Multiple-View Tracing for Haskell: a New Hat

Different tracing systems for Haskell give different views of a program at work. In practice, several views are complementary and can productively be used together. Until now each system has generated its own trace, containing only the information needed for its particular view. Here we present the design of a trace that can serve several views. The trace is generated and written to file as the computation proceeds. We have implemented both the generation of the trace and several different viewers

Galectin-3 interacts with components of the nuclear ribonucleoprotein complex

Differentially spliced mRNAs following galectin‐3 depletion. (PDF 122 kb

Die Rolle der DNA-Bindungskooperativität für die p53-vermittelte Tumorsuppression im Lungentumor-Xenograft-Modell

p53 wird wegen seiner herausragenden Rolle als Tumorsuppressor auch als Wächter des Genoms bezeichnet: als Transkriptionsfaktor reguliert es die Expression zahlreicher Gene und nimmt hierdurch Einfluss auf die Zellproliferation. Bei zellulärem Stress, wie zum Beispiel bei DNA-Schädigung oder Aktivierung von Onkogenen, steigt der Spiegel von p53 in der Zelle rasch an. Mögliche Konsequenzen sind ein transienter Zellzyklusarrest, der eine DNAReparatur ermöglicht, die Seneszenz, ein irreversibler Zellzyklusarrest, oder die Apoptose, der programmierte Zelltod. Durch diese Maÿnahmen wird die Proliferation der Zelle vorerst gestoppt und der Organismus vor Generierung und Vermehrung von Krebszellen geschützt. Wie genau die Entscheidung zwischen transientem Zellzyklusarrest, Seneszenz und Apoptose getroffen wird, ist bis heute nicht abschließend geklärt. p53 bindet als Tetramer kooperativ an die DNA, was bedeutet, dass die Bindung des kompletten p53-Tetramers an die DNA stärker ist als die Summe der Bindungen der vier einzelnen p53-Monomere. Die Stabilität der Bindung zwischen den einzelnen p53-Molekülen beeinflusst die Auswahl der Target-Gene entscheidend und korreliert mit dem Ausmaÿ der induzierten Apoptose. Um den Einfluss der DNA-Bindungskooperativität von p53 auf die Tumorsuppression zu untersuchen, wurden in dieser Arbeit unterschiedlich stark kooperative p53-Mutanten stabil in eine p53-negative Lungenkarzinomzelllinie transfiziert. Im Lungentumor-Xenograft-Modell konnte gezeigt werden, dass sich bei höherer DNA-Bindungskooperativität von p53 signifikant weniger Tumore entwickeln. Eine zusätzliche Chemotherapie mit Doxorubicin vermochte die Tumormasse nochmals zu reduzieren. Diese Ergebnisse belegen eindrucksvoll die Abhängigkeit der Tumorsuppression sowie der Chemosensibilität von der DNA-Bindungskooperativität von p53. Interessanterweise war keine konstitutive Aktivität von p53 notwendig, sondern eine konditionelle Aktivierung ausschlieÿlich in der letzten Behandlungswoche führte zu einem gleichwertigen tumorsuppressiven Effekt. Dieses Wissen um die Effekte der DNA-Bindungskooperativität ist therapeutisch hoch interessant, da Substanzen, die die Kooperativität erhöhen und somit die Apoptoserate steigern, zur Behandlung von Tumorerkrankungen eingesetzt werden könnten. Alternativ könnte eine transiente Absenkung der Kooperativit ät der gesunden Körperzellen bei Chemotherapie die Nebenwirkungsrate senken

Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection

Dendritic cells can capture and transfer retroviruses in vitro across synaptic cell-cell contacts to uninfected cells, a process called trans-infection. Whether trans-infection contributes to retroviral spread in vivo remains unknown. Here, we visualize how retroviruses disseminate in secondary lymphoid tissues of living mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I-type lectin that recognizes gangliosides, captures the virus. MLV-laden macrophages then form long-lived synaptic contacts to trans-infect B-1 cells. Infected B-1 cells subsequently migrate into the lymph node to spread the infection through virological synapses. Robust infection in lymph nodes and spleen requires CD169, suggesting that a combination of fluid-based movement followed by CD169-dependent trans-infection can contribute to viral spread

Phenotype of Arabidopsis thaliana semi-dwarfs with deep roots and high growth rates under water-limiting conditions is independent of the GA5 loss-of-function alleles

BACKGROUND AND AIMS: The occurrence of Arabidopsis thaliana semi-dwarf accessions carrying inactive alleles at the gibberellin (GA) biosynthesis GA5 locus has raised the question whether there are pleiotropic effects on other traits at the root level, such as rooting depth. In addition, it is unknown whether semi-dwarfism in arabidopsis confers a growth advantage under water-limiting conditions compared with wild-type plants. The aim of this research was therefore to investigate whether semi-dwarfism has a pleiotropic effect in the root system and also whether semi-dwarfs might be more tolerant of water-limiting conditions. METHODS: The root systems of different arabidopsis semi-dwarfs and GA biosynthesis mutants were phenotyped in vitro using the GROWSCREEN-ROOT image-based software. Semi-dwarfs were phenotyped together with tall, near-related accessions. In addition, root phenotypes were investigated in soil-filled rhizotrons. Rosette growth trajectories were analysed with the GROWSCREEN-FLUORO setup based on non-invasive imaging. KEY RESULTS: Mutations in the early steps of the GA biosynthesis pathway led to a reduction in shoot as well as root size. Depending on the genetic background, mutations at the GA5 locus yielded phenotypes characterized by decreased root length in comparison with related wild-type ones. The semi-dwarf accession Pak-3 showed the deepest root system both in vitro and in soil cultivation experiments; this comparatively deep root system, however, was independent of the ga5 loss-of-function allele, as shown by co-segregation analysis. When the accessions were grown under water-limiting conditions, semi-dwarf accessions with high growth rates were identified. CONCLUSIONS: The observed diversity in root system growth and architecture occurs independently of semi-dwarf phenotypes, and is probably linked to a genetic background effect. The results show that there are no clear advantages of semi-dwarfism at low water availability in arabidopsis.International Max Planck Research School PhD Fellowship/[]/IMPRS/AlemaniaHelmholtz Association//[]//AlemaniaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro para Investigaciones en Granos y Semillas (CIGRAS

Analysis of a maximum likelihood phase estimation method for airborne multibaseline SAR interferometry

It has been shown using simulated data that phase estimation of cross-track multibaseline synthetic aperture radar (SAR) interferometric data was most efficiently achieved through a maximum likelihood (ML) method. In this paper, we apply and assess the ML approach on real data, acquired with an experimental Ka-band multibaseline system. Compared to simulated data, dealing with real data implies that several calibration steps be carried out to ensure that the data fit the model. A processing chain was, therefore, designed, including steps responsible for compensating for imperfections observed in the data, such as beam elevation angle dependent phase errors or phase errors caused by imperfect motion compensation. The performance of the ML phase estimation was evaluated by comparing it to results based on a coarse-to-fine (C2F) algorithm, where information from the shorter baselines was used only to unwrap the phase from the longest available baseline. For this purpose, flat areas with high coherence and homogeneous texture were selected in the acquired data. The results show that with only four looks, the noise level was marginally better with the C2F approach and contained fewer outliers. However, with more looks, the ML method consistently delivered better results: noise variance with the C2F approach was slightly but steadily larger than the variance obtained with ML method

Processing of MEMPHIS Ka-Band Multibaseline Interferometric SAR Data: From Raw Data to Digital Surface Models

MEMPHIS is an experimental millimeter-wave synthetic aperture radar (SAR) system that acquires cross-track multibaseline interferometric data at high resolution in a single pass, using four receive horns. In this paper, we present the SAR system and navigation data, and propose a processing chain from the raw data input to a digital surface model (DSM) output. This processing chain includes full bandwidth reconstruction of the stepped-frequency SAR data, azimuth focusing with an Extended Omega-K algorithm, generation of interferograms for each available baseline, phase unwrapping using the multibaseline data, and phase- to-height conversion. The hardware and processing chain were validated through the analysis of experimental Ka-band data. The SAR image resolution was measured with point targets and found to be    and     coarser than the theoretical value in range and azimuth, respectively. The geolocation accuracy was typically better than 0.1 m in range and 0.2 m in azimuth. Observed depression angle-dependent interferometric phase errors were successfully removed using a correction function derived from the InSAR data. Investigation of the interferometric phase noise showed the utility of a multi- baseline antenna setup; the number of looks and filter size used for the DSM generation were also derived from this analysis. The results showed that in grassland areas, the height difference between the ~2 m-resolution InSAR DSMs and the reference ALS models was 0 ±0.25 m