Targeted disruption of the MHC class II Aa gene in C57BL/6 mice

The MHC class II gene Aa was disrupted by targeted mutation in embryonic stem (ES) cells derived from C57BL/6 mice to prevent expression of MHC class II molecules. Contrary to previous reports, the effect of the null-mutation on T cell development was investigated in C57BL/6 mice, which provide a defined genetic background. The complete lack of cell surface expression of MHC class II molecules in B6-Aa0/Aa0 homozygous mutant mice was directly demonstrated by cytofiuorometric analysis using anti-Ab and anti-la specific mAbs. Development of CD4+CD8− T cells in the thymus was largely absent except for a small population of thymocytes expressing high levels of CD4 together with low amounts of CD8. The majority of these cells express the TCR at high density. Although mature CD4+CD8− T cells were undetectable in the thymus, some T cells with a CD4+CD8−TCRhigh phenotype were found in lymph nodes and spleen. Peripheral T cells from themutant mice can be polyclonally activated in vitro with the mitogen concanavalin A. However, they could not be stimulated with staphylococcal enterotoxin B in autologous lymphocyte reactions, thereby demonstrating the absence of MHC class II expression in these mice. Peripheral B cells in B6-Aa0/Aa0 mutants were functional and responded to the T cell independent antigen levan by the production of antigenspecific IgM antibodies similar to wild-type cells. The B6-Aa0/Aa0 mutant mice described in this study represent an important tool to investigate the involvement of MHC class II molecules in lymphocyte maturation and the immune respons

Functional expression of a human TCRβ gene in transgenic mice

A functionally rearranged TCRβ (Tcrb) gene was isolated from a cloned human T helper cell recognizing the CS.T3 epitope of Plasmodium falciparum with HLA-DR2. Transgenic mice were generated by co-injection of the human gene together with the mouse Tcrb enhancer. Analysis of transgenic mice shows that the functional Tcrb gene of xenogenic, i.e. human, origin exerts allelic exclusion of endogenous Tcrb genes. Cytofluorometric analysis revealed expression of the human TCRβ chain on virtually all thymocytes and peripheral T cells together with endogenous TCRβ chains and CD3 components. No surface expression of mouse TCRβ chain or rearrangement of endogenous Tcr genes was detectable. Expression of the hybrid receptor causes a reduction in the number of thymocytes and a bias for CD4+CD8− T cells in the thymus as compared with non-transgenic littermates. Peripheral transgenic T cells mount a normal prollferative response against allogenelc targets in mixed lymphocyte reactions. These results show that a hybrid mouse/human TCR is able to pass positive and negative selection in the thymus, and is functional in transgenic mic

Under-shelf ice foraging of Weddell seals

The Weddell seal (Leptonychotes weddellii) inhabits the Antarctic coastal ecosystem and aggregates in areas characterized by a stable fast ice layer. Due to their extreme diving capabilities, they are able to exploit both pelagic and benthic prey resources. They mainly feed on fishes but occasionally also take cephalopods and crustaceans. Weddell seals instrumented with still-picture camera loggers in the Drescher Inlet, eastern Weddell Sea, detected an unknown cryo-benthic community underneath the floating ice shelf. Images show dense aggregations of invertebrates that likely represent an attractive food horizon for Weddell seals. In this context, we conducted a retrospective analysis of dive profiles collected in the Drescher Inlet to identify favoured hunting depths of Weddell seals and correlate those to the local physical and biological environment. A total of 34 adult Weddell seals were instrumented with dive loggers in the course of six summer field campaigns between 1990 and 2016. An automated broken stick algorithm was used to separate each dive profile into different segments. Segments with a high sinuosity were considered to indicate hunting. Segments characterized by a straight dive trajectories (low sinuosity), were assumed to be transit phases with no hunting activities. A tri-modal distribution of mean hunting depths suggests that Weddell seals concentrated their foraging activities in three depth strata. A peak in hunting depths below 370 m corresponds to the sea floor of the Drescher Inlet, indicating demersal foraging. A second peak between 110 and 160 m matches with the depth of the underside of the floating ice shelf, which suggests shelf ice associated foraging. The third peak probably represents hunting in the pelagic realm. Our investigation highlights the importance of the shelf ice underside as an attractive food horizon for Weddell seals suggesting a re-evaluation of trophic interactions and bentho-pelagic processes in the coastal Antarctic ecosystem

LOFAR Sparse Image Reconstruction

Context. The LOw Frequency ARray (LOFAR) radio telescope is a giant digital phased array interferometer with multiple antennas distributed in Europe. It provides discrete sets of Fourier components of the sky brightness. Recovering the original brightness distribution with aperture synthesis forms an inverse problem that can be solved by various deconvolution and minimization methods Aims. Recent papers have established a clear link between the discrete nature of radio interferometry measurement and the "compressed sensing" (CS) theory, which supports sparse reconstruction methods to form an image from the measured visibilities. Empowered by proximal theory, CS offers a sound framework for efficient global minimization and sparse data representation using fast algorithms. Combined with instrumental direction-dependent effects (DDE) in the scope of a real instrument, we developed and validated a new method based on this framework Methods. We implemented a sparse reconstruction method in the standard LOFAR imaging tool and compared the photometric and resolution performance of this new imager with that of CLEAN-based methods (CLEAN and MS-CLEAN) with simulated and real LOFAR data Results. We show that i) sparse reconstruction performs as well as CLEAN in recovering the flux of point sources; ii) performs much better on extended objects (the root mean square error is reduced by a factor of up to 10); and iii) provides a solution with an effective angular resolution 2-3 times better than the CLEAN images. Conclusions. Sparse recovery gives a correct photometry on high dynamic and wide-field images and improved realistic structures of extended sources (of simulated and real LOFAR datasets). This sparse reconstruction method is compatible with modern interferometric imagers that handle DDE corrections (A- and W-projections) required for current and future instruments such as LOFAR and SKAComment: Published in A&A, 19 pages, 9 figure

The ACA training programme to improve communication between general practitioners and their palliative care patients: development and applicability

<p>Abstract</p> <p>We describe the development of a new training programme on GP-patient communication in palliative care, and the applicability to GPs and GP Trainees. This ‘ACA training programme’ focuses on <b> <it>A</it> </b><it>vailability</it> of the GP for the patient, <b> <it>C</it> </b><it>urrent issues</it> that should be raised by the GP, and <b> <it>A</it> </b><it>nticipating</it> various scenarios. Evaluation results indicate the ACA training programme to be applicable to GPs and GP Trainees. The ACA checklist was appreciated by GPs as useful both in practice and as a learning tool, whereas GP Trainees mainly appreciated the list for use in practice.</p

Raising positive expectations helps patients with minor ailments: A cross-sectional study

Background: Consultations for minor ailments constitute a large part of the workload of general practitioners (GPs). As medical interventions are not always available, specific communication strategies, such as active listening and positive communication, might help GPs to handle these problems adequately. This study examines to what extent GPs display both strategies during consultations for minor ailments and investigates how each of these relate to the patients' perceived health, consultation frequency and medication adherence. Methods: 524 videotaped consultations between Dutch GPs and patients aged 18 years or older were selected. All patients presented a minor ailment, and none of them suffered from a diagnosed chronic illness. The observation protocol included the validated Active Listening Observation Scale (ALOS-global), as well as three domains of positive communication, i.e. providing reassurance, a clear explanation, and a favourable prognosis. Patients completed several questionnaires before, immediately after, and two weeks after the consultation. These included measures for state anxiety (STAI), functional health status (COOP/ WONCA charts) and medication adherence (MAQ). Consultation frequency was available from an ongoing patient registration. Data were analysed using multivariate regression analyses. Results: Reassurance was related to patients' better overall health. Providing a favourable prognosis was linked to patients feeling better, but only when accompanied by a clear explanation of the complaints. A clear explanation was also related to patients feeling better and less anxious, except when patients reported a low mood pre-visit. Active listening alone was positively associated with patients feeling worse. Among patients in a good mood state, active listening was associated with less adherence. Conclusion: To some extent, it seems helpful when GPs are at the same time clear and optimistic about the nature and course of minor ailments. Yet, it does not seem helpful always and in all cases, e.g. when patients feel low upon entering the consulting room. Although communication strategies might to some extent contribute to the management of minor ailments, the results of this observational study also indicate that it is important for a physician to pay attention to the mood of the patient who enters the consulting room. (aut. ref.

Cassiopeia A, Cygnus A, Taurus A, and Virgo A at ultra-low radio frequencies

Context. The four persistent radio sources in the northern sky with the highest flux density at metre wavelengths are Cassiopeia A, Cygnus A, Taurus A, and Virgo A; collectively they are called the A-team. Their flux densities at ultra-low frequencies (&lt; 100 MHz) can reach several thousands of janskys, and they often contaminate observations of the low-frequency sky by interfering with image processing. Furthermore, these sources are foreground objects for all-sky observations hampering the study of faint signals, such as the cosmological 21 cm line from the epoch of reionisation. Aims. We aim to produce robust models for the surface brightness emission as a function of frequency for the A-team sources at ultra-low frequencies. These models are needed for the calibration and imaging of wide-area surveys of the sky with low-frequency interferometers. This requires obtaining images at an angular resolution better than 15\u2033 with a high dynamic range and good image fidelity. Methods. We observed the A-team with the Low Frequency Array (LOFAR) at frequencies between 30 MHz and 77 MHz using the Low Band Antenna system. We reduced the datasets and obtained an image for each A-team source. Results. The paper presents the best models to date for the sources Cassiopeia A, Cygnus A, Taurus A, and Virgo A between 30 MHz and 77 MHz. We were able to obtain the aimed resolution and dynamic range in all cases. Owing to its compactness and complexity, observations with the long baselines of the International LOFAR Telescope will be required to improve the source model for Cygnus A further

Low-frequency radio absorption in Cassiopeia A

Cassiopeia A is one of the best-studied supernova remnants. Its shocked ejecta emits brightly in radio and X-rays. Its unshocked ejecta can be studied through infrared emission, the radio-active decay of $^{44}$Ti, and low frequency free-free absorption due to cold gas internal to the shell. Free-free absorption is affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies constrain a combination of these properties. We use LOFAR LBA observations at 30-77 MHz and L-band VLA observations to compare $u-v$-matched images with a common resolution of 17". We simultaneously fit, per pixel, for the emission measure and the ratio of the emission from the unabsorbed front of the shell versus the absorbed back of the shell. We explore the effects that low temperatures and a high degree of clumping can have on the derived physical properties, such as mass and density. We also compile published radio flux measurements, fit for the absorption processes that occur in the radio band, and consider how they affect the secular decline of the source. We find a mass in the unshocked ejecta of $M = 2.95 \pm {0.48} \,M_{\odot}$ for an assumed gas temperature of $T=100$ K. This estimate is reduced for colder gas temperatures and if the ejecta are clumped. We measure the reverse shock to have a radius of $114$" $\pm$6". We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low frequency behaviour of the secular decline rate. To reconcile our low frequency absorption measurements with models that predict little mass in the unshocked ejecta we need the ejecta to be very clumped, or the temperature in the cold gas to be low ($\sim10$ K). Both conditions can jointly contribute to the high absorption.Comment: Accepted for publication in A&A v2: including the DOI, language edit

LOFAR MSSS: Detection of a low-frequency radio transient in 400 hrs of monitoring of the North Celestial Pole

We present the results of a four-month campaign searching for low-frequency radio transients near the North Celestial Pole with the Low-Frequency Array (LOFAR), as part of the Multifrequency Snapshot Sky Survey (MSSS). The data were recorded between 2011 December and 2012 April and comprised 2149 11-minute snapshots, each covering 175 deg^2. We have found one convincing candidate astrophysical transient, with a duration of a few minutes and a flux density at 60 MHz of 15-25 Jy. The transient does not repeat and has no obvious optical or high-energy counterpart, as a result of which its nature is unclear. The detection of this event implies a transient rate at 60 MHz of 3.9 (+14.7, -3.7) x 10^-4 day^-1 deg^-2, and a transient surface density of 1.5 x 10^-5 deg^-2, at a 7.9-Jy limiting flux density and ~10-minute time-scale. The campaign data were also searched for transients at a range of other time-scales, from 0.5 to 297 min, which allowed us to place a range of limits on transient rates at 60 MHz as a function of observation duration.Peer reviewedFinal Accepted Versio