A multi-detector array for high energy nuclear e+e- pair spectrosocopy

A multi-detector array has been constructed for the simultaneous measurement of energy- and angular correlation of electron-positron pairs produced in internal pair conversion (IPC) of nuclear transitions up to 18 MeV. The response functions of the individual detectors have been measured with mono-energetic beams of electrons. Experimental results obtained with 1.6 MeV protons on targets containing $^{11}$B and $^{19}$F show clear IPC over a wide angular range. A comparison with GEANT simulations demonstrates that angular correlations of $e^+e^-$ pairs of transitions in the energy range between 6 and 18 MeV can be determined with sufficient resolution and efficiency to search for deviations from IPC due to the creation and subsequent decay into $e^+e^-$ of a hypothetical short-lived neutral boson.Comment: 20 pages, 8 figure

The Chromospheric Telescope

We introduce the Chromospheric Telescope (ChroTel) at the Observatorio del Teide in Izana on Tenerife as a new multi-wavelength imaging telescope for full-disk synoptic observations of the solar chromosphere. We describe the design of the instrument and summarize its performance during the first one and a half years of operation. We present a method to derive line-of-sight velocity maps of the full solar disk from filtergrams taken in and near the He I infrared line at 10830 \AA.Comment: 12 pages, 9 figure

Comparison of Solar Fine Structure Observed Simultaneously in Ly-{\alpha} and Mg II h

The Chromospheric Lyman Alpha Spectropolarimeter (CLASP) observed the Sun in H I Lyman-{\alpha} during a suborbital rocket flight on September 3, 2015. The Interface Region Imaging Telescope (IRIS) coordinated with the CLASP observations and recorded nearly simultaneous and co-spatial observations in the Mg II h&k lines. The Mg II h and Ly-{\alpha} lines are important transitions, energetically and diagnostically, in the chromosphere. The canonical solar atmosphere model predicts that these lines form in close proximity to each other and so we expect that the line profiles will exhibit similar variability. In this analysis, we present these coordinated observations and discuss how the two profiles compare over a region of quiet sun at viewing angles that approach the limb. In addition to the observations, we synthesize both line profiles using a 3D radiation-MHD simulation. In the observations, we find that the peak width and the peak intensities are well correlated between the lines. For the simulation, we do not find the same relationship. We have attempted to mitigate the instrumental differences between IRIS and CLASP and to reproduce the instrumental factors in the synthetic profiles. The model indicates that formation heights of the lines differ in a somewhat regular fashion related to magnetic geometry. This variation explains to some degree the lack of correlation, observed and synthesized, between Mg II and Ly-{\alpha}. Our analysis will aid in the definition of future observatories that aim to link dynamics in the chromosphere and transition region.Comment: Accepted by Ap

Magnetic fields of opposite polarity in sunspot penumbrae

Context. A significant part of the penumbral magnetic field returns below the surface in the very deep photosphere. For lines in the visible, a large portion of this return field can only be detected indirectly by studying its imprints on strongly asymmetric and three-lobed Stokes V profiles. Infrared lines probe a narrow layer in the very deep photosphere, providing the possibility of directly measuring the orientation of magnetic fields close to the solar surface. Aims. We study the topology of the penumbral magnetic field in the lower photosphere, focusing on regions where it returns below the surface. Methods. We analyzed 71 spectropolarimetric datasets from Hinode and from the GREGOR infrared spectrograph. We inferred the quality and polarimetric accuracy of the infrared data after applying several reduction steps. Techniques of spectral inversion and forward synthesis were used to test the detection algorithm. We compared the morphology and the fractional penumbral area covered by reversed-polarity and three-lobed Stokes V profiles for sunspots at disk center. We determined the amount of reversed-polarity and three-lobed Stokes V profiles in visible and infrared data of sunspots at various heliocentric angles. From the results, we computed center-to-limb variation curves, which were interpreted in the context of existing penumbral models. Results. Observations in visible and near-infrared spectral lines yield a significant difference in the penumbral area covered by magnetic fields of opposite polarity. In the infrared, the number of reversed-polarity Stokes V profiles is smaller by a factor of two than in the visible. For three-lobed Stokes V profiles the numbers differ by up to an order of magnitude.Comment: 11 pages 10 figures plus appendix (2 pages 3 figures). Accepted as part of the A&A special issue on the GREGOR solar telescop

Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies

Natural Image Coding in V1: How Much Use is Orientation Selectivity?

Orientation selectivity is the most striking feature of simple cell coding in V1 which has been shown to emerge from the reduction of higher-order correlations in natural images in a large variety of statistical image models. The most parsimonious one among these models is linear Independent Component Analysis (ICA), whereas second-order decorrelation transformations such as Principal Component Analysis (PCA) do not yield oriented filters. Because of this finding it has been suggested that the emergence of orientation selectivity may be explained by higher-order redundancy reduction. In order to assess the tenability of this hypothesis, it is an important empirical question how much more redundancies can be removed with ICA in comparison to PCA, or other second-order decorrelation methods. This question has not yet been settled, as over the last ten years contradicting results have been reported ranging from less than five to more than hundred percent extra gain for ICA. Here, we aim at resolving this conflict by presenting a very careful and comprehensive analysis using three evaluation criteria related to redundancy reduction: In addition to the multi-information and the average log-loss we compute, for the first time, complete rate-distortion curves for ICA in comparison with PCA. Without exception, we find that the advantage of the ICA filters is surprisingly small. Furthermore, we show that a simple spherically symmetric distribution with only two parameters can fit the data even better than the probabilistic model underlying ICA. Since spherically symmetric models are agnostic with respect to the specific filter shapes, we conlude that orientation selectivity is unlikely to play a critical role for redundancy reduction

CLASP2: The Chromospheric LAyer Spectro-Polarimeter

A major remaining challenge for heliophysicsis to decipher the magnetic structure of the chromosphere, due to its "large role in defining how energy is transported into the corona and solar wind" (NASA's Heliophysics Roadmap). Recent observational advances enabled by the Interface Region Imaging Spectrometer (IRIS) have revolutionized our view of the critical role this highly dynamic interface between the photosphere and corona plays in energizing and structuring the outer solar atmosphere. Despite these advances, a major impediment to better understanding the solar atmosphere is our lack of empirical knowledge regarding the direction and strength of the magnetic field in the upper chromosphere. Such measurements are crucial to address several major unresolved issues in solar physics: for example, to constrain the energy flux carried by the Alfven waves propagating through the chromosphere (De Pontieuet al., 2014), and to determine the height at which the plasma Beta = 1 transition occurs, which has important consequences for the braiding of magnetic fields (Cirtainet al., 2013; Guerreiroet al., 2014), for propagation and mode conversion of waves (Tian et al., 2014a; Straus et al., 2008) and for non-linear force-free extrapolation methods that are key to determining what drives instabilities such as flares or coronal mass ejections (e.g.,De Rosa et al., 2009). The most reliable method used to determine the solar magnetic field vector is the observation and interpretation of polarization signals in spectral lines, associated with the Zeeman and Hanle effects. Magnetically sensitive ultraviolet spectral lines formed in the upper chromosphere and transition region provide a powerful tool with which to probe this key boundary region (e.g., Trujillo Bueno, 2014). Probing the magnetic nature of the chromosphere requires measurement of the Stokes I, Q, U and V profiles of the relevant spectral lines (of which Q, U and V encode the magnetic field information)

Pairwise maximum entropy models for studying large biological systems: when they can and when they can't work

One of the most critical problems we face in the study of biological systems is building accurate statistical descriptions of them. This problem has been particularly challenging because biological systems typically contain large numbers of interacting elements, which precludes the use of standard brute force approaches. Recently, though, several groups have reported that there may be an alternate strategy. The reports show that reliable statistical models can be built without knowledge of all the interactions in a system; instead, pairwise interactions can suffice. These findings, however, are based on the analysis of small subsystems. Here we ask whether the observations will generalize to systems of realistic size, that is, whether pairwise models will provide reliable descriptions of true biological systems. Our results show that, in most cases, they will not. The reason is that there is a crossover in the predictive power of pairwise models: If the size of the subsystem is below the crossover point, then the results have no predictive power for large systems. If the size is above the crossover point, the results do have predictive power. This work thus provides a general framework for determining the extent to which pairwise models can be used to predict the behavior of whole biological systems. Applied to neural data, the size of most systems studied so far is below the crossover point

Current status of haploidentical stem cell transplantation for leukemia

Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy

Are Metastases from Metastases Clinical Relevant? Computer Modelling of Cancer Spread in a Case of Hepatocellular Carcinoma

Background: Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. Methods: The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. Results: The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient’s death. Conclusion: The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e.