Cellular expression and crystal structure of the murine cytomegalovirus MHC-Iv glycoprotein, m153

Mouse cytomegalovirus (MCMV), a β-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. MCMV encodes the m145 family of putative immunoevasins with predicted MHC-I structure. Functions attributed to some family members include downregulation of host MHC-I (m152) and NKG2D ligands (m145, m152, m155) and interaction with inhibitory or activating NK receptors (m157). We present the cellular, biochemical and structural characterization of m153, which is a heavily glycosylated homodimer, that does not require β2m or peptide, and is expressed at the surface of MCMV-infected cells. Its 2.4 Å crystal structure confirms that this compact molecule preserves an MHC-I-like fold and reveals a novel mode of dimerization, confirmed by site-directed mutagenesis, and a distinctive disulfide-stabilized extended amino terminus. The structure provides a useful framework for comparative analysis of the divergent members of the m145 family

Palaeoenvironmental and Archaeological Implications of a Sediment Core from Polje Čepić, Istria, Croatia

Palaeoenvironmental and archaeological records provide an invaluable framework for land and water management in karstic areas of the Mediterranean realm. We present the results from analyses carried out on three segments of a sediment core extracted in 2004 from a portion of Polje Čepić (Istria, Croatia), a tectono-karstic depression covered in water until artificial drainage took place in 1932. We used bulk sediment analyses, pollen analysis and radiocarbon dating to assess the possible contribution of people to the progressive siltation of the lake, and compared our results with recent archaeological discoveries made on the polje margins. The dating of the sequence points to the presence of a predominantly wet landscape at the coring location since at least 7000 years cal BP. The coincidence of cereal type pollen grains with several open-air archaeological sites indicates that small scale agricultural practices possibly developed around the polje in Neolithic times, ca 6500 years cal BP. Concentrations of charcoal in the sediment core at this time suggest the use of fire clearance as part of the agricultural practice. During the Bronze and Iron Ages, the possible intensification of forest clearance and agricultural practices is indicated by: (1) an increase in the number and type of archaeological sites found around the polje; (2) a more open plant landscape in the upper part of the analysed sequence; and (3) a three-fold increase in the sedimentation rate, possibly starting as early as 4000 years cal BP. Wetter climate conditions and higher erosion of the surrounding slopes probably led to the progressive siltation of the lake. Finally, in 1932 the lake was artificially drained and Istria lost its largest natural basin of fresh water

Data compression for the First G-APD Cherenkov Telescope

The First Geiger-mode Avalanche photodiode (G-APD) Cherenkov Telescope (FACT) has been operating on the Canary island of La Palma since October 2011. Operations were automated so that the system can be operated remotely. Manual interaction is required only when the observation schedule is modified due to weather conditions or in case of unexpected events such as a mechanical failure. Automatic operations enabled high data taking efficiency, which resulted in up to two terabytes of FITS files being recorded nightly and transferred from La Palma to the FACT archive at ISDC in Switzerland. Since long term storage of hundreds of terabytes of observations data is costly, data compression is mandatory. This paper discusses the design choices that were made to increase the compression ratio and speed of writing of the data with respect to existing compression algorithms. Following a more detailed motivation, the FACT compression algorithm along with the associated I/O layer is discussed. Eventually, the performances of the algorithm is compared to other approaches.Comment: 17 pages, accepted to Astronomy and Computing special issue on astronomical file format

FACT - Monitoring Blazars at Very High Energies

The First G-APD Cherenkov Telescope (FACT) was built on the Canary Island of La Palma in October 2011 as a proof of principle for silicon based photosensors in Cherenkov Astronomy. The scientific goal of the project is to study the variability of active galatic nuclei (AGN) at TeV energies. Observing a small sample of TeV blazars whenever possible, an unbiased data sample is collected. This allows to study the variability of the selected objects on timescales from hours to years. Results from the first three years of monitoring will be presented. To provide quick flare alerts to the community and trigger multi-wavelength observations, a quick look analysis has been installed on-site providing results publicly online within the same night. In summer 2014, several flare alerts were issued. Results of the quick look analysis are summarized.Comment: 2014 Fermi Symposium proceedings - eConf C14102.

VLBI imaging of a flare in the Crab Nebula: More than just a spot

We report on very long baseline interferometry (VLBI) observations of the radio emission from the inner region of the Crab Nebula, made at 1.6 GHz and 5 GHz after a recent high-energy flare in this object. The 5 GHz data have provided only upper limits of 0.4 milli-Jansky (mJy) on the flux density of the pulsar and 0.4 mJy/beam on the brightness of the putative flaring region. The 1.6 GHz data have enabled imaging the inner regions of the nebula on scales of up to ~40". The emission from the inner "wisps" is detected for the first time with VLBI observations. A likely radio counterpart (designated "C1") of the putative flaring region observed with Chandra and HST is detected in the radio image, with an estimated flux density of $0.5\pm 0.3$\,mJy and a size of 0.2-0.6". Another compact feature ("C2") is also detected in the VLBI image closer to the pulsar, with an estimated flux density of 0.4 +- 0.2 mJy and a size smaller than 0{\farcs}2. Combined with the broad-band SED of the flare, the radio properties of C1 yield a lower limit of ~0.5 mG for the magnetic field and a total minimum energy of 1.2*10^41 ergs vested in the flare (corresponding to using about 0.2% of the pulsar spin-down power). The 1.6 GHz observations provide upper limits for the brightness (0.2 mJy/beam) and total flux density (0.4 mJy) of the optical Knot 1 located at 0.6" from the pulsar. The absolute position of the Crab pulsar is determined, and an estimate of the pulsar proper motion is obtained.Comment: Astronomy & Astrophysics; accepted; 10 pages, 8 figure

Mirror Position Determination for the Alignment of Cherenkov Telescopes

Imaging Atmospheric Cherenkov Telescopes (IACTs) need imaging optics with large apertures to map the faint Cherenkov light emitted in extensive air showers onto their image sensors. Segmented reflectors fulfill these needs using mass produced and light weight mirror facets. However, as the overall image is the sum of the individual mirror facet images, alignment is important. Here we present a method to determine the mirror facet positions on a segmented reflector in a very direct way. Our method reconstructs the mirror facet positions from photographs and a laser distance meter measurement which goes from the center of the image sensor plane to the center of each mirror facet. We use our method to both align the mirror facet positions and to feed the measured positions into our IACT simulation. We demonstrate our implementation on the 4 m First Geiger-mode Avalanche Cherenkov Telescope (FACT).Comment: 11 figures, small ray tracing performance simulation, and implementation demonstratio

Investigation of β-carotene–gelatin composite particles with a multiwavelength UV/vis detector for the analytical ultracentrifuge

A multiwavelength UV/vis detector for the analytical ultracentrifuge (MWL-AUC) has been developed recently. In this work, β-carotene–gelatin composite particles are investigated with MWL-AUC. Band centrifugation with a Vinograd cell is used to ensure maximum sample separation. Spectral changes of the system are observed in dependence of the sedimentation coefficient and are attributed to a previously unknown inhomogeneity of the β-carotene chemical composition with both H- and J-aggregates coexisting in a mixture. In addition, our data suggest that pure H- and J-aggregates exist in a particle while their relative concentrations in a mixture determine the color characteristics of the sample. The unique abilities and properties of MWL-AUC include sedimentation coefficient distributions for all possible wavelengths, full UV/vis spectra of each different species in the mixture and 3D movies of the sedimentation process. These properties significantly extend the scope of the analytical ultracentrifuge technique and show that complex biopolymer multicomponent mixtures can be resolved into their individual species

Load-sharing policies in parallel simulation of agent-based demographic models

Execution parallelism in agent-Based Simulation (ABS) allows to deal with complex/large-scale models. This raises the need for runtime environments able to fully exploit hardware parallelism, while jointly offering ABS-suited programming abstractions. In this paper, we target last-generation Parallel Discrete Event Simulation (PDES) platforms for multicore systems. We discuss a programming model to support both implicit (in-place access) and explicit (message passing) interactions across concurrent Logical Processes (LPs). We discuss different load-sharing policies combining event rate and implicit/explicit LPs’ interactions. We present a performance study conducted on a synthetic test case, representative of a class of agent-based models.Peer ReviewedPostprint (author's final draft

Lecithin : cholesterol acyltransferase: symposium on 50 years of biomedical research from its discovery to latest findings

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. This report is a summary from a 2017 symposium where Dr. Norum recounted the history of FLD and leading experts on LCAT shared their results. The Tesmer laboratory shared structural findings on LCAT and the close homolog, lysosomal phospholipase A2. Results from studies of FLD patients in Finland, Brazil, Norway, and Italy were presented, as well as the status of a patient registry. Drs. Kuivenhoven and Calabresi presented data from carriers of genetic mutations suggesting that FLD does not necessarily accelerate atherosclerosis. Dr. Ng shared that LCAT-null mice were protected from diet-induced obesity, insulin resistance, and nonalcoholic fatty liver disease. Dr. Zhou presented multiple innovations for increasing LCAT activity for therapeutic purposes, whereas Dr. Remaley showed results from treatment of an FLD patient with recombinant human LCAT (rhLCAT). Dr. Karathanasis showed that rhLCAT infusion in mice stimulates cholesterol efflux and suggested that it could also enhance cholesterol efflux from macrophages. While the role of LCAT in atherosclerosis remains elusive, the consensus is that a continued study of both the enzyme and disease will lead toward better treatments for patients with heart disease and FLD.Peer reviewe