A data analysis library for gravitational wave detection

One of the main goals of Pulsar Timing Arrays (PTAs) is the direct detection of gravitational waves (GWs). A first detection will be a major leap for astronomy and substantial effort is currently going into timing as many pulsars as possible, with the highest possible accuracy. As part of the individual PTA projects, several groups are developing data analysis methods for the final stage of a gravitational-waves search pipeline: the analysis of the timing residuals. Here we report the progress of on-going work to develop, within a Bayesian framework, a comprehensive and user friendly analysis library to search for gravitational waves in PTA data

Analysis of the first IPTA Mock Data Challenge by the EPTA timing data analysis working group

This is a summary of the methods we used to analyse the first IPTA Mock Data Challenge (MDC), and the obtained results. We have used a Bayesian analysis in the time domain, accelerated using the recently developed ABC-method which consists of a form of lossy linear data compression. The TOAs were first processed with Tempo2, where the design matrix was extracted for use in a subsequent Bayesian analysis. We used different noise models to analyse the datasets: no red noise, red noise the same for all pulsars, and individual red noise per pulsar. We sampled from the likelihood with four different samplers: "emcee", "t-walk", "Metropolis-Hastings", and "pyMultiNest". All but emcee agreed on the final result, with emcee failing due to artefacts of the high-dimensionality of the problem. An interesting issue we ran into was that the prior of all the 36 (red) noise amplitudes strongly affects the results. A flat prior in the noise amplitude biases the inferred GWB amplitude, whereas a flat prior in log-amplitude seems to work well. This issue is only apparent when using a noise model with individually modelled red noise for all pulsars. Our results for the blind challenges are in good agreement with the injected values. For the GWB amplitudes we found h_c = 1.03 +/- 0.11 [10^{-14}], h_c = 5.70 +/- 0.35 [10^{-14}], and h_c = 6.91 +/- 1.72 [10^{-15}], and for the GWB spectral index we found gamma = 4.28 +/- 0.20, gamma = 4.35 +/- 0.09, and gamma = 3.75 +/- 0.40. We note that for closed challenge 3 there was quite some covariance between the signal and the red noise: if we constrain the GWB spectral index to the usual choice of gamma = 13/3, we obtain the estimates: h_c = 10.0 +/- 0.64 [10^{-15}], h_c = 56.3 +/- 2.42 [10^{-15}], and h_c = 4.83 +/- 0.50 [10^{-15}], with one-sided 2 sigma upper-limits of: h_c <= 10.98 [10^{-15}], h_c <= 60.29 [10^{-15}], and h_c <= 5.65 [10^{-15}]

P62 accumulates through neuroanatomical circuits in response to tauopathy propagation

In Alzheimer's disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies

Virtual 3D planning and prediction accuracy in two bimaxillary face transplantations in Helsinki

Conclusions: 3D planning is feasible , provides close to accurate bone reconstruction in face transplantation. Preoperative virtual transplantation assists planning and improves the outcome in bimaxillary face transplantation. (c) 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )Peer reviewe

The noise properties of 42 millisecond pulsars from the European Pulsar Timing Array and their impact on gravitational wave searches

The sensitivity of Pulsar Timing Arrays to gravitational waves depends on the noise present in the individual pulsar timing data. Noise may be either intrinsic or extrinsic to the pulsar. Intrinsic sources of noise will include rotational instabilities, for example. Extrinsic sources of noise include contributions from physical processes which are not sufficiently well modelled, for example, dispersion and scattering effects, analysis errors and instrumental instabilities. We present the results from a noise analysis for 42 millisecond pulsars (MSPs) observed with the European Pulsar Timing Array. For characterising the low-frequency, stochastic and achromatic noise component, or "timing noise", we employ two methods, based on Bayesian and frequentist statistics. For 25 MSPs, we achieve statistically significant measurements of their timing noise parameters and find that the two methods give consistent results. For the remaining 17 MSPs, we place upper limits on the timing noise amplitude at the 95% confidence level. We additionally place an upper limit on the contribution to the pulsar noise budget from errors in the reference terrestrial time standards (below 1%), and we find evidence for a noise component which is present only in the data of one of the four used telescopes. Finally, we estimate that the timing noise of individual pulsars reduces the sensitivity of this data set to an isotropic, stochastic GW background by a factor of >9.1 and by a factor of >2.3 for continuous GWs from resolvable, inspiralling supermassive black-hole binaries with circular orbits.Comment: Accepted for publication by the Monthly Notices of the Royal Astronomical Societ

Oncolytic adenovirus shapes the ovarian tumor microenvironment for potent tumor-infiltrating lymphocyte tumor reactivity

BACKGROUND: Ovarian cancers often contain significant numbers of tumor-infiltrating lymphocytes (TILs) that can be readily harnessed for adoptive T-cell therapy (ACT). However, the immunosuppressive ovarian tumor microenvironment and lack of tumor reactivity in TILs can limit the effectiveness of the therapy. We hypothesized that by using an oncolytic adenovirus (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) to deliver tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2), we could counteract immunosuppression, and enhance antitumor TIL responses in ovarian cancer (OVCA). METHODS: We established ex vivo tumor cultures freshly derived from patients with advanced OVCA and evaluated the effects of Ad5/3-E2F-D24-hTNFa-IRES-hIL2 or Ad5/3-E2F-D24 (the control virus without TNFa and IL-2) on TILs, cytokine response and tumor viability. Tumor reactivity was assessed by determining interferon gamma (IFNg) response of clinically relevant TILs towards autologous T-cell-depleted ex vivo tumor cultures pretreated with or without the aforementioned oncolytic adenoviruses. RESULTS: Treatment of ex vivo tumor cultures with Ad5/3-E2F-D24-hTNFa-IRES-hIL2 caused a substantial rise in proinflammatory signals: increased secretion of IFNg, CXCL10, TNFa and IL-2, and concomitant activation of CD4+ and CD8+ TILs. Potent tumor reactivity was seen, as clinically relevant TIL secreted high levels of IFNg in response to autologous T-cell-depleted ovarian ex vivo tumor cultures treated with Ad5/3-E2F-D24-hTNFa-IRES-hIL2. This phenomenon was independent of PD-L1 expression in tumor cells, a factor that determined the variability of IFNg responses seen in different patient samples. CONCLUSIONS: Overall, oncolytic adenovirus Ad5/3-E2F-D24-hTNFa-IRES-hIL2 was able to rewire the ovarian tumor microenvironment to accommodate heightened antitumor TIL reactivity. Such effects may improve the clinical effectiveness of ACT with TILs in patients with advanced OVCA.Peer reviewe

Bronchoalveolar lavage fluid from preterm infants with chorioamnionitis inhibits alveolar epithelial repair

<p>Abstract</p> <p>Background</p> <p>Preterm infants are highly susceptible to lung injury. While both chorioamnionitis and antenatal steroids induce lung maturation, chorioamnionitis is also associated with adverse lung development. We investigated the ability of bronchoalveolar lavage fluid (BALF) from ventilated preterm infants to restore alveolar epithelial integrity after injury <it>in vitro</it>, depending on whether or not they were exposed to chorioamnionitis or antenatal steroids. For this purpose, a translational model for alveolar epithelial repair was developed and characterised.</p> <p>Methods</p> <p>BALF was added to mechanically wounded monolayers of A549 cells. Wound closure was quantified over time and compared between preterm infants (gestational age < 32 wks) exposed or not exposed to chorioamnionitis and antenatal steroids (≥ 1 dose). Furthermore, keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) were quantified in BALF, and their ability to induce alveolar epithelial repair was evaluated in the model.</p> <p>Results</p> <p>On day 0/1, BALF from infants exposed to antenatal steroids significantly increased epithelial repair (40.3 ± 35.5 vs. -6.3 ± 75.0% above control/mg protein), while chorioamnionitis decreased wound-healing capacity of BALF (-2.9 ± 87.1 vs. 40.2 ± 36.9% above control/mg protein). BALF from patients with chorioamnionitis contained less KGF (11 (0-27) vs. 0 (0-4) pg/ml) and less detectable VEGF (66 vs. 95%) on day 0. BALF levels of VEGF and KGF correlated with its ability to induce wound repair. Moreover, KGF stimulated epithelial repair dose-dependently, although the low levels in BALF suggest KGF is not a major modulator of BALF-induced wound repair. VEGF also stimulated alveolar epithelial repair, an effect that was blocked by addition of soluble VEGF receptor-1 (sVEGFr1/Flt-1). However, BALF-induced wound repair was not significantly affected by addition of sVEGFr1.</p> <p>Conclusion</p> <p>Antenatal steroids improve the ability of BALF derived from preterm infants to stimulate alveolar epithelial repair <it>in vitro</it>. Conversely, chorioamnionitis is associated with decreased wound-healing capacity of BALF. A definite role for KGF and VEGF in either process could not be established. Decreased ability to induce alveolar epithelial repair after injury may contribute to the association between chorioamnionitis and adverse lung development in mechanically ventilated preterm infants.</p

Fitomassa de adubos verdes e controle de plantas daninhas em diferentes densidades populacionias de leguminosas.

O objetivo deste trabalho foi avaliar a fitomassa de calopogônio, mucuna-preta, mucunarajada,feijão-de-porco, guandu de porte alto, Crotalaria spectabilis e C. breviflora sob diferentes densidades de semeadura (10, 20, 40, 80 e 160 sementes viáveis m-2), e o crescimento de plantas daninhas nessas densidades, em área de tabuleiros costeiros. O experimento foi desenvolvido de maio a agosto de 1996, no Campo Experimental “Antônio Martins”(EMDAGRO/Embrapa-CPATC), em Lagarto, SE. O número de plantas vivas na floração (NPVF) e a matéria seca da parte aérea das leguminosas (MSPA) foram determinados quando, em cada espécie, cerca de 50% das plantas floresceram. Maiores incrementos de MSPA, em resposta ao adensamento populacional, foram observados em C. spectabilis e C. breviflora, seguidas pelo calopogônio, mucuna-preta e mucuna-rajada. Em relação ao feijão-de-porco, a resposta foi negativa, enquanto com o guandu não houve influência. Quanto ao NPVF, as respostas ao adensamento foram lineares e positivas em C. spectabilis, C. breviflora e calopogônio, e quadráticas com ponto de máxima em feijão-de-porco,guandu e mucuna-rajada. Embora nenhum modelo tenha sido ajustado para expressar a relação entre NPVF e adensamento na semeadura de mucuna-preta, a sobrevivência dessa espécie foi reduzida em todas as densidades. Maiores inibições de plantas daninhas ocorreram nas parcelas de mucuna-preta e feijão-de-porco

The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions

Aims: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. Methods and results: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). Conclusion: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF