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Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.
Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation.
Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.
Conclusions: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.
We present the measured correlation functions for pi+ pi-, pi- pi- and pi+ pi+ pairs in central S+Ag collisions at 200 GeV per nucleon. The Gamov function, which has been traditionally used to correct the correlation functions of charged pions for the Coulomb interaction, is found to be inconsistent with all measured correlation functions. Certain problems which have been dominating the systematic uncertainty of the correlation analysis are related to this inconsistency. It is demonstrated that a new Coulomb correction method, based exclusively on the measured correlation function for pi+ pi- pairs, may solve the problem.
The NA35 experiment has collected a high statistics set of momentum analyzed negative hadrons near and forward of midrapidity for central collisions of 200A GeV/c 32S+S, Cu, Ag, and Au. Using momentum space correlations to study the size of the source of particle production, the transverse source radii are found to decrease by ~40% at midrapidity and ~20% at forward rapidity while the longitudinal radius RL is found to decrease by ~50% as pT increases over the interval 50<pT<600 MeV/c. Calculations using a microscopic phase space approach (relativistic quantum molecular dynamics) reproduce the observed trends of the data. PACS: 25.75.+r
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
The international research project RECONCILE has addressed central questions regarding polar ozone depletion, with the objective to quantify some of the most relevant yet still uncertain physical and chemical processes and thereby improve prognostic modelling capabilities to realistically predict the response of the ozone layer to climate change. This overview paper outlines the scope and the general approach of RECONCILE, and it provides a summary of observations and modelling in 2010 and 2011 that have generated an in many respects unprecedented dataset to study processes in the Arctic winter stratosphere. Principally, it summarises important outcomes of RECONCILE including (i) better constraints and enhanced consistency on the set of parameters governing catalytic ozone destruction cycles, (ii) a better understanding of the role of cold binary aerosols in heterogeneous chlorine activation, (iii) an improved scheme of polar stratospheric cloud (PSC) processes that includes heterogeneous nucleation of nitric acid trihydrate (NAT) and ice on non-volatile background aerosol leading to better model parameterisations with respect to denitrification, and (iv) long transient simulations with a chemistry-climate model (CCM) updated based on the results of RECONCILE that better reproduce past ozone trends in Antarctica and are deemed to produce more reliable predictions of future ozone trends. The process studies and the global simulations conducted in RECONCILE show that in the Arctic, ozone depletion uncertainties in the chemical and microphysical processes are now clearly smaller than the sensitivity to dynamic variability.
MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy
(2014)
Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Experimental study of the ¹⁵O(2p,γ)¹⁷Ne cross section by Coulomb dissociation for the rp process
(2016)
The time-reversed reaction 15O(2p, γ)17Ne has been studied by the Coulomb dissociation technique. Secondary 17Ne ion beams at 500 AMeV have been produced by fragmentation reactions of 20Ne in a beryllium production target and dissociated on a secondary Pb target. The incoming beam and the reaction products have been identified with the kinematically complete LAND-R3B experimental setup at GSI. The excitation energy prior to decay has been reconstructed by using the invariant-mass method. The preliminary differential and integral Coulomb Dissociation cross sections (σCoul) have been calculated, which provide a photoabsorption (σphoto) and a radiative capture cross section (σcap). Additionally, important information about the nuclear structure of the 17Ne nucleus will be obtained. The analysis is in progress.
We have studied one-proton-removal reactions of about 500MeV/u 17Ne beams on a carbon target at the R3B/LAND setup at GSI by detecting beam-like 15O-p and determining their relative-energy distribution. We exclusively selected the removal of a 17Ne halo proton, and the Glauber-model analysis of the 16F momentum distribution resulted in an s2 contribution in the 17Ne ground state of about 40%.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).
We report on a polarization measurement of inclusive J/ψ mesons in the di-electron decay channel at mid-rapidity at 2 < pT < 6 GeV/c in p + p collisions at √s = 200 GeV. Data were taken with the STAR detector at RHIC. The J/ψ polarization measurement should help to distinguish between different models of the J/ψ production mechanism since they predict different pT dependences of the J/ψ polarization. In this analysis, J/ψ polarization is studied in the helicity frame. The polarization parameter λθ measured at RHIC becomes smaller towards high pT , indicating more longitudinal J/ψ polarization as pT increases. The result is compared with predictions of presently available models.
Hypomethylating agents decitabine and azacytidine are regarded as interchangeable in the treatment of acute myeloid leukemia (AML). However, their mechanisms of action remain incompletely understood, and predictive biomarkers for HMA efficacy are lacking. Here, we show that the bioactive metabolite decitabine triphosphate, but not azacytidine triphosphate, functions as activator and substrate of the triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation. Retrospective immunohistochemical analysis of bone marrow specimens from AML patients at diagnosis revealed that SAMHD1 expression in leukemic cells inversely correlates with clinical response to decitabine, but not to azacytidine. SAMHD1 ablation increases the antileukemic activity of decitabine in AML cell lines, primary leukemic blasts, and xenograft models. AML cells acquire resistance to decitabine partly by SAMHD1 up-regulation. Together, our data suggest that SAMHD1 is a biomarker for the stratified use of hypomethylating agents in AML patients and a potential target for the treatment of decitabine-resistant leukemia.
The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers (‘average reader’) was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Background: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine.
Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate.
Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery.
Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy.
We present a measurement of e+e− pair production in central PbAu collisions at 158A GeV/c. As reported earlier, a significant excess of the e+e− pair yield over the expectation from hadron decays is observed. The improved mass resolution of the present data set, recorded with the upgraded CERES experiment at the CERN-SPS, allows for a comparison of the data with different theoretical approaches. The data clearly favor a substantial in-medium broadening of the ρ spectral function over a density-dependent shift of the ρ pole mass. The in-medium broadening model implies that baryon induced interactions are the key mechanism to the observed modifications of the ρ meson at SPS energy.
Rezensionen [2018]
(2018)
Verzeichnis
Einzelrezensionen
154 Beauvais, Clémentine: The Mighty Child. Time and Power in Children’s Literature (Thomas Kullmann)
155 Dean-Ruzicka, Rachel: Tolerance Discourse and Young Adult Holocaust Literature. Engaging Difference and Identity (Susanne Blumesberger)
157 Dolle-Weinkauff, Bernd (Hrsg.): Geschichte im Comic. Befunde – Theorien – Erzählweisen (Caroline Wittig)
159 Ewers, Hans-Heino (Hrsg.): Erster Weltkrieg: Kindheit, Jugend und Literatur. Deutschland, Österreich, Osteuropa, England, Belgien und Frankreich (Kurt Franz)
161 Franz, Kurt / Lange, Günter (Hrsg.): Der Stoff, aus dem Geschichten sind. Intertextualität im Werk Otfried Preußlers (sabine fuchs)
163 Glasenapp, Gabriele von/Kagelmann, Andre/Giesa, Felix (Hrsg.): Die Zeitalter werden besichtigt. Aktuelle Tendenzen der Kinder- und Jugendliteraturforschung. Festschrift für Otto Brunken (Karin Richter)
165 Josting, Petra/Schmideler, Sebastian (Hrsg.): Bonsels’ Tierleben. Insekten und Kriechtiere in Kinder- und Jugendmedien (Kurt Franz)
167 Kriegleder, Wynfrid/ Lexe, Heidi / Loidl, Sonja/ Seibert, Ernst (Hrsg.): Jugendliteratur im Kontext von Jugendkultur (Lena Hoffmann)
169 Kurwinkel, Tobias: Bilderbuchanalyse. Narrativik – Ästhetik – Didaktik (Annette Kliewer)
171 Langenhorst, Georg/Naurath, Elisabeth (Hrsg.): Kindertora – Kinderbibel – Kinderkoran. Neue Chancen für (inter-)religiöses Lernen (Renate Grubert)
172 Lathey, Gillian: Translating Children’s Literature (heike Elisabeth Jüngst)
174 Mairbäurl, Gunda/Seibert, Ernst (Hrsg.): Kulturelle Austauschprozesse in der Kinder- und Jugendliteratur. Zur genrespezifischen Transformation von Themen, Stoffen und Motiven im medialen Kontext (Sarah Terhorst)
176 Maiwald, Klaus /Meyer, Anna-Maria/Pecher, Claudia Maria (Hrsg.): »Klassiker« des Kinderund Jugendfilms (Michael Stierstorfer)
177 Mills, Claudia (Hrsg.): Ethics in Children’s Literature (Thomas Kullmann)
179 Nast, Mirjam: »Perry Rhodan« lesen. Zur Serialität der Lektürepraktiken einer Heftromanserie (Wolfgang Biesterfeld)
181 O’Sullivan, Emer / Immel, Andrea (Hrsg.): Imagining Sameness and Difference in Children’s Literature. From the Enlightenment to the Present Day (Iris Schäfer)
182 Oetken, Mareile: Wie Bilderbücher erzählen. Analysen multimodaler Strukturen und bimedialen Erzählens im Bilderbuch (Katharina Egerer)
184 Schmideler, Sebastian (Hrsg.): Wissensvermittlung in der Kinder- und Jugendliteratur der DDR. Themen, Formen, Strukturen, Illustrationen (Sabine Planka)
186 Standke, Jan (Hrsg.): Wolfgang Herrndorf lesen. Beiträge zur Didaktik der deutschsprachigen Gegenwartsliteratur (Sabine Planka)
187 Viel, Bernhard: Der Honigsammler. Waldemar Bonsels, Vater der Biene Maja. Eine Biografie (Renate Grubert)
189 Zellerhoff, Rita: Komplexe sprachliche Strukturen in der Jugendliteratur. Aufgezeigt an Beispielen preisgekrönter Werke der Jugendjury des Deutschen Jugendliteraturpreises (Susanne Riegler)
Sammelrezensionen
191 Anker, Martin u.a. (Hrsg.): Grimms Märchenwelten im Bilderbuch. Beiträge zur Entwicklung des Märchenbilderbuches seit Mitte des 20. Jahrhunderts. – Brinker-von der Heyde, Claudia u. a. (Hrsg.): Märchen, Mythen und Moderne. 200 Jahre Kinder- und Hausmärchen der Brüder Grimm. – Joosen, Vanessa/ Lathey, Gillian (Hrsg.): Grimms’ Tales around the Globe. The Dynamics of their International Reception (Thomas Bitterlich)
194 Böhm, Kerstin: Archaisierung und Pinkifizierung. Mythen von Weiblichkeit und Männlichkeit in der Kinder- und Jugendliteratur. – Dangendorf, Sarah: Kleine Mädchen in High Heels. Über die visuelle Sexualisierung frühadoleszenter Mädchen (Annette Kliewer)
197 Gordon, Ian: Kid Comic Strips. A Genre Across Four Countries. – Kupczynska, Kalina/Renata Makarska (Hrsg.): Comic in Polen. Polen im Comic. – Kutch, Lynn Marie (Hrsg.): Novel Perspectives on German-Language Comics Studies. History, Pedagogy, Theory. – Reddition. Zeitschrift für Graphische Literatur (66) 2017: Ein halbes Jahrhundert Carlsen Comics. – Rosenfeldt, Reginald: ComicPioniere. Die deutschen Comic-Künstler der 1950er Jahre (Felix Giesa)
The proton drip-line nucleus 17Ne is investigated experimentally in order to determine its two-proton halo character. A fully exclusive measurement of the 17Ne(p, 2p)16F∗ →15O+p quasi-free one-proton knockout reaction has been performed at GSI at around 500 MeV/nucleon beam energy. All particles resulting from the scattering process have been detected. The relevant reconstructed quantities are the angles of the two protons scattered in quasi-elastic kinematics, the decay of 16F into 15O (including γ decays from excited states) and a proton, as well as the 15O+p relative-energy spectrum and the 16F momentum distributions. The latter two quantities allow an independent and consistent determination of the fractions of l = 0 and l = 2 motion of the valence protons in 17Ne. With a resulting relatively small l = 0 component of only around 35(3)%, it is concluded that 17Ne exhibits a rather modest halo character only. The quantitative agreement of the two values deduced from the energy spectrum and the momentum distributions supports the theoretical treatment of the calculation of momentum distributions after quasi-free knockout reactions at high energies by taking into account distortions based on the Glauber theory. Moreover, the experimental data allow the separation of valence-proton knockout and knockout from the 15O core. The latter process contributes with 11.8(3.1) mb around 40% to the total proton-knockout cross section of 30.3(2.3) mb, which explains previously reported contradicting conclusions derived from inclusive cross sections.
New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of data from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. The resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure.
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Objectives: The aim of this multicenter retrospective study was to investigate safety and efficacy of direct acting antiviral (DAA) treatment in the rare subgroup of patients with HCV/HIV-coinfection and advanced liver cirrhosis on the liver transplant waiting list or after liver transplantation, respectively.
Methods: When contacting 54 German liver centers (including all 23 German liver transplant centers), 12 HCV/HIV-coinfected patients on antiretroviral combination therapy were reported having received additional DAA therapy while being on the waiting list for liver transplantation (patient characteristics: Child-Pugh A (n = 6), B (n = 5), C (n = 1); MELD range 7–21; HCC (n = 2); HCV genotype 1a (n = 8), 1b (n = 2), 4 (n = 2)). Furthermore, 2 HCV/HIV-coinfected patients were denoted having received DAA therapy after liver transplantation (characteristics: HCV genotype 1a (n = 1), 4 (n = 1)).
Results: Applied DAA regimens were SOF/DAC (n = 7), SOF/LDV/RBV (n = 3), SOF/RBV (n = 3), PTV/r/OBV/DSV (n = 1), or PTV/r/OBV/DSV/RBV (n = 1), respectively. All patients achieved SVR 12, in the end. In one patient, HCV relapse occurred after 24 weeks of SOF/DAC therapy; subsequent treatment with 12 weeks PTV/r/OBV/DSV achieved SVR 12. One patient underwent liver transplantation while on DAA treatment. Analysis of liver function revealed either stable parameters or even significant improvement during DAA therapy and in follow-up. MELD scores were found to improve in 9/13 therapies in patients on the waiting list for liver transplantation; in only 2 patients a moderate increase of MELD scores persisted at the end of follow-up.
Conclusion: DAA treatment was safe and highly effective in this nation-wide cohort of patients with HCV/HIV-coinfection awaiting liver transplantation or being transplanted.
Background: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.
Methods: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.
Results: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.
Conclusions: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-µm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V–VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I–II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with "acute" (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension.
Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Um zu überprüfen, ob sich die Artenzusammensetzung alpiner Kalk-Magerrasen (Blaugras-Horstseggenrasen, Polsterseggenrasen) im Nationalpark Berchtesgaden während der letzten drei Jahrzehnte geändert hat, wurden Vegetationsaufnahmen aus den 1980er Jahren 2013/14 zum zweiten Mal wiederholt vegetationskundlich erfasst.
Ziel der Arbeit war es, durch den Vergleich der Aufnahmenkollektive Vegetationsveränderungen während der letzten drei Jahrzehnte aufzuzeigen und diese als allogene oder autogene Prozesse zu interpretieren. Dabei wurde insbesondere der Frage nachgegangen, ob anthropogene Stickstoff-Einträge als Hauptursache für mögliche Veränderungen angesehen werden können.
Tatsächlich konnten ausgeprägte floristische Veränderungen im Vergleichszeitraum aufgezeigt werden. So hat sich seit den 1980er Jahre die mittlere Artenzahl sowohl im Polsterseggenrasen als auch im Horstseggenrasen um mehr als 10 Arten pro Aufnahmefläche erhöht. Im Polsterseggenrasen wurde ferner eine signifikante Abnahme der mittleren Kontinentalitätszahlen nachgewiesen.
Die dokumentierten floristischen Veränderungen könnten auf die globale Erwärmung und die damit verbundenen Klimaeffekte zurückzuführen sein. Auch natürlich ablaufende Sukzessionsprozesse könnten die aufgezeigten Änderungen in der Artenzusammensetzung erklären, allerdings ist die Zeitspanne von 30 Jahren zu kurz, als dass eine autogene Sukzession als der Hauptfaktor angesehen werden kann. Denkbar ist aber, dass Sukzessionsprozesse durch die globale Erwärmung heutzutage beschleunigt ablaufen. Stickstoffeinträge oder Landnutzungsänderungen spielen als Erklärungsmodell für die Vegetationsveränderungen dagegen wohl eher eine untergeordnete Rolle.
Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity.
Potentilla heptaphylla gehört in Hessen zu den oft verkannten Arten. Durch Herbarbelege bestätigt sind Vorkommen bei Niederkleen, Münzenberg sowie in Nordhessen um Korbach und Waldeck. Für diese Vorkommen konnte die diploide Chromosomenzahl von 2n = 14 bestätigt werden. Ein Vorkommen im Frankfurter Wald ist erloschen. In Nordhessen wurden außerdem tetraploide Pflanzen festgestellt, bei denen es sich eventuell um Bastarde zwischen Potentilla heptaphylla und P. neumanniana handelt.
Mittels molekulargenetischer Elternschaftsanalyse wurde eine niedrige Rate gemischter Mutterschaften in Bruten der sozial monogamen Tannenmeise nachgewiesen, einer Art, die sich durch hohe Fremdvaterschaftsraten auszeichnet. Gemischte Mutterschaften wurden in vier (= 0,8 %) von 483 Bruten entdeckt und nur für zehn (= 0,3 %) von 3563 erfolgreich genotypisierten Nachkommen wurde die Putativmutter von der genetischen Mutterschaft ausgeschlossen. In Anbetracht dieser sehr niedrigen Rate kann in evolutionsbiologischen Studien der soziale Fortpflanzungserfolg mit dem genetischen Fortpflanzungserfolg für Weibchen der Tannenmeise ohne weiteres gleichgesetzt werden. Die Putativväter wurden ebenfalls in allen Fällen von der genetischen Elternschaft ausgeschlossen, was Quasiparasitismus als Erklärung für gemischte Mutterschaften ausschließt. In einem Fall konnten die Partner eines Brutpaares, das zeitgleich in der Nähe eine eigene Brut aufzog, zweifelsfrei als die genetischen Eltern eines einzelnen Nachkommen identifiziert werden. Mögliche
Ursachen für das Auftreten gemischter Mutterschaften bei der Tannenmeise schließen die Übernahme von
Nistkästen samt begonnenen Gelegen nach dem Tod oder Abwandern der Vorbesitzer und innerartlichen
Brutparasitismus ein.
From 12.12.2010 to 17.12.2010, the Dagstuhl Seminar 10501 "Advances and Applications of Automata on Words and Trees" was held in Schloss Dagstuhl - Leibniz Center for Informatics. During the seminar, several participants presented their current research, and ongoing work and open problems were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available.
Seminar: 10501 - Advances and Applications of Automata on Words and Trees. The aim of the seminar was to discuss and systematize the recent fast progress in automata theory and to identify important directions for future research. For this, the seminar brought together more than 40 researchers from automata theory and related fields of applications. We had 19 talks of 30 minutes and 5 one-hour lectures leaving ample room for discussions. In the following we describe the topics in more detail.
Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na(+)-dependent [(3)H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.
As second part of a series focusing on the Pannonian grasslands of Austria, we present a detailed classification of the grasslands of the Vienna Woods (Wienerwald). This region, although geographically belonging to the Alps, has strong floristic affinities to the Pannonian Basin. The eastern slopes of the Vienna Woods are a hotspot of xero-thermophytic vegetation and exhibit the highest vascular plant species richness in Austria at a scale of 3' x 5'. We used the TWINSPAN classification of a large data set reported in the first part of this series as starting point. Relevés that were considered as misclassified at the level of alliances were manually re-arranged. From this table, an excerpt containing only the relevés of the Vienna Woods was used for the present study (1055 plots). We re-classified the relevés preliminary labelled as Arrhenatherion with another TWINSPAN run. Clusters for which no ecological difference could be detected were merged. The final delimitation of associations and subassociations was achieved by adjusting their diagnostic species so as to get units that were most informative in terms of environmental conditions. All re-arrangements were based on the summarised cover of diagnostic species within individual relevés. As a result, the grasslands of the Vienna Woods are classified within 22 associations (plus two subassociations) belonging to ten alliances and four classes. Within the Seslerio-Festucion pallentis, a new association Scorzonero austriacae-Caricetum humilis is described. The semi-dry grasslands of the study area previously classified as Onobrychido-Brometum are de-scribed as new association Filipendulo vulgaris-Brometum erecti and assigned to the Cirsio-Brachypodion. The Anthoxantho-Agrostietum tenuis is reported for Austria for the first time, and its syntaxonomy is discussed within a broader geographical context.
Herausforderungen für die nationale, regionale und thematische Webarchivierung und deren Nutzung
(2015)
Das World Wide Web ist als weltweites Informations- und Kommunikationsmedium etabliert. Neue Technologien erweitern regelmäßig die Nutzungsformen und erlauben es auch unerfahrenen Nutzern, Inhalte zu publizieren oder an Diskussionen teilzunehmen. Daher wird das Web auch als eine gute Dokumentation der heutigen Gesellschaft angesehen. Aufgrund seiner Dynamik sind die Inhalte des Web vergänglich und neue Technologien und Nutzungsformen stellen regelmäßig neue Herausforderungen an die Sammlung von Webinhalten für die Webarchivierung. Dominierten in den Anfangstagen der Webarchivierung noch statische Seiten, so hat man es heute häufig mit dynamisch generierten Inhalten zu tun, die Informationen aus verschiedenen Quellen integrieren. Neben dem klassischen domainorientieren Webharvesting kann auch ein steigendes Interesse aus verschiedenen Forschungsdisziplinen an thematischen Webkollektionen und deren Nutzung und Exploration beobachtet werden. In diesem Artikel werden einige Herausforderungen und Lösungsansätze für die Sammlung von thematischen und dynamischen Inhalten aus dem Web und den sozialen Medien vorgestellt. Des Weiteren werden aktuelle Probleme der wissenschaftlichen Nutzung diskutiert und gezeigt, wie Webarchive und andere temporale Kollektionen besser durchsucht werden können.
Die Fundmeldungen in Band 33 von Botanik und Naturschutz in Hessen stammen von: Dirk Bönsel, Martin de Jong, Wolfgang Ehmke, Peter Emrich, Benjamin Feller, Brunhilde Göbel, Thomas Gregor, Arthur Händler, Sylvain Hodvina, Gerwin Kasperek, Egbert Korte, Ute Lange, Stefan Meyer, Hasko Friedrich Nesemann, Uwe Raabe, Bernd Sauerwein, Marco Schmidt, Christof Nikolaus Schröder, Antje Schwab, Rainer Stoodt und Michael Uebeler.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.
We apply seismic full waveform inversion to SH‐ and Love‐wave data for investigating the near‐surface lithology at an archaeological site. We evaluate the resolution of the applied full waveform inversion algorithm through ground truthing in the form of an excavation and sediment core studies. Thereby, we investigate the benefits of full waveform inversion in comparison with other established methods of near‐surface prospecting in terms of resolution capabilities and interpretation security. The study is performed in a presumed harbour area of the ancient Thracian city of Ainos. The exemplary target is the source of a linear magnetic anomaly oriented perpendicular to the coast, which was found in a previous magnetic gradiometry survey, suggesting a mole. The SH‐wave full waveform inversion recovered a subsurface SH‐wave velocity model with submeter resolution showing lateral and vertical velocity variation between 40 and 150 m/s. To tame the non‐linearity of the full waveform inversion, a sequential inversion of frequency bands has to be combined with time‐windowing in order to separate the Love wave from the reflected SH wavefield. We compare the full waveform inversion results with multichannel analysis of surface waves, standard seismic reflection imaging, electrical resistivity tomography and electromagnetic induction. It turns out that the respective depth sections are correlated to a certain degree with the full waveform inversion results. However, the structural resolution of the other geophysical methods is significantly lower than for the full waveform inversion. An exception is the reflection seismic imaging, which shows the same resolution as full waveform inversion but can only be interpreted together with the full waveform inversion–based velocity model. An archaeological excavation as well as coring data allows ground truthing and a direct understanding of the geophysical structures. The results show that the target was a sort of near‐surface trench of about 3–4 m width and 0.8 m to 1.0 m depth, filled with silty sediment, which differs from the layered surrounding in colour and composition. The ground truthing revealed that only SH‐wave full waveform inversion and seismic reflection imaging could image the trench and sediment structure with satisfying lateral and depth resolution. We emphasize that the velocity distribution from SH‐wave full waveform inversion agrees closely with the excavated subsurface structures, and that the discovered changes in seismic velocity correlate with changes in the sand content in the respective sediment facies sequences. The study demonstrated that SH‐wave full waveform inversion is capable to image structural and lithological changes in the near subsurface at scales as low as 0.5 m, thus providing the high resolution needed for archaeological and geoarchaeological prospection.
Throughout mankind’s history, the need to secure and protect the home settlement was an essential one. This holds especially true for the city of Ainos (modern Enez) in Turkish Thrace. Due to its continuous settlement history since the 7th/6th century BC, several different types of city walls were built—sometimes even on top of each other—several of which have been preserved over time. To decipher the construction style, the course and the age of a buried city wall segment in the southern part of the former city, a geoscientific multi-proxy approach including magnetic gradiometer (MG) and electrical resistivity tomography (ERT) measurements in combination with granulometrical, sedimentological and microfaunistical investigations on sediment cores was applied. We were able to (1) present reasonable arguments for its Hellenistic age; (2) reveal the course of this wall segment and extrapolate it further north into a less studied area; and (3) demonstrate that in this near-coastal area, the former swampy terrain had been consolidated for constructing the wall. Our multi-proxy approach serves as a valuable example for investigating buried structures in archaeological contexts, avoiding a less-economical, time-consuming, or even forbidden excavation.
This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, all patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.
Purpose: To determine the value of the 2D multiple-echo data image combination (MEDIC) sequence relative to the short-tau inversion recovery (STIR) sequence regarding the depiction of chondral lesions in the patellofemoral joint.
Materials and methods: During a period of 6 month patients with acute pain at the anterior aspect of the knee, joint effusion and suspected chondral lesion defect in the patellofemoral joint underwent MRI including axial MEDIC and STIR imaging. Patients with chondral lesions in the patellofemoral joint on at least one sequence were included. The MEDIC and STIR sequence were quantitatively compared regarding the patella cartilage-to-effusion contrast-to-noise ratio (CNR) and qualitatively regarding the depiction of chondral lesions independently scored by two radiologists on a 3-point scale (1 = not depicted; 2 = blurred depicted; 3 = clearly depicted) using the Wilcoxon-Mann-Whitney-Test. For the analysis of inter-observer agreement the Cohen's Weighted Kappa test was used.
Results: 30 of 58 patients (male: female, 21:9; age: 44 ± 12 yrs) revealed cartilage lesions (fissures, n = 5 including fibrillation; gaps, n = 15; delamination, n = 7; osteoarthritis, n = 3) and were included in this study. The STIR-sequence was significantly (p < 0.001) superior to the MEDIC-sequence regarding both, the patella cartilage-to-effusion CNR (mean CNR: 232 ± 61 vs. 40 ± 16) as well as the depiction of chondral lesion (mean score: 2.83 ± 0.4 vs. 1.75 ± 0.7) with substantial inter-observer agreement in the rating of both sequences (κ = 0.76–0.89).
Conclusion: For the depiction of chondral lesions in the patellofemoral joint, the axial STIR-sequence should be chosen in preference to the axial MEDIC-sequence.
Outcomes of SARS-CoV-2 infections in patients with neurodegenerative diseases in the LEOSS cohort
(2021)
The impact of preexisting neurodegenerative diseases on superimposed SARS-CoV-2 infections remains controversial. Here we examined the course and outcome of SARS-CoV-2 infections in patients affected by Parkinson's disease (PD) or dementia compared to matched controls without neurodegenerative diseases in the LEOSS (Lean European Open Survey on SARS-CoV-2-infected patients) cohort, a large-scale prospective multicenter cohort study...
Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies
(2012)
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.