74 research outputs found

    Properties of the CsI(Tl) detector elements of the CALIFA detector

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    In the R3B experiment at FAIR, charged particles with energies up to 600 MeV and forward boosted Îł-rays with energies up to 20 MeV need to be detected in scattering experiments. Calorimeters for nuclear physics experiments of this kind, using relativistic radioactive ion beams, require high energy resolution and high efficiency for simultaneous detection of strongly Doppler shifted Îł-rays and high-energy charged particles. A calorimeter design that can meet these requirements, using CsI(Tl) scintillators, results in detector elements that may exhibit light output variations with crystal depth, which can limit the attainable resolution. In this paper we present results from a systematic study of 478 detector modules of CALIFA, the R3B calorimeter, in order to determine and minimize such variations. To facilitate further systematic studies we also present results for the total absorption length of the scintillation light, using spectrophotometry, light crosstalk between adjacent detector modules, and surface topography of the CsI(Tl) crystals from atomic force microscopy.Swedish research council | Ref. 2017-03986Swedish research council | Ref. 2014-06644Swedish research council | Ref. 2013-04178Swedish research council | Ref. 2012-04550BMBF, Alemania | Ref. 05P15WOFNABMBF, Alemania | Ref. 05P19WOFN1BMBF, Alemania | Ref. 05P15RDFN1BMBF, Alemania | Ref. 05P19RDFN

    Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

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    Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner

    Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

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    Background Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Methods Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. Results The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. Conclusions For the first time this data associates altered CDK5 substrate phosphorylation with oncogenesis in some but not all tumour types, implicating altered CDK5 activity in aspects of pathogenesis. These data identify a novel oncogenic mechanism where CDK5 activation induces CRMP2A phosphorylation in the nuclei of tumour cells

    Invasive cells in animals and plants: searching for LECA machineries in later eukaryotic life

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    Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study.

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    International audiencePURPOSE: To characterize response shift effects in patients with breast cancer (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions. RESULTS: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC
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