FGF dependent regulation of Zfhx1b gene expression promotes the formation of definitive neural stem cells in the mouse anterior neurectoderm

<p>Abstract</p> <p>Background</p> <p>Mouse definitive neural stem cells (NSCs) are derived from a population of LIF-responsive primitive neural stem cells (pNSCs) within the neurectoderm, yet details on the early signaling and transcriptional mechanisms that control this lineage transition are lacking. Here we tested whether FGF and Wnt signaling pathways can regulate <it>Zfhx1b </it>expression to control early neural stem cell development.</p> <p>Results</p> <p>By microinjecting FGF8b into the pro-amniotic cavity <it>ex vivo </it>at 7.0 days post-coitum (dpc) and culturing whole embryos, we demonstrate that neurectoderm-specific gene expression (for example, <it>Sox2</it>, <it>Nestin</it>, <it>Zfhx1b</it>) is increased, whereas Wnt3a represses neurectoderm gene expression. To determine whether FGF signaling also mediates the lineage transition from a pNSC to a NSC, 7.0-dpc embryos were microinjected with either FGF8b or inhibitors of the FGF receptor-MAP kinase signaling pathway <it>ex vivo</it>, cultured as whole embryos to approximately 8.5 dpc and assayed for clonal NSC colony formation. We show that pre-activation of FGF signaling in the anterior neurectoderm causes an increase in the number of colony forming NSCs derived later from the anterior neural plate, whereas inhibition of FGF signaling significantly reduces the number of NSC colonies. Interestingly, inhibition of FGF signaling causes the persistence of LIF-responsive pNSCs within the anterior neural plate and over-expression of <it>Zfhx1b </it>in these cells is sufficient to rescue the transition from a LIF-responsive pNSC to an FGF-responsive NSC.</p> <p>Conclusion</p> <p>Our data suggest that definitive NSC fate specification in the mouse neurectoderm is facilitated by FGF activation of <it>Zfhx1b</it>.</p

Step-wise responses in mesoscopic glassy systems: a mean field approach

We study statistical properties of peculiar responses in glassy systems at mesoscopic scales based on a class of mean-field spin-glass models which exhibit 1 step replica symmetry breaking. Under variation of a generic external field, a finite-sized sample of such a system exhibits a series of step wise responses which can be regarded as a finger print of the sample. We study in detail the statistical properties of the step structures based on a low temperature expansion approach and a replica approach. The spacings between the steps vanish in the thermodynamic limit so that arbitrary small but finite variation of the field induce infinitely many level crossings in the thermodynamic limit leading to a static chaos effect which yields a self-averaging, smooth macroscopic response. We also note that there is a strong analogy between the problem of step-wise responses in glassy systems at mesoscopic scales and intermittency in turbulent flows due to shocks.Comment: 50 pages, 18 figures, revised versio

Roughness of Microspheres for Force Measurements

We have investigated the morphology and surface roughness of several commercially available microspheres to determine their suitability for force measurements using the atomic force microscope. The roughness varies considerably, depending on sphere size and material, ranging from nearly ideally flat up to micrometer-sized features. Because surface roughness significantly influences the magnitude and accuracy of measurement of surface forces, the results presented here should be helpful for colloid physicists and in particular for those performing force measurements

The VLT-FLAMES Tarantula Survey. IX. The interstellar medium seen through Diffuse Interstellar Bands and neutral sodium

The Tarantula Nebula (30 Dor) is a spectacular star-forming region in the Large Magellanic Cloud, seen through gas in the Galactic Disc and Halo. Diffuse Interstellar Bands offer a unique probe of the diffuse, cool-warm gas in these regions. The aim is to use DIBs as diagnostics of the local interstellar conditions, whilst at the same time deriving properties of the yet-unknown carriers. Spectra of over 800 early-type stars from the VLT Flames Tarantula Survey (VFTS) were analysed. Maps were created, separately, for the Galactic and LMC absorption in the DIBs at 4428 and 6614 Ang and - in a smaller region near the central cluster R136 - neutral sodium (Na I D); we also measured the DIBs at 5780 and 5797 Ang. The maps show strong 4428 and 6614 Ang DIBs in the quiescent cloud complex to the south of 30 Dor but weak absorption in the harsher environments to the north (bubbles) and near the OB associations. The Na maps show at least five kinematic components in the LMC and a shell-like structure surrounding R136, and small-scale structure in the Milky Way. The strengths of the 4428, 5780, 5797 and 6614 Ang DIBs are correlated, also with Na absorption and visual extinction. The strong 4428 Ang DIB is present already at low Na column density but the 6614, 5780 and 5797 Ang DIBs start to be detectable at subsequently larger Na column densities. The relative strength of the 5780 and 5797 Ang DIBs clearly confirm the Tarantula Nebula and Galactic high-latitude gas to represent a harsh radiation environment. The resilience of the 4428 Ang DIB suggests its carrier is large, compact and neutral. Structure is detected in the distribution of cool-warm gas on scales between one and >100 pc in the LMC and as little as 0.01 pc in the Sun's vicinity. Stellar winds from the central cluster R136 have created an expanding shell; some infalling gas is also detected, reminiscent of a galactic "fountain".Comment: Accepted for publication in Astronomy and Astrophysic

Lentigo maligna - anatomic location as a potential risk factor for recurrences after non-surgical treatment

Background: A higher incidence of lentigo maligna (LM) recurrences on the nose was previously observed in our cohort after non-surgical treatment. Objectives: To determine histological parameters that might be related to the previously observed higher incidence of LM recurrences on the nose after non-surgical treatment. Methods: We randomly selected 22 surgical specimens of LM on the nose and 22 on the cheek. Histopathological analysis was performed on haematoxylin and eosin stained and microphthalmia transcription factor immunohistochemically stained slides. The number of pilosebaceous units (PSU) per mm, maximum depth of atypical melanocytes along the skin appendages and maximum depth of the PSU itself were determined. Results: The nose had a significantly higher density of PSU than the cheek. The atypical melanocytes extended deeper along the PSU on the nose with a mean (SD) depth of 1.29 mm (0.48)

Heavy quark flavour dependence of multiparticle production in QCD jets

After inserting the heavy quark mass dependence into QCD partonic evolution equations, we determine the mean charged hadron multiplicity and second multiplicity correlators of jets produced in high energy collisions. We thereby extend the so-called dead cone effect to the phenomenology of multiparticle production in QCD jets and find that the average multiplicity of heavy-quark initiated jets decreases significantly as compared to the massless case, even taking into account the weak decay products of the leading primary quark. We emphasize the relevance of our study as a complementary check of $b$-tagging techniques at hadron colliders like the Tevatron and the LHC.Comment: Version revised, accepted for publication in JHEP, 21 pages and 7 figure

Soft-core hyperon-nucleon potentials

A new Nijmegen soft-core OBE potential model is presented for the low-energy YN interactions. Besides the results for the fit to the scattering data, which largely defines the model, we also present some applications to hypernuclear systems using the G-matrix method. An important innovation with respect to the original soft-core potential is the assignment of the cut-off masses for the baryon-baryon-meson (BBM) vertices in accordance with broken SU(3)$_F$, which serves to connect the NN and the YN channels. As a novel feature, we allow for medium strong breaking of the coupling constants, using the $^3P_0$ model with a Gell-Mann--Okubo hypercharge breaking for the BBM coupling. We present six hyperon-nucleon potentials which describe the available YN cross section data equally well, but which exhibit some differences on a more detailed level. The differences are constructed such that the models encompass a range of scattering lengths in the $\Sigma N$ and $\Lambda N$ channels. For the scalar-meson mixing angle we obtained values $\theta_S=37$ to 40 degrees, which points to almost ideal mixing angles for the scalar $q\bar{q}$ states. The G-matrix results indicate that the remarkably different spin-spin terms of the six potentials appear specifically in the energy spectra of $\Lambda$ hypernuclei.Comment: 37 pages, 4 figure

Complaints handling in hospitals: an empirical study of discrepancies between patients' expectations and their experiences

<p>Abstract</p> <p>Background</p> <p>Many patients are dissatisfied with the way in which their complaints about health care are dealt with. This study tested the assumption that this dissatisfaction consists – in part at least – of unmet expectations.</p> <p>Methods</p> <p>Subjects were 279 patients who lodged a complaint with the complaints committees of 74 hospitals in the Netherlands. They completed two questionnaires; one on their expectations at the start of the complaints handling process, and one on their experiences after the complaints procedure (pre-post design; response 50%). Dependent variables are patients' satisfaction and their feeling that justice was done; independent variables are the association between patients' expectations and their experiences.</p> <p>Results</p> <p>Only 31% of the patients felt they had received justice from the complaints process.</p> <p>Two thirds of the patients were satisfied with the conduct of the complaints committee, but fewer were satisfied with the conduct of the hospital or the medical professional (29% and 18%). Large discrepancies between expectations and experiences were found in the case of doctors not admitting errors when errors had been made, and of hospital managements not providing information on corrective measures that were taken. Discrepancies collectively explained 51% of patients' dissatisfaction with the committee and one third of patients' dissatisfaction with the hospital and the professional. The feeling that justice was done was influenced by the decision on the complaint (well-founded or not), but also by the satisfaction with the conduct of the committee, the hospital management and the professional involved.</p> <p>Conclusion</p> <p>It is disappointing to observe that less than one third of the patients felt that justice had been done through the complaints handling process. This study shows that the feeling that justice had been done is not only influenced by the judgement of the complaints committee, but also by the response of the professional. Furthermore, hospitals and professionals should communicate on how they are going to prevent a recurrence of the events that led to the complaint.</p