Effects of dexamethasone on TNF-alpha-induced release of cytokines from purified human blood eosinophils

BACKGROUND: TNF-alpha is an important mediator in allergy also for its effects on eosinophils. METHODS: The effect of dexamethasone on TNF-alpha induced eosinophils survival, degranulation (ECP), cytokines release (IL-8, GM-CSF) and adhesion to VCAM-1, ICAM-1 and IgG coated wells (EPO release) were evaluated. RESULTS: The drug inhibited IL-8 and GM-CSF production, but not viability, degranulation or adhesion in human peripheral blood eosinophils. CONCLUSION: These results indicate that part of the activity of glucocorticosteroids on eosinophils may be mediated by their ability to inhibit cytokine secretion that in turn is important for the perpetuation of the allergic inflammation

Five New Millisecond Pulsars From a Radio Survey of 14 Unidentified Fermi-LAT Gamma-ray Sources

We have discovered five millisecond pulsars (MSPs) in a survey of 14 unidentified Fermi-LAT sources in the southern sky using the Parkes radio telescope. PSRs J0101-6422, J1514-4946, and J1902-5105 reside in binaries, while PSRs J1658-5324 and J1747-4036 are isolated. Using an ephemeris derived from timing observations of PSR J0101-6422 (P =2.57 ms, DM=12 pc cm-3), we have detected {\gamma}-ray pulsations and measured its proper motion. Its {\gamma}-ray spectrum (a power law of {\Gamma} = 0.9 with a cutoff at 1.6 GeV) and efficiency are typical of other MSPs, but its radio and {\gamma}-ray light curves challenge simple geometric models of emission. The high success rate of this survey-enabled by selecting {\gamma}-ray sources based on their detailed spectral characteristics-and other similarly successful searches indicate that a substantial fraction of the local population of MSPs may soon be known.Comment: 6 pages, 3 figures, 2 tables, accepted by ApJ

Radio Detection of the Fermi LAT Blind Search Millisecond Pulsar J1311-3430

We report the detection of radio emission from PSR J1311-3430, the first millisecond pulsar discovered in a blind search of Fermi Large Area Telescope (LAT) gamma-ray data. We detected radio pulsations at 2 GHz, visible for <10% of ~4.5-hrs of observations using the Green Bank Telescope (GBT). Observations at 5 GHz with the GBT and at several lower frequencies with Parkes, Nancay, and the Giant Metrewave Radio Telescope resulted in non-detections. We also report the faint detection of a steep spectrum continuum radio source (0.1 mJy at 5 GHz) in interferometric imaging observations with the Jansky Very Large Array. These detections demonstrate that PSR J1311-3430, is not radio quiet and provides additional evidence that the radio beaming fraction of millisecond pulsars is very large. The radio detection yields a distance estimate of 1.4 kpc for the system, yielding a gamma-ray efficiency of 30%, typical of LAT-detected MSPs. We see apparent excess delay in the radio pulsar as the pulsar appears from eclipse and we speculate on possible mechanisms for the non-detections of the pulse at other orbital phases and observing frequencies.Comment: 6 pages, 4 figures. ApJ Letters, in pres

The High Time Resolution Universe Survey VI: An Artificial Neural Network and Timing of 75 Pulsars

We present 75 pulsars discovered in the mid-latitude portion of the High Time Resolution Universe survey, 54 of which have full timing solutions. All the pulsars have spin periods greater than 100 ms, and none of those with timing solutions are in binaries. Two display particularly interesting behaviour; PSR J1054-5944 is found to be an intermittent pulsar, and PSR J1809-0119 has glitched twice since its discovery. In the second half of the paper we discuss the development and application of an artificial neural network in the data-processing pipeline for the survey. We discuss the tests that were used to generate scores and find that our neural network was able to reject over 99% of the candidates produced in the data processing, and able to blindly detect 85% of pulsars. We suggest that improvements to the accuracy should be possible if further care is taken when training an artificial neural network; for example ensuring that a representative sample of the pulsar population is used during the training process, or the use of different artificial neural networks for the detection of different types of pulsars.Comment: 15 pages, 8 figure

PSR J2030+3641: radio discovery and gamma-ray study of a middle-aged pulsar in the now identified Fermi-LAT source 1FGL J2030.0+3641

In a radio search with the Green Bank Telescope of three unidentified low Galactic latitude Fermi-LAT sources, we have discovered the middle-aged pulsar J2030+3641, associated with 1FGL J2030.0+3641 (2FGL J2030.0+3640). Following the detection of gamma-ray pulsations using a radio ephemeris, we have obtained a phase-coherent timing solution based on gamma-ray and radio pulse arrival times that spans the entire Fermi mission. With a rotation period of 0.2 s, spin-down luminosity of 3e34 erg/s, and characteristic age of 0.5 Myr, PSR J2030+3641 is a middle-aged neutron star with spin parameters similar to those of the exceedingly gamma-ray-bright and radio-undetected Geminga. Its gamma-ray flux is 1% that of Geminga, primarily because of its much larger distance, as suggested by the large integrated column density of free electrons, DM=246 pc/cc. We fit the gamma-ray light curve, along with limited radio polarimetric constraints, to four geometrical models of magnetospheric emission, and while none of the fits have high significance some are encouraging and suggest that further refinements of these models may be worthwhile. We argue that not many more non-millisecond radio pulsars may be detected along the Galactic plane that are responsible for LAT sources, but that modified methods to search for gamma-ray pulsations should be productive -- PSR J2030+3641 would have been found blindly in gamma rays if only >0.8 GeV photons had been considered, owing to its relatively flat spectrum and location in a region of high soft background.Comment: Accepted for publication in ApJ, 9 pages, 6 figure

Preclinical development of a bispecific TNFα/IL-23 neutralising domain antibody as a novel oral treatment for inflammatory bowel disease.

Anti-TNFα and anti-IL-23 antibodies are highly effective therapies for Crohn's disease or ulcerative colitis in a proportion of patients. V56B2 is a novel bispecific domain antibody in which a llama-derived IL-23p19-specific domain antibody, humanised and engineered for intestinal protease resistance, V900, was combined with a previously-described TNFα-specific domain antibody, V565. V56B2 contains a central protease-labile linker to create a single molecule for oral administration. Incubation of V56B2 with trypsin or human faecal supernatant resulted in a complete separation of the V565 and V900 monomers without loss of neutralising potency. Following oral administration of V900 and V565 in mice, high levels of each domain antibody were detected in the faeces, demonstrating stability in the intestinal milieu. In ex vivo cultures of colonic biopsies from IBD patients, treatment with V565 or V900 inhibited tissue phosphoprotein levels and with a combination of the two, inhibition was even greater. These results support further development of V56B2 as an oral therapy for IBD with improved safety and efficacy in a greater proportion of patients as well as greater convenience for patients compared with traditional monoclonal antibody therapies

Invasive Pneumococcal Pneumonia and Respiratory Virus Co-infections

Each year, especially in the winter, many get sick and some die of invasive pneumococcal pneumonia. Does this type of pneumonia increase in the winter because people are in closer contact indoors?  Or are people more susceptible to this bacterial disease after having had a seasonal respiratory virus infection?  A season-by-season analysis found an association between pneumococcal pneumonia and two viruses (influenza and respiratory syncytial virus). The association varied by season and was strongest when the predominant influenza virus subtype was H3N2. Vaccination against influenza and RSV should also help protect against pneumococcal pneumonia

Eight gamma-ray pulsars discovered in blind frequency searches of Fermi LAT data

We report the discovery of eight gamma-ray pulsars in blind frequency searches using the LAT, onboard the Fermi Gamma-ray Space Telescope. Five of the eight pulsars are young (tau_c10^36 erg/s), and located within the Galactic plane (|b|<3 deg). The remaining three are older, less energetic, and located off the plane. Five pulsars are associated with sources included in the LAT bright gamma-ray source list, but only one, PSR J1413-6205, is clearly associated with an EGRET source. PSR J1023-5746 has the smallest characteristic age (tau_c=4.6 kyr) and is the most energetic (Edot=1.1E37 erg/s) of all gamma-ray pulsars discovered so far in blind searches. PSRs J1957+5033 and J2055+25 have the largest characteristic ages (tau_c~1 Myr) and are the least energetic (Edot~5E33 erg/s) of the newly-discovered pulsars. We present the timing models, light curves, and detailed spectral parameters of the new pulsars. We used recent XMM observations to identify the counterpart of PSR J2055+25 as XMMU J205549.4+253959. In addition, publicly available archival Chandra X-ray data allowed us to identify the likely counterpart of PSR J1023-5746 as a faint, highly absorbed source, CXOU J102302.8-574606. The large X-ray absorption indicates that this could be among the most distant gamma-ray pulsars detected so far. PSR J1023-5746 is positionally coincident with the TeV source HESS J1023-575, located near the young stellar cluster Westerlund 2, while PSR J1954+2836 is coincident with a 4.3 sigma excess reported by Milagro at a median energy of 35 TeV. Deep radio follow-up observations of the eight pulsars resulted in no detections of pulsations and upper limits comparable to the faintest known radio pulsars, indicating that these can be included among the growing population of radio-quiet pulsars in our Galaxy being uncovered by the LAT, and currently numbering more than 20.Comment: Submitted to Ap