Regulation of 130kDa smooth muscle myosin light chain kinase expression by an intronic CArG element

The mylk1 gene encodes a 220-kDa nonmuscle myosin light chain kinase (MLCK), a 130-kDa smooth muscle MLCK (smMLCK), as well as the non-catalytic product telokin. Together, these proteins play critical roles in regulating smooth muscle contractility. Changes in their expression are associated with many pathological conditions; thus, it is important to understand the mechanisms regulating expression of mylk1 gene transcripts. Previously, we reported a highly conserved CArG box, which binds serum response factor, in intron 15 of mylk1. Because this CArG element is near the promoter that drives transcription of the 130-kDa smMLCK, we examined its role in regulating expression of this transcript. Results show that deletion of the intronic CArG region from a β-galactosidase reporter gene abolished transgene expression in mice in vivo. Deletion of the CArG region from the endogenous mylk1 gene, specifically in smooth muscle cells, decreased expression of the 130-kDa smMLCK by 40% without affecting expression of the 220-kDa MLCK or telokin. This reduction in 130-kDa smMLCK expression resulted in decreased phosphorylation of myosin light chains, attenuated smooth muscle contractility, and a 24% decrease in small intestine length that was associated with a significant reduction of Ki67-positive smooth muscle cells. Overall, these data show that the CArG element in intron 15 of the mylk1 gene is necessary for maximal expression of the 130-kDa smMLCK and that the 130-kDa smMLCK isoform is specifically required to regulate smooth muscle contractility and small intestine smooth muscle cell proliferation

Error analysis of nuclear mass fits

We discuss the least-square and linear-regression methods, which are relevant for a reliable determination of good nuclear-mass-model parameter sets and their errors. In this perspective, we define exact and inaccurate models and point out differences in using the standard error analyses for them. As an illustration, we use simple analytic models for nuclear binding energies and study the validity and errors of models' parameters, and uncertainties of its mass predictions. In particular, we show explicitly the influence of mass-number dependent weights on uncertainties of liquid-drop global parameters.Comment: 10 RevTeX pages, 9 figures, submitted to Physical Review

Implementing 'universal' access to antiretroviral treatment in South Africa:a scoping review on research priorities

‘Universal’ access to antiretroviral treatment (ART) has become the global standard for treating people living with HIV and achieving epidemic control; yet, findings from numerous ‘test and treat’ trials and implementation studies in sub-Saharan Africa suggest that bringing ‘universal' access to ART to scale is more complex than anticipated. Using South Africa as a case example, we describe the research priorities and foci in the literature on expanded ART access. To do so, we adapted Arksey and O’Malley’s six-stage scoping review framework to describe the peer-reviewed literature and opinion pieces on expanding access to ART in South Africa between 2000 and 2017. Data collection included systematic searches of two databases and hand-searching of a sub-sample of reference lists. We used an adapted socio-ecological thematic framework to categorize data according to where it located the challenges and opportunities of expanded ART eligibility: individual/client, health worker–client relationship, clinic/community context, health systems infrastructure and/or policy context. We included 194 research articles and 23 opinion pieces, of 1512 identified, addressing expanded ART access in South Africa. The peer-reviewed literature focused on the individual and health systems infrastructure; opinion pieces focused on changing roles of individuals, communities and health services implementers. We contextualized our findings through a consultative process with a group of researchers, HIV clinicians and programme managers to consider critical knowledge gaps. Unlike the published literature, the consultative process offered particular insights into the importance of researching and intervening in the relational aspects of HIV service delivery as South Africa’s HIV programme expands. An overwhelming focus on individual and health systems infrastructure factors in the published literature on expanded ART access in South Africa may skew understanding of HIV programme shortfalls away from the relational aspects of HIV services delivery and delay progress with finding ways to leverage non-medical modalities for achieving HIV epidemic control

The AARTFAAC All-Sky Monitor: System Design and Implementation

The Amsterdam-ASTRON Radio Transients Facility And Analysis Center (AARTFAAC) all sky monitor is a sensitive, real time transient detector based on the Low Frequency Array (LOFAR). It generates images of the low frequency radio sky with spatial resolution of 10s of arcmin, MHz bandwidths, and a time cadence of a few seconds, while simultaneously but independently observing with LOFAR. The image timeseries is then monitored for short and bright radio transients. On detection of a transient, a low latency trigger will be generated for LOFAR, which can interrupt its schedule to carry out follow-up observations of the trigger location at high sensitivity and resolutions. In this paper, we describe our heterogeneous, hierarchical design to manage the 240 Gbps raw data rate, and large scale computing to produce real-time images with minimum latency. We discuss the implementation of the instrumentation, its performance, and scalability.Comment: Submitted to Journal of Astronomical Instrumentation, Special issue on 'Digital Signal Processing (DSP) in Radio Astronomy

NPK Bilanzen von ökologischer und konventioneller Landwirtschaft im Vergleich: Ergebnisse eines 35-jährigen Feldversuches

Die Ausreichende Verfügbarkeit von Stickstoff (N), Phosphor (P) und Kalium (K) ist essentiell für einen konstanten Ernteertrag in landwirtschaftlichen Systemen. Im DOK-Versuch in Therwil (Schweiz) wird seit 1978 ein Systemvergleich zwischen ökologischer und konventioneller Landwirtschaft im Rahmen eines Feldversuches betrieben. Die Verfahren biologisch-dynamisch (DYN) und organisch-biologisch (ORG) werden nur mit Stallmist gedüngt, während im konventionellen Verfahren (KON) zusätzlich mit Mineraldünger ausgeglichen wird. Im mineralisch gedüngten Verfahren (MIN) wird nur Mineraldünger ausgebracht, in der ungedüngten Kontrollfläche (NON) erfolgt seit Versuchsbeginn keine Düngung. Die Verfahren DYN, ORG und KON werden auf zwei Düngestufen geführt (2 = praxisübliche Düngung; 1 = halbe praxisübliche Dündung), Verfahren MIN nur auf Düngestufe 2. Ziel der Arbeit war es eine NPK Bilanz für den DOK-Versuch zu errechnen, um eine Abschätzung des Verlustpotentials bzw. von Nährstoffmangel der Feldfrüchte im jeweiligen Bewirtschaftungssystem zu ermöglichen. Die Nährstoffbilanz errechnete sich aus dem Vergleich jährlicher Eintrag minus jährlicher Austrag pro Versuchsparzelle. Berücksichtigte Einträge für die Elemente N, P und K waren: 1) Düngung, 2) Deposition, 3) Saatgut. Für N wurde zusätzlich die 4) symbiotische N-fixierung durch Leguminosen sowie der 5) Transfer von fixiertem N zu Gräsern, basierend auf vorhergehenden Studien im DOK Versuch, geschätzt. Berücksichtigte Austräge für die Elemente N, P und K waren: 6) Entzug durch Ernteprodukte sowie 7) Auswaschungsversluste. Für die Elemente N und P wurden zusätzlich die Bodenvorräte aus jährlichen (N) oder 7-jährlichen (P) Messungen in Ober- und Unterboden errechnet und mit den Ergebnissen der Bilanzierung in Beziehung gesetzt. Die wichtigsten Parameter der Nährstoffbilanzen waren die Faktoren Düngung sowie Entzug durch Ernteprodukte, wobei in der N-Bilanz auch die symbiotische N-fixierung und deren Transfer zu Gräsern eine gewichtige Rolle spielte. Die Ergebnisse der NPK-Bilanzierung deuten auf unterschiedliche Nährstofflimitierungen sowohl im Bezug auf die Verfahren, als auch auf den unterschiedlichen Düngestufen hin. Die Resultate werden in Bezug auf eine nachhaltige Bodennutzung in verschiedenen landwirtschaftlichen Systemen diskutiert

LOFAR tied-array imaging and spectroscopy of solar S bursts

Context. The Sun is an active source of radio emission that is often associated with energetic phenomena ranging from nanoflares to coronal mass ejections (CMEs). At low radio frequencies (<100 MHz), numerous millisecond duration radio bursts have been reported, such as radio spikes or solar S bursts (where S stands for short). To date, these have neither been studied extensively nor imaged because of the instrumental limitations of previous radio telescopes. Aims. Here, LOw Frequency ARray (LOFAR) observations were used to study the spectral and spatial characteristics of a multitude of S bursts, as well as their origin and possible emission mechanisms. Methods. We used 170 simultaneous tied-array beams for spectroscopy and imaging of S bursts. Since S bursts have short timescales and fine frequency structures, high cadence (~50 ms) tied-array images were used instead of standard interferometric imaging, that is currently limited to one image per second. Results. On 9 July 2013, over 3000 S bursts were observed over a time period of ~8 h. S bursts were found to appear as groups of short-lived (<1 s) and narrow-bandwidth (~2.5 MHz) features, the majority drifting at ~3.5 MHz s-1 and a wide range of circular polarisation degrees (2−8 times more polarised than the accompanying Type III bursts). Extrapolation of the photospheric magnetic field using the potential field source surface (PFSS) model suggests that S bursts are associated with a trans-equatorial loop system that connects an active region in the southern hemisphere to a bipolar region of plage in the northern hemisphere. Conclusions. We have identified polarised, short-lived solar radio bursts that have never been imaged before. They are observed at a height and frequency range where plasma emission is the dominant emission mechanism, however, they possess some of the characteristics of electron-cyclotron maser emission

A very brief description of LOFAR - the Low Frequency Array

LOFAR (Low Frequency Array) is an innovative radio telescope optimized for the frequency range 30-240 MHz. The telescope is realized as a phased aperture array without any moving parts. Digital beam forming allows the telescope to point to any part of the sky within a second. Transient buffering makes retrospective imaging of explosive short-term events possible. The scientific focus of LOFAR will initially be on four key science projects (KSPs): 1) detection of the formation of the very first stars and galaxies in the universe during the so-called epoch of reionization by measuring the power spectrum of the neutral hydrogen 21-cm line (Shaver et al. 1999) on the ~5' scale; 2) low-frequency surveys of the sky with of order $10^8$ expected new sources; 3) all-sky monitoring and detection of transient radio sources such as gamma-ray bursts, x-ray binaries, and exo-planets (Farrell et al. 2004); and 4) radio detection of ultra-high energy cosmic rays and neutrinos (Falcke & Gorham 2003) allowing for the first time access to particles beyond 10^21 eV (Scholten et al. 2006). Apart from the KSPs open access for smaller projects is also planned. Here we give a brief description of the telescope.Comment: 2 pages, IAU GA 2006, Highlights of Astronomy, Volume 14, K.A. van der Hucht, e

Imaging Jupiter's radiation belts down to 127 MHz with LOFAR

Context. Observing Jupiter's synchrotron emission from the Earth remains today the sole method to scrutinize the distribution and dynamical behavior of the ultra energetic electrons magnetically trapped around the planet (because in-situ particle data are limited in the inner magnetosphere). Aims. We perform the first resolved and low-frequency imaging of the synchrotron emission with LOFAR at 127 MHz. The radiation comes from low energy electrons (~1-30 MeV) which map a broad region of Jupiter's inner magnetosphere. Methods (see article for complete abstract) Results. The first resolved images of Jupiter's radiation belts at 127-172 MHz are obtained along with total integrated flux densities. They are compared with previous observations at higher frequencies and show a larger extent of the synchrotron emission source (>=4 $R_J$). The asymmetry and the dynamic of east-west emission peaks are measured and the presence of a hot spot at lambda_III=230 {\deg} $\pm$ 25 {\deg}. Spectral flux density measurements are on the low side of previous (unresolved) ones, suggesting a low-frequency turnover and/or time variations of the emission spectrum. Conclusions. LOFAR is a powerful and flexible planetary imager. The observations at 127 MHz depict an extended emission up to ~4-5 planetary radii. The similarities with high frequency results reinforce the conclusion that: i) the magnetic field morphology primarily shapes the brightness distribution of the emission and ii) the radiating electrons are likely radially and latitudinally distributed inside about 2 $R_J$. Nonetheless, the larger extent of the brightness combined with the overall lower flux density, yields new information on Jupiter's electron distribution, that may shed light on the origin and mode of transport of these particles.Comment: 10 pages, 12 figures, accepted for publication in A&A (27/11/2015) - abstract edited because of limited character

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