Physical Education 2

Exam paper for first semester 201

Mycobacterium tuberculosis proteins involved in cell wall lipid biosynthesis improve BCG vaccine efficacy in a murine TB model

OBJECTIVES: Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant. METHODS: Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later. Immune responses were examined at given time points. 9 weeks post vaccination, mice were aerosol-challenged with M. tb, and sacrificed at 6 and 12 weeks to assess bacterial burden. RESULTS: Vaccination of mice with BCG and M. tb proteins in the presence of GLA-SE adjuvant triggered strong IFN-γ and IL-2 production by splenocytes; more TNF-α was produced without GLA-SE addition. Antibody responses to all three antigens did not differ, with or without GLA-SE adjuvant. Protein boosting without GLA-SE adjuvant resulted in vaccinated animals having better control of pulmonary M. tb load at 6 and 12 weeks post aerosol infection, while animals receiving the protein boost with GLA-SE adjuvant exhibited more bacteria in the lungs. CONCLUSIONS: Our data provides evidence for developing Rv2958c, Rv2957 and Rv0447c in a heterologous prime-boost vaccination strategy with BCG

Characterizing planetary systems with SPIRou: M-dwarf planet-search survey and the multiplanet systems GJ 876 and GJ 1148

SPIRou is a near-infrared spectropolarimeter and a high-precision velocimeter. The SPIRou Legacy Survey collected data from February 2019 to June 2022, half of the time devoted to a blind search for exoplanets around nearby cool stars. The aim of this paper is to present this program and an overview of its properties, and to revisit the radial velocity (RV) data of two multiplanet systems, including new visits with SPIRou. From SPIRou data, we can extract precise RVs using efficient telluric correction and line-by-line measurement techniques, and we can reconstruct stellar magnetic fields from the collection of polarized spectra using the Zeeman-Doppler imaging method. The stellar sample of our blind search in the solar neighborhood, the observing strategy, the RV noise estimates, chromatic behavior, and current limitations of SPIRou RV measurements on bright M dwarfs are described. In addition, SPIRou data over a 2.5-year time span allow us to revisit the known multiplanet systems GJ~876 and GJ~1148. For GJ~876, the new dynamical analysis including the four planets is consistent with previous models and confirms that this system is deep in the Laplace resonance and likely chaotic. The large-scale magnetic map of GJ~876 over two consecutive observing seasons is obtained and shows a dominant dipolar field with a polar strength of 30~G, which defines the magnetic environment in which the inner planet with a period of 1.94~d is embedded. For GJ~1148, we refine the known two-planet model.Comment: accepted in A&

Accuracy of syndrome definitions based on diagnoses in physician claims

<p>Abstract</p> <p>Background</p> <p>Community clinics offer potential for timelier outbreak detection and monitoring than emergency departments. However, the accuracy of syndrome definitions used in surveillance has never been evaluated in community settings. This study's objective was to assess the accuracy of syndrome definitions based on diagnostic codes in physician claims for identifying 5 syndromes (fever, gastrointestinal, neurological, rash, and respiratory including influenza-like illness) in community clinics.</p> <p>Methods</p> <p>We selected a random sample of 3,600 community-based primary care physicians who practiced in the fee-for-service system in the province of Quebec, Canada in 2005-2007. We randomly selected 10 visits per physician from their claims, stratifying on syndrome type and presence, diagnosis, and month. Double-blinded chart reviews were conducted by telephone with consenting physicians to obtain information on patient diagnoses for each sampled visit. The sensitivity, specificity, and positive predictive value (PPV) of physician claims were estimated by comparison to chart review.</p> <p>Results</p> <p>1,098 (30.5%) physicians completed the chart review. A chart entry on the date of the corresponding claim was found for 10,529 (95.9%) visits. The sensitivity of syndrome definitions based on diagnostic codes in physician claims was low, ranging from 0.11 (fever) to 0.44 (respiratory), the specificity was high, and the PPV was moderate to high, ranging from 0.59 (fever) to 0.85 (respiratory). We found that rarely used diagnostic codes had a higher probability of being false-positives, and that more commonly used diagnostic codes had a higher PPV.</p> <p>Conclusions</p> <p>Future research should identify physician, patient, and encounter characteristics associated with the accuracy of diagnostic codes in physician claims. This would enable public health to improve syndromic surveillance, either by focusing on physician claims whose diagnostic code is more likely to be accurate, or by using all physician claims and weighing each according to the likelihood that its diagnostic code is accurate.</p

Wapiti\texttt{Wapiti}: a data-driven approach to correct for systematics in RV data -- Application to SPIRou data of the planet-hosting M dwarf GJ 251

Context: Recent advances in the development of precise radial velocity (RV) instruments in the near-infrared (nIR) domain, such as SPIRou, have facilitated the study of M-type stars to more effectively characterize planetary systems. However, the nIR presents unique challenges in exoplanet detection due to various sources of planet-independent signals which can result in systematic errors in the RV data. Aims: In order to address the challenges posed by the detection of exoplanetary systems around M-type stars using nIR observations, we introduce a new data-driven approach for correcting systematic errors in RV data. The effectiveness of this method is demonstrated through its application to the star GJ 251. Methods: Our proposed method, referred to as $\texttt{Wapiti}$ (Weighted principAl comPonent analysIs reconsTructIon), uses a dataset of per-line RV time-series generated by the line-by-line (LBL) algorithm and employs a weighted principal component analysis (wPCA) to reconstruct the original RV time-series. A multi-step process is employed to determine the appropriate number of components, with the ultimate goal of subtracting the wPCA reconstruction of the per-line RV time-series from the original data in order to correct systematic errors. Results: The application of $\texttt{Wapiti}$ to GJ 251 successfully eliminates spurious signals from the RV time-series and enables the first detection in the nIR of GJ 251b, a known temperate super-Earth with an orbital period of 14.2 days. This demonstrates that, even when systematics in SPIRou data are unidentified, it is still possible to effectively address them and fully realize the instrument's capability for exoplanet detection. Additionally, in contrast to the use of optical RVs, this detection did not require to filter out stellar activity, highlighting a key advantage of nIR RV measurements.Comment: Submitted to A&A. For the publicly available Wapiti code, see https://github.com/HkmMerwan/wapit

The magnetic field and multiple planets of the young dwarf AU~Mic

In this paper we present an analysis of near-infrared spectropolarimetric and velocimetric data of the young M dwarf AU Mic, collected with SPIRou at the Canada-France-Hawaii telescope from 2019 to 2022, mostly within the SPIRou Legacy Survey. With these data, we study the large- and small-scale magnetic field of AU Mic, detected through the unpolarized and circularly-polarized Zeeman signatures of spectral lines. We find that both are modulated with the stellar rotation period (4.86 d), and evolve on a timescale of months under differential rotation and intrinsic variability. The small-scale field, estimated from the broadening of spectral lines, reaches $2.61\pm0.05$ kG. The large-scale field, inferred with Zeeman-Doppler imaging from Least-Squares Deconvolved profiles of circularly-polarized and unpolarized spectral lines, is mostly poloidal and axisymmetric, with an average intensity of $550\pm30$ G. We also find that surface differential rotation, as derived from the large-scale field, is $\simeq$30% weaker than that of the Sun. We detect the radial velocity (RV) signatures of transiting planets b and c, although dwarfed by activity, and put an upper limit on that of candidate planet d, putatively causing the transit-timing variations of b and c. We also report the detection of the RV signature of a new candidate planet (e) orbiting further out with a period of $33.39\pm0.10$ d, i.e., near the 4:1 resonance with b. The RV signature of e is detected at 6.5$\sigma$ while those of b and c show up at $\simeq$4$\sigma$, yielding masses of $10.2^{+3.9}_{-2.7}$ and $14.2^{+4.8}_{-3.5}$ Earth masses for b and c, and a minimum mass of $35.2^{+6.7}_{-5.4}$ Earth masses for e.Comment: MNRAS, in press (20 pages and 12 figures + 9 pages of supplementary material

Monitoring the large-scale magnetic field of AD~Leo with SPIRou, ESPaDOnS and Narval. Toward a magnetic polarity reversal?

One manifestation of dynamo action on the Sun is the 22-yr magnetic cycle, exhibiting a polarity reversal and a periodic conversion between poloidal and toroidal fields. For M dwarfs, several authors claim evidence of activity cycles from photometry and analyses of spectroscopic indices, but no clear polarity reversal has been identified from spectropolarimetric observations. Our aim is to monitor the evolution of the large-scale field of AD Leo, which has shown hints of a secular evolution from past dedicated spectropolarimetric campaigns. We analysed near-infrared spectropolarimetric observations of the active M dwarf AD Leo taken with SPIRou between 2019 and 2020 and archival optical data collected with ESPaDOnS and Narval between 2006 and 2019. We searched for long-term variability in the longitudinal field, the width of unpolarised Stokes profiles, the unsigned magnetic flux derived from Zeeman broadening, and the geometry of the large-scale magnetic field using both Zeeman-Doppler Imaging and Principal Component Analysis. We found evidence of a long-term evolution of the magnetic field, featuring a decrease in axisymmetry (from 99% to 60%). This is accompanied by a weakening of the longitudinal field (-300 to -50 G) and a correlated increase in the unsigned magnetic flux (2.8 to 3.6 kG). Likewise, the width of the mean profile computed with selected near-infrared lines manifests a long-term evolution corresponding to field strength changes over the full time series, but does not exhibit modulation with the stellar rotation of AD Leo in individual epochs. The large-scale magnetic field of AD Leo manifested first hints of a polarity reversal in late 2020 in the form of a substantially increased dipole obliquity, while the topology remained predominantly poloidal and dipolar. This suggests that low-mass M dwarfs with a dipole-dominated magnetic field can undergo magnetic cycles.Comment: 26 pages, 18 figures, 8 table

Calcitonin gene-related peptide stimulates proliferation of alveolar epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A549 cells were cultured in Dulbecco Modified Eagle Medium with 5% fatal bovin serum for 24 hours, then CGRP was added <it>in vitro</it>. The proliferation of DNA synthesis was measured using 5-bromo-2-deoxyuridine, an analog of thymidine, by enzyme-linked immunosorbent assay.</p> <p>As one intracellular response to CGRP, we examined activation of p44/42- extracellular signal-regulated kinase (ERK) pathway by adding CGRP, using western blotting method.</p> <p>Recombinant adenovirus encoding nuclear-targeted-human β-CGRP (rhCGRP) was administered into Male Wister rat (n = 5, 10 weeks old) lungs by intratracheal instillation <it>in vivo</it>. 7 days after the administration of CGRP, rat lungs were harvested and histological findings and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) were evaluated to examine cell proliferation.</p> <p>Results</p> <p><it>In vitro </it>study, CGRP increased the proliferation of A549 cells in a dose and time dependent manner. CGRP8-37 (inhibitor of CGRP receptor) decreased CGRP induced proliferation of DNA synthesis. Phosphorylation of ERK pathway was observed within 15 minutes and peaked in one hour. U0126 (inhibitor of ERK pathway) decreased CGRP induced proliferation of DNA synthesis.<it>In vivo </it>study, histological examination of the lung indicated proliferation of alveolar epithelial cells in the rhCGRP-treated group and the nuclei of alveolar epithelial cells were positive for PCNA immunostaining.</p> <p>Conclusion</p> <p>In this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells <it>in vivo </it>and <it>in vitro</it>.</p

Near-IR and optical radial velocities of the active M-dwarf star Gl 388 (AD Leo) with SPIRou at CFHT and SOPHIE at OHP

Context: The search for extrasolar planets around the nearest M-dwarfs is a crucial step towards identifying the nearest Earth-like planets. One of the main challenges in this search is that M-dwarfs can be magnetically active and stellar activity can produce radial velocity (RV) signals that could mimic those of a planet. Aims: We aim to investigate whether the 2.2 day period observed in optical RVs of the nearby active M-dwarf star Gl 388 (AD Leo) is due to stellar activity or to a planet which co-rotates with the star as suggested in the past. Methods: We obtained quasi-simultaneous optical RVs of Gl 388 from 2019 to 2021 with SOPHIE (R$\sim$75k) at the OHP in France, and near-IR RV and Stokes V measurements with SPIRou at the CFHT (R$\sim$70k). Results: The SOPHIE RV time-series displays a periodic signal with 2.23$\pm$0.01 days period and 23.6$\pm$0.5 m/s amplitude, which is consistent with previous HARPS observations obtained in 2005-2006. The SPIRou RV time-series is flat at 5 m/s rms and displays no periodic signals. RV signals of amplitude higher than 5.3 m/s at a period of 2.23 days can be excluded with a confidence level higher than 99%. Using the modulation of the longitudinal magnetic field (Bl) measured with SPIRou, we derive a stellar rotation period of 2.2305$\pm$0.0016 days. Conclusions: SPIRou RV measurements provide solid evidence that the periodic variability of the optical RVs of Gl 388 is due to stellar activity rather than to a co-rotating planet. The magnetic activity nature of the optical RV signal is further confirmed by the modulation of Bl with the same period. The SPIRou campaign on Gl 388 demonstrates the power of near-IR RV to confirm or infirm planet candidates discovered in the optical around active stars. SPIRou observations reiterate how effective spectropolarimetry is at determining the stellar rotation period.Comment: 25 pages, 23 figures, Accepted by Astronomy and Astrophysic