P-Match: transcription factor binding site search by combining patterns and weight matrices

P-Match is a new tool for identifying transcription factor (TF) binding sites in DNA sequences. It combines pattern matching and weight matrix approaches thus providing higher accuracy of recognition than each of the methods alone. P-Match is closely interconnected with the TRANSFAC(®) database. In particular, P-Match uses the matrix library as well as sets of aligned known TF-binding sites collected in TRANSFAC(®) and therefore provides the possibility to search for a large variety of different TF binding sites. Using results of extensive tests of recognition accuracy, we selected three sets of optimized cut-off values that minimize either false negatives or false positives, or the sum of both errors. Comparison with the weight matrix approaches such as Match™ tool shows that P-Match generally provides superior recognition accuracy in the area of low false negative errors (high sensitivity). As familiar to the user of Match™, P-Match also allows to save user-specific profiles that include selected subsets of matrices with corresponding TF-binding sites or user-defined cut-off values. Furthermore, a number of tissue-specific profiles are provided that were compiled by the TRANSFAC(®) team. A public version of the P-Match tool is available at

Modelling the supernova-driven ISM in different environments

We use hydrodynamical simulations in a (256 pc)3 periodic box to model the impact of supernova (SN) explosions on the multiphase interstellar medium (ISM) for initial densities n=0.5-30cm−3 and SN rates 1-720Myr−1. We include radiative cooling, diffuse heating, and the formation of molecular gas using a chemical network. The SNe explode either at random positions, at density peaks, or both. We further present a model combining thermal energy for resolved and momentum input for unresolved SNe. Random driving at high SN rates results in hot gas (T≳106K) filling >90 per cent of the volume. This gas reaches high pressures (10450 per cent), residing in small, dense clumps. Such a model might resemble the dense ISM in high-redshift galaxies. Peak driving results in huge radiative losses, producing a filamentary ISM with virtually no hot gas, and a small molecular hydrogen mass fraction (≪1 per cent). Varying the ratio of peak to random SNe yields ISM properties in between the two extremes, with a sharp transition for equal contributions. The velocity dispersion in H i remains≲10 km s−1 in all cases. For peak driving, the velocity dispersion in Hα can be as high as 70 km s−1 due to the contribution from young, embedded SN remnant

Ion acceleration from microstructured targets irradiated by high-intensity picosecond laser pulses

Structures on the front surface of thin foil targets for laser-driven ion acceleration have been proposed to increase the ion source maximum energy and conversion efficiency. While structures have been shown to significantly boost the proton acceleration from pulses of moderate-energy fluence, their performance on tightly focused and high-energy lasers remains unclear. Here, we report the results of laser-driven three-dimensional (3D)-printed microtube targets, focusing on their efficacy for ion acceleration. Using the high-contrast (∼1012) PHELIX laser (150J, 1021W/cm2), we studied the acceleration of ions from 1-μm-thick foils covered with micropillars or microtubes, which we compared with flat foils. The front-surface structures significantly increased the conversion efficiency from laser to light ions, with up to a factor of 5 higher proton number with respect to a flat target, albeit without an increase of the cutoff energy. An optimum diameter was found for the microtube targets. Our findings are supported by a systematic particle-in-cell modeling investigation of ion acceleration using 2D simulations with various structure dimensions. Simulations reproduce the experimental data with good agreement, including the observation of the optimum tube diameter, and reveal that the laser is shuttered by the plasma filling the tubes, explaining why the ion cutoff energy was not increased in this regime.Fil: Bailly Grandvaux, M.. University of California at San Diego; Estados UnidosFil: Kawahito, D.. University of California at San Diego; Estados UnidosFil: McGuffey, C.. University of California at San Diego; Estados UnidosFil: Strehlow, J.. University of California at San Diego; Estados UnidosFil: Edghill, B.. University of California at San Diego; Estados UnidosFil: Wei, M.S.. Laboratory For Laser Energetics; Estados UnidosFil: Alexander, N.. General Atomics; Estados UnidosFil: Haid, A.. General Atomics; Estados UnidosFil: Brabetz, C.. Helmholtzzentrum Für Schwerionenforschung; AlemaniaFil: Bagnoud, V.. Helmholtzzentrum Für Schwerionenforschung; AlemaniaFil: Hollinger, R.. State University of Colorado - Fort Collins; Estados UnidosFil: Capeluto, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Rocca, J.J.. State University of Colorado - Fort Collins; Estados UnidosFil: Beg, F.N.. University of California at San Diego; Estados Unido

Modelling the supernova-driven ISM in different environments

We use hydrodynamical simulations in a $(256\;{\rm pc})^3$ periodic box to model the impact of supernova (SN) explosions on the multi-phase interstellar medium (ISM) for initial densities $n = 0.5-30$ cm$^{-3}$ and SN rates $1-720$ Myr$^{-1}$. We include radiative cooling, diffuse heating, and the formation of molecular gas using a chemical network. The SNe explode either at random positions, at density peaks, or both. We further present a model combining thermal energy for resolved and momentum input for unresolved SNe. Random driving at high SN rates results in hot gas ($T\gtrsim 10^6$ K) filling $> 90$% of the volume. This gas reaches high pressures ($10^4 < P/k_\mathrm{B} < 10^7$ K cm$^{-3}$) due to the combination of SN explosions in the hot, low density medium and confinement in the periodic box. These pressures move the gas from a two-phase equilibrium to the single-phase, cold branch of the cooling curve. The molecular hydrogen dominates the mass ($>50$%), residing in small, dense clumps. Such a model might resemble the dense ISM in high-redshift galaxies. Peak driving results in huge radiative losses, producing a filamentary ISM with virtually no hot gas, and a small molecular hydrogen mass fraction ($\ll 1$%). Varying the ratio of peak to random SNe yields ISM properties in between the two extremes, with a sharp transition for equal contributions. The velocity dispersion in HI remains $\lesssim 10$ km s$^{-1}$ in all cases. For peak driving the velocity dispersion in H$_\alpha$ can be as high as $70$ km s$^{-1}$ due to the contribution from young, embedded SN remnants.Comment: 19 pages, 12 figures, 2 tables. Accepted for publication in MNRAS. Minor revisions to match published versio

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

October 1966

Massachusetts Turf and Lawn Grass CouncilBetter Turf Through Research and Educatio

Fielding the NIF Cryogenic Ignition Target

The United States Department of Energy has embarked on a campaign to conduct credible fusion ignition experiments on the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory in 2010. The target assembly specified for this campaign requires the formation of a deuterium/tritium (DT) fuel ice layer on the inside of a 2 millimeter diameter capsule positioned at the center of a 9 millimeter long by 5 millimeter diameter cylinder, called a hohlraum. The ice layer requires micrometer level accuracy and must be formed and maintained at temperatures below 19 K. At NIF shot time, the target must be positioned at the center of the NIF 10 meter diameter target chamber, aligned to the laser beam lines and held stable to less than 7 micrometers rms. We have completed the final design and are integrating the systems necessary to create, characterize and field the cryogenic target for ignition experiments. These designs, with emphasis on the challenges of fielding a precision cryogenic positioning system will be presented

The use of oral recombinant feline interferon omega in two cats with type II diabetes mellitus and concurrent feline chronic gingivostomatitis syndrome

Articles in International JournalsFeline Chronic Gingivostomatitis Syndrome (FCGS) is a common disease in clinical practice. Among the therapeutic options available, long-acting corticosteroids are frequently used due to their anti-inflammatory and immunosuppressive properties. Although they may improve the clinical symptoms, they can lead to a progressive form of the disease that becomes refractory to treatment. Furthermore, their direct relationship with type II diabetes mellitus (DM) is well known. Consequently, these drugs are controversial and not recommended for routine management of FCGS. Recombinant feline interferon-omega (rFeIFN-ω) is an immunomodulatory compound. Recently, its daily oral administration has been shown to be successful in treating refractory cases of FCGS. This case study describes two clinical cases of type II DM complicated by FCGS. Both animals were calicivirus positive and they had been previously treated with long-acting corticosteroids, which may have been the major cause of DM. The two cats were treated with glargine insulin (Lantus, starting dose 1 IU/cat twice daily (BID)), achieving remission 10 and 18 weeks later respectively. Considering the difficulty with control of FCGS in these animals, an oral daily dose of rFeIFN-ω was started as an alternative to long-acting corticosteroids. In both cats oral clinical signs gradually improved and 60 days after the start of therapy the owners reported a significant relief of pain during mastication. According to the authors’ knowledge, this is the first case report that describes the successful use of rFeIFN-ω in the management of FCGS in type II diabetic cats, in which long-acting corticosteroids are contraindicated