Respiratory syncytial virus infection reduces lung inflammation and fibrosis in mice exposed to vanadium pentoxide

<p>Abstract</p> <p>Background</p> <p>Vanadium pentoxide (V₂O₅) exposure is a cause of occupational bronchitis and airway fibrosis. Respiratory syncytial virus (RSV) is a ubiquitous pathogen that causes airway inflammation. It is unknown whether individuals with pre-existing respiratory viral infection are susceptible to V₂O₅-induced bronchitis. We hypothesized that respiratory viral infection will exacerbate vanadium-induced lung fibrosis.</p> <p>Methods</p> <p>In this study we investigated the effect of RSV pre- or post-exposure to V₂O₅in male AKR mice. Mice were pre-exposed by intranasal aspiration to RSV or media vehicle prior to intranasal aspiration of V₂O₅or saline vehicle at day 1 or day 7. A parallel group of mice were treated first with V₂O₅or saline vehicle at day 1 and day 7 then post-exposed to RSV or media vehicle at day 8.</p> <p>Results</p> <p>V₂O₅-induced airway inflammation and fibrosis were decreased by RSV pre- or post-exposure. Real time quantitative RT-PCR showed that V₂O₅significantly increased lung mRNAs encoding pro-fibrogenic growth factors (TGF-β1, CTGF, PDGF-C) and collagen (Col1A2), but also increased mRNAs encoding anti-fibrogenic type I interferons (IFN-α, -β) and IFN-inducible chemokines (CXCL9 and CXCL10). RSV pre- or post-exposure caused a significantly reduced mRNAs of pro-fibrogenic growth factors and collagen, yet reduced RNA levels of anti-fibrogenic interferons and CXC chemokines.</p> <p>Conclusions</p> <p>Collectively these data suggest that RSV infection reduces the severity of V₂O₅-induced fibrosis by suppressing growth factors and collagen genes. However, RSV suppression of V₂O₅-induced IFNs and IFN-inducible chemokines suggests that viral infection also suppresses the innate immune response that normally serves to resolve V₂O₅-induced fibrosis.</p

A variability analysis of low-latitude unidentified gamma-ray sources

We present a study of 40 low-latitude unidentified 3EG gamma-ray sources which were found to be not positionally coincident with any known class of potential gamma-ray emitters in the Galaxy (Romero, Benaglia & Torres, 1999). We have performed a variability analysis which reveals that many of these 40 sources are variable. These sources have, in addition, a steep mean value of the gamma-ray spectral index, $= 2.41 \pm 0.2$, which, combined with the high level of variability seems to rule out a pulsar origin. The positional coincidences with uncatalogued candidates to supernova remnants were also studied. Only 7 sources in the sample are spatially coincident with these candidates, a result that is shown to be consistent with the expected level of pure chance association. A complementary search for weak radio counterparts was also conducted and the results are presented as an extensive table containing all significant point-like radio sources within the 40 EGRET fields. We argue that in order to produce the high variability, steep gamma-ray spectra, and absence of strong radio counterparts observed in some of the gamma-ray sources of our sample a new class of objects should be postulated, and we analyze a viable candidate.Comment: Paper updated to match the accepted version to appear in Astronomy and Astrophysics, 2001. Tables 5,6,7 and 8 are in ascii format and need to be printed separately. they can also be obtained from http://www.iar.unlp.edu.ar/garra Table 5 is 62 pages long. Download the source to obtain the table

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Habitable Zones in the Universe

Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review the historical development of the concept of habitable zones and the present state of the research. We also suggest ways to make progress on each of the habitable zones and to unify them into a single concept encompassing the entire universe.Comment: 71 pages, 3 figures, 1 table; to be published in Origins of Life and Evolution of Biospheres; table slightly revise

Characterization of lymphocyte populations in nonspecific interstitial pneumonia*

STUDY OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. DESIGN: Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. RESULTS: In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. CONCLUSION: The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP

Automated time activity classification based on global positioning system (GPS) tracking data

<p>Abstract</p> <p>Background</p> <p>Air pollution epidemiological studies are increasingly using global positioning system (GPS) to collect time-location data because they offer continuous tracking, high temporal resolution, and minimum reporting burden for participants. However, substantial uncertainties in the processing and classifying of raw GPS data create challenges for reliably characterizing time activity patterns. We developed and evaluated models to classify people's major time activity patterns from continuous GPS tracking data.</p> <p>Methods</p> <p>We developed and evaluated two automated models to classify major time activity patterns (i.e., indoor, outdoor static, outdoor walking, and in-vehicle travel) based on GPS time activity data collected under free living conditions for 47 participants (N = 131 person-days) from the Harbor Communities Time Location Study (HCTLS) in 2008 and supplemental GPS data collected from three UC-Irvine research staff (N = 21 person-days) in 2010. Time activity patterns used for model development were manually classified by research staff using information from participant GPS recordings, activity logs, and follow-up interviews. We evaluated two models: (a) a rule-based model that developed user-defined rules based on time, speed, and spatial location, and (b) a random forest decision tree model.</p> <p>Results</p> <p>Indoor, outdoor static, outdoor walking and in-vehicle travel activities accounted for 82.7%, 6.1%, 3.2% and 7.2% of manually-classified time activities in the HCTLS dataset, respectively. The rule-based model classified indoor and in-vehicle travel periods reasonably well (Indoor: sensitivity > 91%, specificity > 80%, and precision > 96%; in-vehicle travel: sensitivity > 71%, specificity > 99%, and precision > 88%), but the performance was moderate for outdoor static and outdoor walking predictions. No striking differences in performance were observed between the rule-based and the random forest models. The random forest model was fast and easy to execute, but was likely less robust than the rule-based model under the condition of biased or poor quality training data.</p> <p>Conclusions</p> <p>Our models can successfully identify indoor and in-vehicle travel points from the raw GPS data, but challenges remain in developing models to distinguish outdoor static points and walking. Accurate training data are essential in developing reliable models in classifying time-activity patterns.</p

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi