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Psoriasis is a frequent and often severe inflammatory skin disease, characterized by altered epidermal homeostasis. Since we found previously that Akt/mTOR signaling is hyperactivated in psoriatic skin, we aimed at elucidating the role of aberrant mTORC1 signaling in this disease. We found that under healthy conditions mTOR signaling was shut off when keratinocytes switch from proliferation to terminal differentiation. Inflammatory cytokines (IL-1β, IL-17A, TNF-α) induced aberrant mTOR activity which led to enhanced proliferation and reduced expression of differentiation markers. Conversely, regular differentiation could be restored if mTORC1 signaling was blocked. In mice, activation of mTOR through the agonist MHY1485 also led to aberrant epidermal organization and involucrin distribution. In summary, these results not only identify mTORC1 as an important signal integrator pivotal for the cells fate to either proliferate or differentiate, but emphasize the role of inflammation-dependent mTOR activation as a psoriatic pathomechanism.
Background: Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies.
Methods: Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied.
Results: Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0–4) as well as 2.3 per biopsy (0–6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen.
Conclusion: Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation.
Translational impact: The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.
PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells
(2011)
PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.
The correspondence between the terminology used for querying and the one used in content objects to be retrieved, is a crucial prerequisite for effective retrieval technology. However, as terminology is evolving over time, a growing gap opens up between older documents in (long-term) archives and the active language used for querying such archives. Thus, technologies for detecting and systematically handling terminology evolution are required to ensure "semantic" accessibility of (Web) archive content on the long run. As a starting point for dealing with terminology evolution this paper formalizes the problem and discusses issues, first ideas and relevant technologies.
The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.
Recombinase-mediated cassette exchange (RMCE) exploits the possibility to unidirectionally exchange any genetic material flanked by heterotypic recombinase recognition sites (RRS) with target sites in the genome. Due to a limited number of available pre-fabricated target sites, RMCE in mouse embryonic stem (ES) cells has not been tapped to its full potential to date. Here, we introduce a universal system, which allows the targeted insertion of any given transcriptional unit into 85 742 previously annotated retroviral conditional gene trap insertions, representing 7013 independent genes in mouse ES cells, by RMCE. This system can be used to express any given cDNA under the control of endogenous trapped promoters in vivo, as well as for the generation of transposon ‘launch pads’ for chromosomal region-specific ‘Sleeping Beauty’ insertional mutagenesis. Moreover, transcription of the gene-of-interest is only activated upon Cre-recombinase activity, a feature that adds conditionality to this expression system, which is demonstrated in vivo. The use of the RMCE system presented in this work requires one single-cloning step followed by one overnight gateway clonase reaction and subsequent cassette exchange in ES cells with efficiencies of 40% in average.
Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as the second leading cause of cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in the development and progression of different types of human cancers. However, the mechanism and role of TGM2 in colorectal cancer are poorly understood. Here, we present TGM2 as a promising drug target.
In primary patient material of CRC patients, we detected an increased expression and enzymatic activity of TGM2 in colon cancer tissue in comparison to matched normal colon mucosa cells. The genetic ablation of TGM2 in CRC cell lines using shRNAs or CRISPR/Cas9 inhibited cell expansion and tumorsphere formation. In vivo, tumor initiation and growth were reduced upon genetic knockdown of TGM2 in xenotransplantations. TGM2 ablation led to the induction of Caspase-3-driven apoptosis in CRC cells. Functional rescue experiments with TGM2 variants revealed that the transamidation activity is critical for the pro-survival function of TGM2. Transcriptomic and protein–protein interaction analyses applying various methods including super-resolution and time-lapse microscopy showed that TGM2 directly binds to the tumor suppressor p53, leading to its inactivation and escape of apoptosis induction.
We demonstrate here that TGM2 is an essential survival factor in CRC, highlighting the therapeutic potential of TGM2 inhibitors in CRC patients with high TGM2 expression. The inactivation of p53 by TGM2 binding indicates a general anti-apoptotic function, which may be relevant in cancers beyond CRC.
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.
Chordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (n = 11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.7% of samples and co-occurred with genomic instability. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, which is preferentially toxic to HR-incompetent cells, led to prolonged clinical benefit in a patient with refractory chordoma, and whole-genome analysis at progression revealed a PARP1 p.T910A mutation predicted to disrupt the autoinhibitory PARP1 helical domain. These findings uncover a therapeutic opportunity in chordoma that warrants further exploration, and provide insight into the mechanisms underlying PARP inhibitor resistance.
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.
In contrast to the commonly indolent clinical behavior of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), T cell/histiocyte rich large B cell lymphoma (THRLBCL) is frequently diagnosed in advanced clinical stages and has a poor prognosis. Besides the different clinical presentations of these lymphoma entities, there are variants of NLPHL with considerable histopathologic overlap compared to THRLBCL. Especially THRLBCL-like NLPHL, a diffuse form of NLPHL, often presents a histopathologic pattern similar to THRLBCL, suggesting a close relationship between both lymphoma entities. To corroborate this hypothesis, we performed gene expression profiling of microdissected tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. In unsupervised analyses, the lymphomas did not cluster according to their entity. Moreover, even in supervised analyses, very few consistently differentially expressed transcripts were found, and for these genes the extent of differential expression was only moderate. Hence, there are no clear and consistent differences in the gene expression of the tumor cells of NLPHL, THRLBCL-like NLPHL and THRLBCL. Based on the gene expression studies, we identified BAT3/BAG6, HIGD1A, and FAT10/UBD as immunohistochemical markers expressed in the tumor cells of all three lymphomas. Characterization of the tumor microenvironment for infiltrating T cells and histiocytes revealed significant differences in the cellular composition between typical NLPHL and THRLBCL cases. However, THRLBCL-like NLPHL presented a histopathologic pattern more related to THRLBCL than NLPHL. In conclusion, NLPHL and THRLBCL may represent a spectrum of the same disease. The different clinical behavior of these lymphomas may be strongly influenced by differences in the lymphoma microenvironment, possibly related to the immune status of the patient at the timepoint of diagnosis.
The electron-capture process was studied for Xe54+ colliding with H2 molecules at the internal gas target of the Experimental Storage Ring (ESR) at GSI, Darmstadt. Cross-section values for electron capture into excited projectile states were deduced from the observed emission cross section of Lyman radiation, being emitted by the hydrogenlike ions subsequent to the capture of a target electron. The ion beam energy range was varied between 5.5 and 30.9 MeV/u by applying the deceleration mode of the ESR. Thus, electron-capture data were recorded at the intermediate and, in particular, the low-collision-energy regime, well below the beam energy necessary to produce bare xenon ions. The obtained data are found to be in reasonable qualitative agreement with theoretical approaches, while a commonly applied empirical formula significantly overestimates the experimental findings.
The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.
The experimental area 2 (EAR-2) at CERNs neutron time-of-flight facility (n_TOF), which is operational since 2014, is designed and built as a short-distance complement to the experimental area 1 (EAR-1). The Parallel Plate Avalanche Counter (PPAC) monitor experiment was performed to characterize the beam pro↓le and the shape of the neutron 'ux at EAR-2. The prompt γ-flash which is used for calibrating the time-of-flight at EAR-1 is not seen by PPAC at EAR-2, shedding light on the physical origin of this γ-flash.
We report the first measurement of low-energy proton-capture cross sections of 124Xe in a heavy-ion storage ring. 124Xe54+ ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The 125Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.
The 124Xe(p,γ) reaction has been measured for the first time at energies around the Gamow window by using stored ions at the ESR facility. The desired beam energies below 10 MeV/u introduce new experimental challenges like windowless ions detection under UHV conditions, extremely short beam lifetimes and efficient beam deceleration and cooling, all of which have been successfully met.
Hintergrund: Ab Frühjahr 2020 kam es zur weltweiten Verbreitung von SARS-CoV‑2 mit der heute als erste Welle der Pandemie bezeichneten Phase ab März 2020. Diese resultierte an vielen Kliniken in Umstrukturierungen und Ressourcenverschiebungen. Ziel unserer Arbeit war die Erfassung der Auswirkungen der Pandemie auf die universitäre Hals-Nasen-Ohren(HNO)-Heilkunde für die Forschung, Lehre und Weiterbildung. Material und Methoden: Die Direktorinnen und Direktoren der 39 Universitäts-HNO-Kliniken in Deutschland wurden mithilfe einer strukturierten Online-Befragung zu den Auswirkungen der Pandemie im Zeitraum von März bis April 2020 auf die Forschung, Lehre und die Weiterbildung befragt. Ergebnisse: Alle 39 Direktorinnen und Direktoren beteiligten sich an der Umfrage. Hiervon gaben 74,4 % (29/39) an, dass es zu einer Verschlechterung ihrer Forschungstätigkeit infolge der Pandemie gekommen sei. Von 61,5 % (24/39) wurde berichtet, dass pandemiebezogene Forschungsaspekte aufgegriffen wurden. Von allen Kliniken wurde eine Einschränkung der Präsenzlehre berichtet und 97,5 % (38/39) führten neue digitale Lehrformate ein. Im Beobachtungszeitraum sahen 74,4 % der Klinikdirektoren die Weiterbildung der Assistenten nicht gefährdet. Schlussfolgerung: Die Ergebnisse geben einen Einblick in die heterogenen Auswirkungen der Pandemie. Die kurzfristige Bearbeitung pandemiebezogener Forschungsthemen und die Einführung innovativer digitaler Konzepte für die studentische Lehre belegt eindrücklich das große innovative Potenzial und die schnelle Reaktionsfähigkeit der HNO-Universitätskliniken, um auch während der Pandemie ihre Aufgaben in der Forschung, Lehre und Weiterbildung bestmöglich zu erfüllen.
Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects.
Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro.
Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05).
Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects.
Background: Cytogenetic aberrations such as deletion of chromosome 5q (del(5q)) represent key elements in routine clinical diagnostics of haematological malignancies. Currently established methods such as metaphase cytogenetics, FISH or array-based approaches have limitations due to their dependency on viable cells, high costs or semi-quantitative nature. Importantly, they cannot be used on low abundance DNA. We therefore aimed to establish a robust and quantitative technique that overcomes these shortcomings.
Methods: For precise determination of del(5q) cell fractions, we developed an inexpensive multiplex-PCR assay requiring only nanograms of DNA that simultaneously measures allelic imbalances of 12 independent short tandem repeat markers.
Results: Application of this method to n=1142 samples from n=260 individuals revealed strong intermarker concordance (R²=0.77–0.97) and reproducibility (mean SD: 1.7%). Notably, the assay showed accurate quantification via standard curve assessment (R²>0.99) and high concordance with paired FISH measurements (R²=0.92) even with subnanogram amounts of DNA. Moreover, cytogenetic response was reliably confirmed in del(5q) patients with myelodysplastic syndromes treated with lenalidomide. While the assay demonstrated good diagnostic accuracy in receiver operating characteristic analysis (area under the curve: 0.97), we further observed robust correlation between bone marrow and peripheral blood samples (R²=0.79), suggesting its potential suitability for less-invasive clonal monitoring.
Conclusions: In conclusion, we present an adaptable tool for quantification of chromosomal aberrations, particularly in problematic samples, which should be easily applicable to further tumour entities.
A subgroup of pediatric acute T-lymphoblastic leukemia (T-ALL) was characterized by a gene expression profile comparable to that of early T-cell precursors (ETPs) with a highly unfavorable outcome. We have investigated clinical and molecular characteristics of the ETP-ALL subgroup in adult T-ALL. As ETP-ALL represents a subgroup of early T-ALL we particularly focused on this cohort and identified 178 adult patients enrolled in the German Acute Lymphoblastic Leukemia Multicenter studies (05/93–07/03). Of these, 32% (57/178) were classified as ETP-ALL based on their characteristic immunophenotype. The outcome of adults with ETP-ALL was poor with an overall survival of only 35% at 10 years, comparable to the inferior outcome of early T-ALL with 38%. The molecular characterization of adult ETP-ALL revealed distinct alterations with overexpression of stem cell-related genes (BAALC, IGFBP7, MN1, WT1). Interestingly, we found a low rate of NOTCH1 mutations and no FBXW7 mutations in adult ETP-ALL. In contrast, FLT3 mutations, rare in the overall cohort of T-ALL, were very frequent and nearly exclusively found in ETP-ALL characterized by a specific immunophenotype. These molecular characteristics provide biologic insights and implications with respect to innovative treatment strategies (for example, tyrosine kinase inhibitors) for this high-risk subgroup of adult ETP-ALL.
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.
Zielsetzung: Ziel des Projekts ist es, ein longitudinales Modell-Curriculum "Kommunikative und soziale Kompetenzen" für die medizinische Ausbildung zur Diskussion zu stellen. Vorgehen und Ergebnisse: Auf einem 2-tägigen Workshop wurde interfakultär und interdisziplinär auf der Grundlage des "Basler Consensus Statements: Kommunikative und soziale Kompetenzen im Medizinstudium" ein Curriculum entwickelt, das deutschsprachigen Fakultäten bei der Planung und Implementierung als Vorlage dienen kann. Das Modell lässt sich als Gesamt-Curriculum oder in Teilmodulen implementieren. Es kann auch bei der Umstellung auf Bachelor- und Masterstudiengänge genutzt werden. Das longitudinale Modell-Curriculum weist neben 131 definierten Ausbildungszielen geeignete didaktische Konzepte und Prüfungsformate auf und gibt Vorschläge, zu welchem Zeitpunkt die verschiedenen Fächer die entsprechenden Lernziele vermitteln können. Fazit: Mit diesem longitudinalen "Modell-Curriculum Kommunikative und Soziale Kompetenzen" liegt für den deutschen Sprachraum erstmalig ein curriculares Instrument vor, das breite Anwendung an einer Vielzahl deutscher, österreichischer und schweizerischer Fakultäten finden und eine Umsetzung des Bologna-Prozesses auch fakultätsübergreifend vereinfachen kann. Schlüsselwörter: Modell-Curriculum, kommunikative/soziale Kompetenzen, Basler Consensus Statement, medizinische Ausbildung, Didaktik, Prüfung, Bologna-Prozess
The Cosmological Lithium Problem refers to the large discrepancy between the abundance of primordial 7Li predicted by the standard theory of Big Bang Nucleosynthesis and the value inferred from the so-called “Spite plateau” in halo stars. A possible explanation for this longstanding puzzle in Nuclear Astrophysics is related to the incorrect estimation of the destruction rate of 7Be, which is responsible for the production of 95% of primordial Lithium. While charged-particle induced reactions have mostly been ruled out, data on the 7Be(n,α) and 7Be(n,p) reactions are scarce or completely missing, so that a large uncertainty still affects the abundance of 7Li predicted by the standard theory of Big Bang Nucleosynthesis. Both reactions have been measured at the n_TOF facility at CERN, providing for the first time data in a wide neutron energy range.
The 33S(n,α)30Si cross section measurement, using 10B(n,α) as reference, at the n_TOF Experimental Area 2 (EAR2) facility at CERN is presented. Data from 0.01 eV to 100 keV are provided and, for the first time, the cross section is measured in the range from 0.01 eV to 10 keV. These data may be used for a future evaluation of the cross section because present evaluations exhibit large discrepancies. The 33S(n,α)30Si reaction is of interest in medical physics because of its possible use as a cooperative target to boron in Neutron Capture Therapy (NCT).
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.
he study of the resonant structures in neutron-nucleus cross-sections, and therefore of the compound-nucleus reaction mechanism, requires spectroscopic measurements to determine with high accuracy the energy of the neutron interacting with the material under study.
To this purpose, the neutron time-of-flight facility n_TOF has been operating since 2001 at CERN. Its characteristics, such as the high intensity instantaneous neutron flux, the wide energy range from thermal to few GeV, and the very good energy resolution, are perfectly suited to perform high-quality measurements of neutron-induced reaction cross sections. The precise and accurate knowledge of these cross sections plays a fundamental role in nuclear technologies, nuclear astrophysics and nuclear physics.
Two different measuring stations are available at the n_TOF facility, called EAR1 and EAR2, with different characteristics of intensity of the neutron flux and energy resolution. These experimental areas, combined with advanced detection systems lead to a great flexibility in performing challenging measurement of high precision and accuracy, and allow the investigation isotopes with very low cross sections, or available only in small quantities, or with very high specific activity.
The characteristics and performances of the two experimental areas of the n_TOF facility will be presented, together with the most important measurements performed to date and their physics case. In addition, the significant upcoming measurements will be introduced.