Two-photon spectroscopy of trapped HD+^+ ions in the Lamb-Dicke regime

We study the feasibility of nearly-degenerate two-photon rovibrational spectroscopy in ensembles of trapped, sympathetically cooled hydrogen molecular ions using a resonance-enhanced multiphoton dissociation (REMPD) scheme. Taking advantage of quasi-coincidences in the rovibrational spectrum, the excitation lasers are tuned close to an intermediate level to resonantly enhance two-photon absorption. Realistic simulations of the REMPD signal are obtained using a four-level model that takes into account saturation effects, ion trajectories, laser frequency noise and redistribution of population by blackbody radiation. We show that the use of counterpropagating laser beams enables optical excitation in an effective Lamb-Dicke regime. Sub-Doppler lines having widths in the 100 Hz range can be observed with good signal-to-noise ratio for an optimal choice of laser detunings. Our results indicate the feasibility of molecular spectroscopy at the $10^{-14}$ accuracy level for improved tests of molecular QED, a new determination of the proton-to-electron mass ratio, and studies of the time (in)dependence of the latter.Comment: 16 pages, 17 figure

Knockout of arsenic (+3 oxidation state) methyltransferase results in sex-dependent changes in phosphatidylcholine metabolism in mice

Arsenic (+3 oxidation state) methyltransferase is the key enzyme in the methylation pathway for inorganic arsenic. We have recently shown that As3mt knockout (KO) has a profound effect on metabolomic profiles in mice. Phosphatidylcholine species (PCs) were the largest group of metabolites altered in both plasma and urine. The present study used targeted analysis to investigate the KO-associated changes in PC profiles in the liver, the site of PC synthesis. Results show that As3mt KO has a systemic effect on PC metabolism and that this effect is sex dependent

Observation of longitudinal and transverse self-injections in laser-plasma accelerators

Laser-plasma accelerators can produce high quality electron beams, up to giga-electronvolts in energy, from a centimeter scale device. The properties of the electron beams and the accelerator stability are largely determined by the injection stage of electrons into the accelerator. The simplest mechanism of injection is self-injection, in which the wakefield is strong enough to trap cold plasma electrons into the laser wake. The main drawback of this method is its lack of shot-to-shot stability. Here we present experimental and numerical results that demonstrate the existence of two different self-injection mechanisms. Transverse self-injection is shown to lead to low stability and poor quality electron beams, because of a strong dependence on the intensity profile of the laser pulse. In contrast, longitudinal injection, which is unambiguously observed for the first time, is shown to lead to much more stable acceleration and higher quality electron beams.Comment: 7 pages, 7 figure

Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation

Sex-dependent effects of preconception exposure to arsenite on gene transcription in parental germ cells and on transcriptomic profiles and diabetic phenotype of offspring

Chronic exposure to inorganic arsenic (iAs) has been linked to diabetic phenotypes in both humans and mice. However, diabetogenic effects of iAs exposure during specific developmental windows have never been systematically studied. We have previously shown that in mice, combined preconception and in utero exposures to iAs resulted in impaired glucose homeostasis in male offspring. The goal of the present study was to determine if preconception exposure alone can contribute to this outcome. We have examined metabolic phenotypes in male and female offspring from dams and sires that were exposed to iAs in drinking water (0 or 200 μg As/L) for 10 weeks prior to mating. The effects of iAs exposure on gene expression profiles in parental germ cells, and pancreatic islets and livers from offspring were assessed using RNA sequencing. We found that iAs exposure significantly altered transcript levels of genes, including diabetes-related genes, in the sperm of sires. Notably, some of the same gene transcripts and the associated pathways were also altered in the liver of the offspring. The exposure had a more subtle effect on gene expression in maternal oocytes and in pancreatic islets of the offspring. In female offspring, the preconception exposure was associated with increased adiposity, but lower blood glucose after fasting and after glucose challenge. HOMA-IR, the indicator of insulin resistance, was also lower. In contrast, the preconception exposure had no effects on blood glucose measures in male offspring. However, males from parents exposed to iAs had higher plasma insulin after glucose challenge and higher insulinogenic index than control offspring, indicating a greater requirement for insulin to maintain glucose homeostasis. Our results suggest that preconception exposure may contribute to the development of diabetic phenotype in male offspring, possibly mediated through germ cell-associated inheritance. Future research can investigate role of epigenetics in this phenomenon. The paradoxical outcomes in female offspring, suggesting a protective effect of the preconception exposure, warrant further investigation

Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure

Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in GoÌmez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure

French political science at a turning point

This paper outlines the origins and institutionalization process of French political science since 1945. It sketches the present state of the discipline, and it analyses recent trends that appear almost as a form of ‘de-institutionalization’. Overall, the discipline is quite well entrenched and is independent in terms of recruitment with its own teaching and research branches. However, political scientists suffer from a relative lack of visibility in the public space in comparison with their colleagues from more prominent disciplines. In many fields French political science remains invisible at the international level, though this may change considerably in the years to come. The main element of uncertainty comes from the ongoing reforms, the redefinition of the partnership between universities, the Instituts d'Etudes Politiques and the CNRS, and the way the autonomy of universities will be implemented

Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment

We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment

Safety of the Combination of PERC and YEARS Rules in Patients With Low Clinical Probability of Pulmonary Embolism: A Retrospective Analysis of Two Large European Cohorts

BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED). METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson\u27s continuity correction. RESULTS: We analyzed 1,951 patients (mean ± SD age = 47 ± 18 years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI = 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI = 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI = 45%-54%], absolute reduction 13% (95% CI = 11%-14%]). CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA