Full-length TrkB variant in NSCLC is associated with brain metastasis

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their expression was related to preferential tumor entry into the central nervous system (CNS). By immunohistochemistry, 80% of the ADKs that metastasize to central nervous system expressed TrkB receptor compared to 33% expressing of ADKs without CNS metastasis. Moreover, ADKs with CNS metastasis showed an elevated expression of the full-length TrkB receptor. The TrkB receptor FL/T1 ratio was statistically higher in primary ADKs with brain metastasis compared to ADKs without brain metastasis. Our data indicate that TrkB full-length isoform expression in primary ADK cells may be associated with higher risk to develop brain metastasis. Therefore, TrkB receptor may possess prognostic and therapeutic implications in lung ADK

Inspired or foolhardy: sensemaking, confidence and entrepreneurs' decision-making.

The purpose of this paper is to investigate the role of confidence in how both new and experienced entrepreneurs interpret and make sense of their business environment to inform decision-making. We illustrate our conceptual arguments with descriptive results from a large-scale (n = 6289) survey on entrepreneurs' perception of business performance and their decisions taken at a time of uncertainty in an economic downturn. Quantitative findings are stratified along experiential lines to explore heterogeneity in entrepreneurial decision-making and directly inform our conceptual arguments, while qualitative data from open questions are used to explain the role of confidence. Newer entrepreneurs are found to be more optimistic in the face of environmental risk, which impacts on their decision-making and innovative capabilities. However, the more experienced entrepreneurs warily maintain margin and restructure to adapt to environmental changes. Instead of looking directly at the confidence of individuals, we show how confidence impacts sensemaking, and ultimately, decision-making. These insights inform research on the behaviour of novice and experienced entrepreneurs in relation to innovative business activities. Specifically, blanket assumptions on the role of confidence may be misplaced as its impact changes with experience to alter how entrepreneurs make sense of their environment

Measurement of global polarization of {\Lambda} hyperons in few-GeV heavy-ion collisions

The global polarization of {\Lambda} hyperons along the total orbital angular momentum of a relativistic heavy-ion collision is presented based on the high statistics data samples collected in Au+Au collisions at \sqrt{s_{NN}} = 2.4 GeV and Ag+Ag at 2.55 GeV with the High-Acceptance Di-Electron Spectrometer (HADES) at GSI, Darmstadt. This is the first measurement below the strangeness production threshold in nucleon-nucleon collisions. Results are reported as a function of the collision centrality as well as a function of the hyperon transverse momentum (p_T) and rapidity (y_{CM}) for the range of centrality 0--40%. We observe a strong centrality dependence of the polarization with an increasing signal towards peripheral collisions. For mid-central (20--40%) collisions the polarization magnitudes are (%) = 6.0 \pm 1.3 (stat.) \pm 2.0 (syst.) for Au+Au and (%) = 4.6 \pm 0.4 (stat.) \pm 0.5 (syst.) for Ag+Ag, which are the largest values observed so far. This observation thus provides a continuation of the increasing trend previously observed by STAR and contrasts expectations from recent theoretical calculations predicting a maximum in the region of collision energies about 3 GeV. The observed polarization is of a similar magnitude as predicted by 3D fluid dynamics and the UrQMD plus thermal vorticity model and significantly above results from the AMPT model.Comment: 8 pages, 4 figure

Inclusive e+^+e−^- production in collisions of pions with protons and nuclei in the second resonance region of baryons

Inclusive e$^+$e$^-$ production has been studied with HADES in $\pi^-$ + p, $\pi^-$ + C and $\pi^- + \mathrm{CH}_2$ reactions, using the GSI pion beam at $\sqrt{s_{\pi p}}$ = 1.49 GeV. Invariant mass and transverse momentum distributions have been measured and reveal contributions from Dalitz decays of $\pi^0$, $\eta$ mesons and baryon resonances. The transverse momentum distributions are very sensitive to the underlying kinematics of the various processes. The baryon contribution exhibits a deviation up to a factor seven from the QED reference expected for the dielectron decay of a hypothetical point-like baryon with the production cross section constrained from the inverse $\gamma$ n$\rightarrow \pi^-$ p reaction. The enhancement is attributed to a strong four-momentum squared dependence of the time-like electromagnetic transition form factors as suggested by Vector Meson Dominance (VMD). Two versions of the VMD, that differ in the photon-baryon coupling, have been applied in simulations and compared to data. VMD1 (or two-component VMD) assumes a coupling via the $\rho$ meson and a direct coupling of the photon, while in VMD2 (or strict VMD) the coupling is only mediated via the $\rho$ meson. The VMD2 model, frequently used in transport calculations for dilepton decays, is found to overestimate the measured dielectron yields, while a good description of the data can be obtained with the VMD1 model assuming no phase difference between the two amplitudes. Similar descriptions have also been obtained using a time-like baryon transition form factor model where the pion cloud plays the major role.Comment: (HADES collaboration

Impact of the Coulomb field on charged-pion spectra in few-GeV heavy-ion collisions

In nuclear collisions the incident protons generate a Coulomb field which acts on produced charged particles. The impact of these interactions on charged-pion transverse-mass and rapidity spectra, as well as on pion–pion momentum correlations is investigated in Au + Au collisions at $\sqrt{^{S}NN}$ = 2.4 GeV. We show that the low-m$_{t}$ region (m$_{t}$ < 0.2 GeV / c$^{2}$) can be well described with a Coulomb-modified Boltzmann distribution that also takes changes of the Coulomb field during the expansion of the fireball into account. The observed centrality dependence of the fitted mean Coulomb potential energy deviates strongly from a $A_{part}^{2/3}$ scaling, indicating that, next to the fireball, the non-interacting charged spectators have to be taken into account. For the most central collisions, the Coulomb modifications of the HBT source radii are found to be consistent with the potential extracted from the single-pion transverse-mass distributions. This finding suggests that the region of homogeneity obtained from two-pion correlations coincides with the region in which the pions freeze-out. Using the inferred mean-square radius of the charge distribution at freeze-out, we have deduced a baryon density, in fair agreement with values obtained from statistical hadronization model fits to the particle yields

The antiproton interaction with an internal 12C target inside the HESR ring at FAIR

In order to fulfill the goal of producing higher rates of doubly strange hyperons, the ¯PANDA collaboration will use the antiproton ring HESR at the future facility FAIR. The low energy hyperon production by an antiproton beam requires to insert a solid target inside the ring. Unwanted side effects of such an insertion are the overwhelming amount of annihilations, which would make the detectors blind, and the fast depletion of the bunch, which circulates inside the ring. The choice of the target material impacts the hyperon production yield: Carbon turned out to provide enough initial hyperon deceleration and keep secondary interactions below a tolerable level. The use of a very thin Diamond target, together with beam steering techniques, seems to be a satisfactory solution to the above problems and will be described hereafter

Comparison of environmental test approaches through MAT€D AIV data and reference to ECSS

The verification effectiveness can be improved with a proper knowledge management, collecting and analyzing data coming from the AIV activities and flight operations of former projects. The ESA Model And Test Effectiveness Database (MAT€D) can be used for this purpose, collecting such data and providing associated statistical analyses to derive feedback for the improvement of the Model and Test Philosophies of future projects. This paper presents a methodology to support analysis of MAT€D data, with the purpose of comparing verification processes of different projects, with a specific emphasis on the environmental tests effectiveness. The used approaches are compared with those reported for each stage and level in ECSS-E-ST-10-03 (Testing). Performed AIV activities, related conditions (e.g. duration, levels) at different stages are considered to build a complexity index framework, and related normalization and aggregation functions are discussed. The related "Test Depth Index" (TDI) is proposed as an innovative method to calculate the completeness of the testing activity in relation to the ECSS standards, as a formal complement to the index currently used in MAT€D, namely MATEI (Model And Test Effectiveness Index). The application to a subset of MAT€D data is presented and recommendations are provided for further improvements

Comparison of Environmental Test Approaches Trough MAT€D AIV Data and Reference to ECSS

The verification effectiveness can be improved with a proper knowledge management, collecting and analyzing data coming from the AIV activities and flight operations of former projects. The ESA Model And Test Effectiveness Database (MAT€D) can be used for this purpose, collecting such data and providing associated statistical analyses to derive feedback for the improvement of the Model and Test Philosophies of future projects. This paper presents a methodology to support analysis of MAT€D data, with the purpose of comparing verification processes of different projects, with a specific emphasis on the environmental tests effectiveness. The used approaches are compared with those reported for each stage and level in ECSS-E-ST-10-03 (Testing). Performed AIV activities, related conditions (e.g. duration, levels) at different stages are considered to build a complexity index framework, and related normalization and aggregation functions are discussed. The related “Test Depth Index” (TDI) is proposed as an innovative method to calculate the completeness of the testing activity in relation to the ECSS standards, as a formal complement to the index currently used in MAT€D, namely MATEI (Model And Test Effectiveness Index). The application to a subset of MAT€D data is presented and recommendations are provided for further improvements