trial evaluates the efficacy of a cognitive behavioral intervention for children with FAP. By applying an active control group, time and attention processes can be controlled, and long-term follow-up data over the course of one year can be explored.