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Neutron-induced reaction cross sections are important for a wide variety of research fields ranging from the study of nuclear level densities, nucleosynthesis to applications of nuclear technology like design, and criticality and safety assessment of existing and future nuclear reactors, radiation dosimetry, medical applications, nuclear waste transmutation, accelerator-driven systems and fuel cycle investigations. Simulations and calculations of nuclear technology applications largely rely on evaluated nuclear data libraries. The evaluations in these libraries are based both on experimental data and theoretical models. CERN’s neutron time-of-flight facility n_TOF has produced a considerable amount of experimental data since it has become fully operational with the start of its scientific measurement programme in 2001. While for a long period a single measurement station (EAR1) located at 185 m from the neutron production target was available, the construction of a second beam line at 20 m (EAR2) in 2014 has substantially increased the measurement capabilities of the facility. An outline of the experimental nuclear data activities at n_TOF will be presented.
New results are presented of the 234U neutron-induced fission cross section, obtained with high accuracy in the resonance region by means of two methods using the 235U(n,f) as reference. The recent evaluation of the 235U(n,f) obtained with SAMMY by L. C. Leal et al. (these Proceedings), based on previous n_TOF data [1], has been used to calculate the 234U(n,f) cross section through the 234U/235U ratio, being here compared with the results obtained by using the n_TOF neutron flux.
High precision measurement of the radiative capture cross section of 238U at the n_TOF CERN facility
(2017)
The importance of improving the accuracy on the capture cross-section of 238U has been addressed by the Nuclear Energy Agency, since its uncertainty significantly affects the uncertainties of key design parameters for both fast and thermal nuclear reactors. Within the 7th framework programme ANDES of the European Commission three different measurements have been carried out with the aim of providing the 238U(n,γ) cross-section with an accuracy which varies from 1 to 5%, depending on the energy range. Hereby the final results of the measurement performed at the n_TOF CERN facility in a wide energy range from 1 eV to 700 keV will be presented.
Neutron-induced fission cross sections of 238U and 235U are used as standards in the fast neutron region up to 200 MeV. A high accuracy of the standards is relevant to experimentally determine other neutron reaction cross sections. Therefore, the detection effciency should be corrected by using the angular distribution of the fission fragments (FFAD), which are barely known above 20 MeV. In addition, the angular distribution of the fragments produced in the fission of highly excited and deformed nuclei is an important observable to investigate the nuclear fission process.
In order to measure the FFAD of neutron-induced reactions, a fission detection setup based on parallel-plate avalanche counters (PPACs) has been developed and successfully used at the CERN-n_TOF facility. In this work, we present the preliminary results on the analysis of new 235U(n,f) and 238U(n,f) data in the extended energy range up to 200 MeV compared to the existing experimental data.
The elliptic-flow ratio of neutrons with respect to protons or light complex particles in reactions of heavy ions at pre-relativistic energies has been proposed as an observable sensitive to the strength of the symmetry term of the nuclear equation of state at supra-saturation densities. In the ASY-EOS experiment at the GSI laboratory, flows of neutrons and light charged particles were measured for 197Au+197Au collisions at 400 MeV/nucleon. Flow results obtained for the Au+Au system, in comparison with predictions of the UrQMD transport model, confirm the moderately soft to linear density dependence of the symmetry energy deduced from the earlier FOPI-LAND data.
Schriftenschau
(2012)
Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample.
Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates.
Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients.
Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin.
Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.
Hepatitis C virus (HCV) naturally infects only humans and chimpanzees. The determinants responsible for this narrow species tropism are not well defined. Virus cell entry involves human scavenger receptor class B type I (SR-BI), CD81, claudin-1 and occludin. Among these, at least CD81 and occludin are utilized in a highly species-specific fashion, thus contributing to the narrow host range of HCV. We adapted HCV to mouse CD81 and identified three envelope glycoprotein mutations which together enhance infection of cells with mouse or other rodent receptors approximately 100-fold. These mutations enhanced interaction with human CD81 and increased exposure of the binding site for CD81 on the surface of virus particles. These changes were accompanied by augmented susceptibility of adapted HCV to neutralization by E2-specific antibodies indicative of major conformational changes of virus-resident E1/E2-complexes. Neutralization with CD81, SR-BI- and claudin-1-specific antibodies and knock down of occludin expression by siRNAs indicate that the adapted virus remains dependent on these host factors but apparently utilizes CD81, SR-BI and occludin with increased efficiency. Importantly, adapted E1/E2 complexes mediate HCV cell entry into mouse cells in the absence of human entry factors. These results further our knowledge of HCV receptor interactions and indicate that three glycoprotein mutations are sufficient to overcome the species-specific restriction of HCV cell entry into mouse cells. Moreover, these findings should contribute to the development of an immunocompetent small animal model fully permissive to HCV.
Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C.
Methods: Baseline oxLDL was determined in 379 participants with chronic HCV genotype 1 infection from the INDIV-2 study using a commercial enzyme-linked immunosorbent assay. The mechanistic in vitro studies used full-length and subgenomic HCV genomes replicating in hepatoma cells.
Results: In the multivariate analysis, oxLDL was found to be an independent predictor of SVR. Oxidized LDL did not correlate with markers of inflammation (alanine transaminase, ferritin), nor was serum oxLDL affected by exogenous interferon administration. Also, oxLDL did not alter the sensitivity of HCV replication to interferon. However, oxLDL was found to be a potent inhibitor of cell-to-cell spread of HCV between adjacent cells in vitro. It could thus reduce the rate at which new cells are infected by HCV through either the cell-free or cell-to-cell route. Finally, serum oxLDL was significantly associated with the estimated infected cell loss rate under treatment.
Conclusions: Oxidized LDL is a novel predictor of SVR after interferon-based therapy and may explain the previously observed association of LDL with SVR. Rather than being a marker of activated antiviral defenses it may improve chances of SVR by limiting spread of infection to naive cells through the cell-to-cell route.
Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date.
Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer.
Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients.
Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation.
Purpose: Advanced Ewing sarcomas have poor prognosis. They are defined by early relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.
Design: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992 consisted of induction chemotherapy, whole body imaging directed radiotherapy to the primary tumor and metastases, tandem high-dose chemotherapy and autologous rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy to the primary tumor only followed by consolidation chemotherapy.
Results: In MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992 (p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992. Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After exclusion of patients succumbing to treatment related complications (n=3), 7/10 patients survived without BM involvement, in contrast to 0/5 patients with BM involvement. This was confirmed in a multivariate analysis. There was no correlation between BM involvement and the number of metastases at diagnosis.
Conclusion: The MetaEICESS protocols yield long-term disease-free survival in patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was not associated with increased death of complications. Bone marrow involvement is a risk factor distinct from multiple bone metastases.
Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia
(2020)
Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.
Global distributions of profiles of sulphur hexafluoride (SF6) have been retrieved from limb emission spectra recorded by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on Envisat covering the period September 2002 to March 2004. Individual SF6 profiles have a precision of 0.5 pptv below 25 km altitude and a vertical resolution of 4–6 km up to 35 km altitude. These data have been validated versus in situ observations obtained during balloon flights of a cryogenic whole-air sampler. For the tropical troposphere a trend of 0.230±0.008 pptv/yr has been derived from the MIPAS data, which is in excellent agreement with the trend from ground-based flask and in situ measurements from the National Oceanic and Atmospheric Administration Earth System Research Laboratory, Global Monitoring Division. For the data set currently available, based on at least three days of data per month, monthly 5° latitude mean values have a 1 o standard error of 1%. From the global SF6 distributions, global daily and monthly distributions of the apparent mean age of air are inferred by application of the tropical tropospheric trend derived from MIPAS data. The inferred mean ages are provided for the full globe up to 90° N/S, and have a 1 o standard error of 0.25 yr. They range between 0 (near the tropical tropopause) and 7 years (except for situations of mesospheric intrusions) and agree well with earlier observations. The seasonal variation of the mean age of stratospheric air indicates episodes of severe intrusion of mesospheric air during each Northern and Southern polar winter observed, long-lasting remnants of old, subsided polar winter air over the spring and summer poles, and a rather short period of mixing with midlatitude air and/or upward transport during fall in October/November (NH) and April/May (SH), respectively, with small latitudinal gradients, immediately before the new polar vortex starts to form. The mean age distributions further confirm that SF6 is destroyed in the mesosphere to a considerable degree. Model calculations with the Karlsruhe simulation model of the middle atmosphere (KASIMA) chemical transport model agree well with observed global distributions of the mean age only if the SF6 sink reactions in the mesosphere are included in the model.
Transcription factors can serve as links between tumor microenvironment signaling and oncogenesis. Interferon regulatory factor 9 (IRF9) is recruited and expressed upon interferon stimulation and is dependent on cofactors that exert in tumor-suppressing or oncogenic functions via the JAK-STAT pathway. IRF9 is frequently overexpressed in human lung cancer and is associated with decreased patient survival; however, the underlying mechanisms remain to be elucidated. Here, we used stably transduced lung adenocarcinoma cell lines (A549 and A427) to overexpress or knockdown IRF9. Overexpression led to increased oncogenic behavior in vitro, including enhanced proliferation and migration, whereas knockdown reduced these effects. These findings were confirmed in vivo using lung tumor xenografts in nude mice, and effects on both tumor growth and tumor mass were observed. Using RNA sequencing, we identified versican (VCAN) as a novel downstream target of IRF9. Indeed, IRF9 and VCAN expression levels were found to be correlated. We showed for the first time that IRF9 binds at a newly identified response element in the promoter region of VCAN to regulate its transcription. Using an siRNA approach, VCAN was found to enable the oncogenic properties (proliferation and migration) of IRF9 transduced cells, perhaps with CDKN1A involvement. The targeted inhibition of IRF9 in lung cancer could therefore be used as a new treatment option without multimodal interference in microenvironment JAK-STAT signaling.
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.
Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for the cohort without IT and .69 ± .10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without IT: 3-year CIR, .21 ± .05, 3-year CITRM, .10 ± .04; IT patients: 3-year CIR, .18 ± .09, 3-year CITRM .13 ± .07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
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)
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin group from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have dual functionality switching between inward transmembrane proton translocation and photosensory activity, both of which can be modulated with UV light. CryoR1 exhibits two subpopulations in the ground state, which upon light activation lead to transient photocurrents of opposing polarities. A distinguishing feature of the group is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by lit, we demonstrate that the arginine stabilizes a UV-absorbing intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified group and demonstrate principles of the adaptation of these rhodopsins to low temperatures.Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin group from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have dual functionality switching between inward transmembrane proton translocation and photosensory activity, both of which can be modulated with UV light. CryoR1 exhibits two subpopulations in the ground state, which upon light activation lead to transient photocurrents of opposing polarities. A distinguishing feature of the group is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by light, we demonstrate that the arginine stabilizes a UV-absorbing intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified group and demonstrate principles of the adaptation of these rhodopsins to low temperatures.
Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.
Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).
Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.
Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.
Trial registry: ClinicalTrials.gov identifier: NCT03426657.
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.
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
Microbial rhodopsins are omnipresent on Earth, however the vast majority of them remain uncharacterized. Here we describe a new rhodopsin clade from cold-adapted organisms and cold environments, such as glaciers, denoted as CryoRhodopsins (CryoRs). Our data suggest that CryoRs have photosensory activity. A distinguishing feature of the clade is the presence of a buried arginine residue close to the cytoplasmic face of its members. Combining single-particle cryo-electron microscopy and X-ray crystallography with the rhodopsin activation by light, we demonstrate that the arginine stabilizes a strongly blue-shifted intermediate of an extremely slow CryoRhodopsin photocycle. Together with extensive spectroscopic characterization, our investigations on CryoR1 and CryoR2 proteins reveal mechanisms of photoswitching in the newly identified clade and demonstrate principles of the adaptation of these rhodopsins to low temperatures.
Establishing and maintaining protected areas (PAs) is a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting PAs based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences as well as real-time comparison of the outcome. Applying the tool across 1,346 terrestrial PAs, we demonstrate that decision makers frequently face trade-offs among conflicting objectives, e.g., between species protection and ecosystem integrity. Nevertheless, we show that transparent decision support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.
Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (~ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection.
Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L).
Results: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05).
Conclusion: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
The establishment and maintenance of protected areas(PAs) is viewed as a key action in delivering post-2020 biodiversity targets. PAs often need to meet a multitude of objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation. As available land and conservation funding are limited, optimizing resources by selecting the most beneficial PAs is vital. Here we present a decision support tool that enables a flexible approach to PA selection on a global scale, allowing different conservation objectives to be weighted and prioritized according to user-specified preferences. We apply the tool across 1347 terrestrial PAs and highlight frequent trade-offs among different objectives, e.g., between biodiversity protection and ecosystem integrity. These results indicate that decision makers must usually decide among conflicting objectives. To assist this our decision support tool provides an explicitly value-based approach that can help resolve such conflicts by considering divergent societal and political demands and values.
The establishment and maintenance of protected areas (PAs) is viewed as a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting protected areas based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences, as well as real-time comparison of the selected areas that result from such different priorities. We apply the tool across 1347 terrestrial PAs and highlight frequent trade-offs among different objectives, e.g., between species protection and ecosystem integrity. Outputs indicate that decision makers frequently face trade-offs among conflicting objectives. Nevertheless, we show that transparent decision-support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.
LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.
The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the spin-orbit shell gap towards the neutron dripline. To do so, we employed (p,2p) quasi-free scattering reactions to measure the proton component of the state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton spin-orbit splitting, at variance to recent claims for a prevalent magic number towards the neutron dripline.
The quasi-free scattering reactions 11C(p, 2p) and 10,11,12C(p, pn) have been studied in inverse kinematics at beam energies of 300–400 MeV/u at the R3B-LAND setup. The outgoing proton-proton and protonneutron pairs were detected in coincidence with the reaction fragments in kinematically complete measurements. The efficiency to detect these pairs has been obtained from GEANT4 simulations which were tested using the 12C(p, 2p) and 12C(p, pn) reactions. Experimental cross sections and momentum distributions have been obtained and compared to DWIA calculations based on eikonal theory. The new results reported here are combined with previously published cross sections for quasi-free scattering from oxygen and nitrogen isotopes and together they enable a systematic study of the reduction of singleparticle strength compared to predictions of the shell model over a wide neutron-to-proton asymmetry range. The combined reduction factors show a weak or no dependence on isospin asymmetry, in contrast to the strong dependency reported in nucleon-removal reactions induced by nuclear targets at lower energies. However, the reduction factors for (p, 2p) are found to be ’significantly smaller than for (p, pn) reactions for all investigated nuclei.
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.
DNA methylation is a major regulatory process of gene transcription, and aberrant DNA methylation is associated with various diseases including cancer. Many compounds have been reported to modify DNA methylation states. Despite increasing interest in the clinical application of drugs with epigenetic effects, and the use of diagnostic markers for genome-wide hypomethylation in cancer, large-scale screening systems to measure the effects of drugs on DNA methylation are limited. In this study, we improved the previously established fluorescence polarization-based global DNA methylation assay so that it is more suitable for application to human genomic DNA. Our methyl-sensitive fluorescence polarization (MSFP) assay was highly repeatable (inter-assay coefficient of variation = 1.5%) and accurate (r2 = 0.99). According to signal linearity, only 50–80 ng human genomic DNA per reaction was necessary for the 384-well format. MSFP is a simple, rapid approach as all biochemical reactions and final detection can be performed in one well in a 384-well plate without purification steps in less than 3.5 hours. Furthermore, we demonstrated a significant correlation between MSFP and the LINE-1 pyrosequencing assay, a widely used global DNA methylation assay. MSFP can be applied for the pre-screening of compounds that influence global DNA methylation states and also for the diagnosis of certain types of cancer.
New results from the energy scan programme of NA49, in particular kaon production at 30 AGeV and phi production at 40 and 80 AGeV are presented. The K+/pi+ ratio shows a pronounced maximum at 30 AGeV; the kaon slope parameters are constant at SPS energies. Both findings support the scenario of a phase transition at about 30 AGeV beam energy. The phi/pi ratio increases smoothly with beam energy, showing an energy dependence similar to K-/pi-. The measured particle yields can be reproduced by a hadron gas model, with chemical freeze-out parameters on a smooth curve in the T-muB plane. The transverse spectra can be understood as resulting from a rapidly expanding, locally equilibrated source. No evidence for an earlier kinetic decoupling of heavy hyperons is found.
Directed and elliptic flow of charged pions and protons in Pb + Pb collisions at 40 and 158 A GeV
(2003)
Directed and elliptic flow measurements for charged pions and protons are reported as a function of transverse momentum, rapidity, and centrality for 40 and 158A GeV Pb + Pb collisions as recorded by the NA49 detector. Both the standard method of correlating particles with an event plane, and the cumulant method of studying multiparticle correlations are used. In the standard method the directed flow is corrected for conservation of momentum. In the cumulant method elliptic flow is reconstructed from genuine 4, 6, and 8-particle correlations, showing the first unequivocal evidence for collective motion in A+A collisions at SPS energies.
Background: Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly.
Methods: A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus.
Results: CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis.
Conclusions: CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome.
To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.
Im Rahmen der Kartierung der Gefäßpflanzenflora des Vor-, Hochund kammnahen Hintertaunus wurde im Jahre 2004 ein großer Bestand des für Deutschland bislang selten erwähnten Doronicum ×willdenowii entdeckt. Da sich die Art bis heute nicht nur gehalten, sondern vermehrt hat, besteht offensichtlich ein Trend zur lokalen Einbürgerung.
In this paper, we present an experimental and theoretical study of excitation processes for the heaviest stable helium-like ion, that is, He-like uranium occurring in relativistic collisions with hydrogen and argon targets. In particular, we concentrate on angular distributions of the characteristic Kα radiation following the K → L excitation of He-like uranium. We pay special attention to the magnetic sub-level population of the excited 1s2lj states, which is directly related to the angular distribution of the characteristic Kα radiation. We show that the experimental data can be well described by calculations taking into account the excitation by the target nucleus as well as by the target electrons. Moreover, we demonstrate for the first time an important influence of the electron-impact excitation process on the angular distributions of the Kα radiation produced by excitation of He-like uranium in collisions with different targets.
Bei den im Rahmen des Forschungsverbundes erfolgten faunistischen Untersuchungen stand die Charakterisierung der unterschiedlichen, vor allem aber der wertvollen Biotoptypen der Braunkohlenfolgelandschaft mit Hilfe der dort lebenden Tierarten bzw. Artengemeinschaften im Vordergrund. Es wurden Tiergruppen bearbeitet, die zum einen ein hohes indikatorisches Potential besitzen, zum anderen unterschiedliche ökologische Hierachieebenen repräsentieren. Eine Auswertung der Ergebnisse erfolgte zumeist auf der Ebene der Biotoptypengruppen (siehe Heyde; Jakob; Köck; Reuter im gleichen Heft).
Immunosuppressive compounds affect the fungal growth and viability of defined aspergillus species
(2019)
Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.