Pulmonary fibrosis induced by H5N1 viral infection in mice

<p>Abstract</p> <p>Background</p> <p>Inflammatory process results in lung injury that may lead to pulmonary fibrosis (PF). Here, we described PF in mice infected with H5N1 virus.</p> <p>Methods</p> <p>Eight-week-old BALB/c mice were inoculated intranasally with 1 × 10¹MID₅₀of A/Chicken/Hebei/108/2002(H5N1) viruses. Lung injury/fibrosis was evaluated by observation of hydroxyproline concentrations, lung indexes, and histopathology on days 7, 14, and 30 postinoculation.</p> <p>Results</p> <p>H5N1-inoculated mice presented two stages of pulmonary disease over a 30-d period after infection. At acute stage, infected-mice showed typical diffuse pneumonia with inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage on day 7 postinoculation. At restoration stage, most infected-mice developed PF of different severities on day 30 postinoculation, and 18% of the survived mice underwent severe interstitial and intra-alveolar fibrosis with thickened alveolar walls, collapsed alveoli and large fibrotic areas. The dramatically elevated hydroxyproline levels in H5N1-infected mice showed deposition of collagen in lungs, and confirmed fibrosis of lungs. The dry lung-to-body weight ratio was significantly increased in infected group, which might be associated with the formation of PF in H5N1-infected mice.</p> <p>Conclusion</p> <p>Our findings show that H5N1-infected mice develop the typical PF during restoration period, which will contribute to the investigation of fibrogenesis and potential therapeutic intervention in human H5N1 disease.</p

Polarimetric Multi-View Inverse Rendering

A polarization camera has great potential for 3D reconstruction since the angle of polarization (AoP) of reflected light is related to an object's surface normal. In this paper, we propose a novel 3D reconstruction method called Polarimetric Multi-View Inverse Rendering (Polarimetric MVIR) that effectively exploits geometric, photometric, and polarimetric cues extracted from input multi-view color polarization images. We first estimate camera poses and an initial 3D model by geometric reconstruction with a standard structure-from-motion and multi-view stereo pipeline. We then refine the initial model by optimizing photometric and polarimetric rendering errors using multi-view RGB and AoP images, where we propose a novel polarimetric rendering cost function that enables us to effectively constrain each estimated surface vertex's normal while considering four possible ambiguous azimuth angles revealed from the AoP measurement. Experimental results using both synthetic and real data demonstrate that our Polarimetric MVIR can reconstruct a detailed 3D shape without assuming a specific polarized reflection depending on the material.Comment: Paper accepted in ECCV 202

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

Association of Ficolin-3 with Severity and Outcome of Chronic Heart Failure

BACKGROUND: Inflammatory mechanisms involving complement activation has been shown to take part in the pathophysiology of congestive heart failure, but the initiating mechanisms are unknown. We hypothesized that the main initiator molecules of the lectin complement pathway mannose-binding lectin (MBL), ficolin-2 and ficolin-3 were related to disease severity and outcome in chronic heart failure. METHODS AND RESULTS: MBL, ficolin-2 and ficolin-3 plasma concentrations were determined in two consecutive cohorts comprising 190 patients from Hungary and 183 patients from Norway as well as controls. Disease severity and clinical parameters were determined at baseline, and all-cause mortality was registered after 5-years follow-up. In univariate analysis a low level of ficolin-3, but not that of MBL or ficolin-2, was significantly associated with advanced heart failure (New York Heart Association Class IV, p<0.001 for both cohorts) and showed inverse correlation with B- type natriuretic peptide (BNP) levels (r = -0.609, p<0.001 and r = -0.467, p<0.001, respectively). In multivariable Cox regression analysis, adjusted for age, gender and BNP, decreased plasma ficolin-3 was a significant predictor of mortality (HR 1.368, 95% CI 1.052-6.210; and HR 1.426, 95% CI 1.013-2.008, respectively). Low ficolin-3 levels were associated with increased complement activation product C3a and correspondingly decreased concentrations of complement factor C3. CONCLUSIONS: This study provides evidence for an association of low ficolin-3 levels with advanced heart failure. Concordant results from two cohorts show that low levels of ficolin-3 are associated with advanced heart failure and outcome. The decrease of ficolin-3 was associated with increased complement activation

In silico assessment of biomedical products: the conundrum of rare but not so rare events in two case studies

In silico clinical trials, defined as “The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention,” have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern. We then describe with more details two case studies, two successful applications of in silico clinical trial approaches, one relative to the University of Virginia/Padova simulator that the Food and Drug Administration has accepted as possible replacement for animal testing in the preclinical assessment of artificial pancreas technologies, and the second, an investigation of the probability of cardiac lead fracture, where a Bayesian network was used to combine in vivo and in silico observations, suggesting a whole new strategy of in silico-augmented clinical trials, to be used to increase the numerosity where recruitment is impossible, or to explore patients’ phenotypes that are unlikely to appear in the trial cohort, but are still frequent enough to be of concern

Pathogenic <i>SPTBN1</i> variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system

Updated measurement of time-dependent CP -violating observables in Bs0→J/ψ^K+^K- decays

The decay-time-dependent $CP$ asymmetry in $B^{0}_{s}\to J/\psi K^{+} K^{-}$ decays is measured using proton-proton collision data, corresponding to an integrated luminosity of $1.9\,\mathrm{fb^{-1}}$, collected with the LHCb detector at a centre-of-mass energy of $13\,\mathrm{TeV}$ in 2015 and 2016. Using a sample of approximately 117\,000 signal decays with an invariant $K^{+} K^{-}$ mass in the vicinity of the $\phi(1020)$ resonance, the $CP$-violating phase $\phi_s$ is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the $B^{0}_{s}$-$\bar{B}^{0}_{s}$ system, $\Delta\Gamma_s$. The difference of the average $B^{0}_{s}$ and $B^{0}$ meson decay widths, $\Gamma_s-\Gamma_d$, is determined using in addition a sample of $B^{0} \to J/\psi K^{+} \pi^{-}$ decays. The values obtained are $\phi_s = -0.083\pm0.041\pm0.006\,\mathrm{rad}$, $\Delta\Gamma_s = 0.077 \pm 0.008 \pm 0.003\, \mathrm{ps^{-1}}$ and $\Gamma_s-\Gamma_d = -0.0041 \pm 0.0024 \pm 0.0015\,\mathrm{ps^{-1}}$, where the first uncertainty is statistical and the second systematic. These are the most precise single measurements of these quantities to date and are consistent with expectations based on the Standard Model and with a previous LHCb analysis of this decay using data recorded at centre-of-mass energies 7 and 8 TeV. Finally, the results are combined with recent results from $B^{0}_{s}\to J/\psi \pi^{+} \pi^{-}$ decays obtained using the same dataset as this analysis, and with previous independent LHCb results

Observation of the Λb0→χc1 (3872) pK⁻ decay

Using proton-proton collision data, collected with the LHCb detector and corresponding to 1.0, 2.0 and 1.9fb$^{-1}$ of integrated luminosity at the centre-of-mass energies of 7, 8, and 13 TeV, respectively, the decay $\Lambda_b^0\to \chi_{c1}(3872)pK^-$ with $\chi_{c1}\to J/\psi\pi^+\pi^-$ is observed for the first time. The significance of the observed signal is in excess of seven standard deviations. It is found that $(58\pm15)\%$ of the decays proceed via the two-body intermediate state $\chi_{c1}(3872)\Lambda(1520)$. The~branching fraction with respect to that of the $\Lambda_b\rightarrow\psi(2S)p K^{-}$ decay mode, where the $\psi(2S)$~meson is reconstructed in the $J/\psi \pi^+\pi^-$ final state, is measured to be: \begin{equation*} \frac{\Lambda_b^0\to\chi_{c1}(3872)pK^-}{\Lambda_b\to\psi(2S)p K^-} \times \frac{\mathcal{B}(\chi_{c1} \to J/\psi \pi^+\pi^-)}{\mathcal{B}(\psi(2S)\to J/\psi \pi^+\pi^-)} = \left(5.4 \pm 1.1 \pm 0.2\right)\times 10^{-2}\,, \end{equation*} where the first uncertainty is statistical and the second is systematic