The Pla surface protease/adhesin of Yersinia pestis mediates bacterial invasion into human endothelial cells

AbstractThe plasminogen activator Pla of Yersinia pestis belongs to the omptin family of enterobacterial surface proteases and is responsible for the highly efficient invasion of the plague bacterium from the subcutaneous infection site into the circulation. Y. pestis has been reported to invade human epithelial cells. Here, we investigated the role of Pla in bacterial invasion into human endothelial cells. Expression of Pla in recombinant Escherichia coli XL1(pMRK1) enhanced bacterial invasion into ECV304 cells. The invasiveness was not affected by substitution mutation at the residues S99 or D206 that are needed for the proteolytic activity of Pla. Pla-expressing bacteria adhered to the extracellular matrix of ECV304 cells. Only weak adhesion and poor invasion were seen with the recombinant E. coli XL1(pMRK2), which expresses the omptin homolog from E. coli. The results identify Pla as an invasion protein of Y. pestis and show that the invasive function does not involve the proteolytic activity of Pla

Multifrequency VLBA Monitoring of 3C 273 during the INTEGRAL Campaign in 2003 - I. Kinematics of the Parsec Scale Jet from 43 GHz Data

In this first of a series of papers describing polarimetric multifrequency Very Long Baseline Array (VLBA) monitoring of 3C 273 during a simultaneous campaign with the INTEGRAL gamma-ray satellite in 2003, we present 5 Stokes I images and source models at 7 mm. We show that a part of the inner jet (1-2 milliarcseconds from the core) is resolved in a direction transverse to the flow, and we analyse the kinematics of the jet within the first 10 mas. Based on the VLBA data and simultaneous single-dish flux density monitoring, we determine an accurate value for the Doppler factor of the parsec scale jet, and using this value with observed proper motions, we calculate the Lorentz factors and the viewing angles for the emission components in the jet. Our data indicates a significant velocity gradient across the jet with the components travelling near the southern edge being faster than the components with more northern path. We discuss our observations in the light of jet precession model and growing plasma instabilities.Comment: Accepted for publication in Astronomy & Astrophysics, 16 pages, 15 figure

INTEGRAL observations of the blazar Mrk 421 in outburst (Results of a multi-wavelength campaign)

We report the results of a multi-wavelength campaign on the blazar Mrk 421 during outburst. We observed four strong flares at X-ray energies that were not seen at other wavelengths (partially because of missing data). From the fastest rise in the X-rays, an upper limit could be derived on the extension of the emission region. A time lag between high-energy and low-energy X-rays was observed, which allowed an estimation of the magnetic-field strength. The spectral analysis of the X-rays revealed a slight spectral hardening of the low-energy (3 - 43 keV) spectral index. The hardness-ratio analysis of the Swift-XRT (0.2 - 10 keV) data indicated a small correlation with the intensity; i. e., a hard-to-soft evolution was observed. At the energies of IBIS/ISGRI (20 - 150 keV), such correlations are less obvious. A multiwavelength spectrum was composed and the X-ray and bolometric luminosities are calculated.Comment: 15 pages, 18 figures; accepted by Astronomy & Astrophysic

Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A : A nationwide real-world study with 700 person-years

AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.Peer reviewe

37 GHz observations of a large sample of BL Lacertae objects

We present 37 GHz data obtained at Metsahovi Radio Observatory in 2001 December - 2005 April for a large sample of BL Lacertae objects. We also report the mean variability indices and radio spectral indices in frequency intervals 5 - 37 GHz and 37 - 90 GHz. Approximately 34 % of the sample was detected at 37 GHz, 136 BL Lacertae objects in all. A large majority of the detected sources were low-energy BL Lacs (LBLs). The variability index values of the sample were diverse, the mean fractional variability of the sample being \Delta S_2 = 0.31. The spectral indices also varied widely, but the average radio spectrum of the sample sources is flat. Our observations show that many of the high-energy BL Lacs (HBL), which are usually considered radio-quiet, can at times be detected at 37 GHz.Comment: 12 pages, 5 figures + 5 tables. Published in Astronomical Journa

VLBI and Single Dish Monitoring of 3C84 in the Period of 2009-2011

The radio galaxy 3C 84 is a representative of gamma-ray-bright misaligned active galactic nuclei (AGNs) and one of the best laboratories to study the radio properties of the sub-pc jet in connection with the gamma-ray emission. In order to identify possible radio counterparts of the gamma-ray emissions in 3C 84, we study the change in structure within the central 1 pc and the light curve of sub-pc-size components C1, C2, and C3. We search for any correlation between changes in the radio components and the gamma-ray flares by making use of VLBI and single dish data. Throughout the radio monitoring spanning over two GeV gamma-ray flares detected by the {\it Fermi}-LAT and the MAGIC Cherenkov Telescope in the periods of 2009 April to May and 2010 June to August, total flux density in radio band increases on average. This flux increase mostly originates in C3. Although the gamma-ray flares span on the timescale of days to weeks, no clear correlation with the radio light curve on this timescale is found. Any new prominent components and change in morphology associated with the gamma-ray flares are not found on the VLBI images.Comment: 6 pages, 3 figures, accepted for publication in MNRAS lette

Can processes make relationships work? The Triple Helix between structure and action

This contribution seeks to explore how complex adaptive theory can be applied at the conceptual level to unpack Triple Helix models. We use two cases to examine this issue – the Finnish Strategic Centres for Science, Technology & Innovation (SHOKs) and the Canadian Business-led Networks of Centres of Excellence (BL-NCE). Both types of centres are organisational structures that aspire to be business-led, with a considerable portion of their activities driven by (industrial) users’ interests and requirements. Reflecting on the centres’ activities along three dimensions – knowledge generation, consensus building and innovation – we contend that conceptualising the Triple Helix from a process perspective will improve the dialogue between stakeholders and shareholders

Locating the γ-ray emission site in Fermi/LAT blazars – II. Multifrequency correlations

In an attempt to constrain and understand the emission mechanism of γ-rays, we perform a cross-correlation analysis of 15 blazars using light curves in millimetre, optical and γ-rays. We use discrete correlation function and consider only correlations significant at the 99 per cent level. A strong correlation was found between 37 and 95 GHz with a near-zero time delay in most of the sources, and ∼1 month or longer in the rest. A similar result was obtained between the optical and γ-ray bands. Of the 15 sources, less than 50 per cent showed a strong correlation between the millimetre and γ-ray or millimetre and optical bands. The primary reason for the lack of statistically significant correlation is the absence of a major outburst in the millimetre bands of most of the sources during the 2.5 yr time period investigated in our study. This may indicate that only the long-term variations or large flares are correlated between these bands. The variability of the sources at every waveband was also inspected using fractional rms variability (F_(var)). The F_(var) displays an increase with frequency reaching its maximum in the γ-rays