Non-linear Spectroscopy of Sr Atoms in an Optical Cavity for Laser Stabilization

We study the non-linear interaction of a cold sample of strontium-88 atoms coupled to a single mode of a low finesse optical cavity in the so-called bad cavity limit and investigate the implications for applications to laser stabilization. The atoms are probed on the weak inter-combination line \lvert 5s^{2} \, ^1 \textrm{S}_0 \rangle \,-\, \lvert 5s5p \, ^3 \textrm{P}_1 \rangle at 689 nm in a strongly saturated regime. Our measured observables include the atomic induced phase shift and absorption of the light field transmitted through the cavity represented by the complex cavity transmission coefficient. We demonstrate high signal-to-noise-ratio measurements of both quadratures - the cavity transmitted phase and absorption - by employing FM spectroscopy (NICE-OHMS). We also show that when FM spectroscopy is employed in connection with a cavity locked to the probe light, observables are substantially modified compared to the free space situation where no cavity is present. Furthermore, the non-linear dynamics of the phase dispersion slope is experimentally investigated and the optimal conditions for laser stabilization are established. Our experimental results are compared to state-of-the-art cavity QED theoretical calculations.Comment: 7 pages, 4 figure

Observation of Motion Dependent Nonlinear Dispersion with Narrow Linewidth Atoms in an Optical Cavity

As an alternative to state-of-the-art laser frequency stabilisation using ultra-stable cavities, it has been proposed to exploit the non-linear effects from coupling of atoms with a narrow transition to an optical cavity. Here we have constructed such a system and observed non-linear phase shifts of a narrow optical line by strong coupling of a sample of strontium-88 atoms to an optical cavity. The sample temperature of a few mK provides a domain where the Doppler energy scale is several orders of magnitude larger than the narrow linewidth of the optical transition. This makes the system sensitive to velocity dependent multi-photon scattering events (Dopplerons) that affect the cavity field transmission and phase. By varying the number of atoms and the intra-cavity power we systematically study this non-linear phase signature which displays roughly the same features as for much lower temperature samples. This demonstration in a relatively simple system opens new possibilities for alternative routes to laser stabilization at the sub 100 mHz level and superradiant laser sources involving narrow line atoms. The understanding of relevant motional effects obtained here has direct implications for other atomic clocks when used in relation with ultranarrow clock transitions.Comment: 9 pages (including 4 pages of Supplemental Information), 6 figures. Updated to correspond to the published versio

Chronic cerebral hypoperfusion alters amyloid-β peptide pools leading to cerebral amyloid angiopathy, microinfarcts and hemorrhages in Tg-SwDI mice

Cerebral hypoperfusion is an early feature of Alzheimer’s disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesized that cerebral hypoperfusion promotes the accumulation of amyloid-β (Aβ) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this, we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Aβ peptide pools in a transgenic mouse model of AD (transgenic mice with Swedish, Dutch and Iowa mutations in human amyloid precursor protein (APP) (Tg-SwDI)). Cerebrovascular integrity was characterized by quantifying the occurrence of microinfarcts and haemorrhages and compared with wild-type mice without Aβ. A significant increase in soluble Aβ peptides (Aβ40/42) was detected after 1 month of hypoperfusion in the parenchyma in parallel with elevated APP and APP proteolytic products. Following 3 months, a significant increase in insoluble Aβ40/42 was determined in the parenchyma and vasculature. Microinfarct load was significantly increased in the Tg-SwDI as compared with wild-type mice and further exacerbated by hypoperfusion at 1 and 3 months. In addition, the number of Tg-SwDI hypoperfused mice with haemorrhages was increased compared with hypoperfused wild-type mice. Soluble parenchymal Aβ was associated with elevated NADPH oxidase-2 (NOX2) which was exacerbated by 1-month hypoperfusion. We suggest that in response to hypoperfusion, increased Aβ production/deposition may contribute to degenerative processes by triggering oxidative stress promoting cerebrovascular disruption and the development of microinfarcts.</jats:p

Implications for migraine

Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Margarida Martins-Oliveira is grateful to the Portuguese Fundação para a Ciência e Tecnologia (FCT) for its support with an individual PhD grant (SFRH/BD/77127/2011). The conduct of the research was financially supported by the EUROHEADPAIN European Union FP7 (PJG & PRH: 602633), the Wellcome Trust (PJG: 104033) and the Medical Research Council (PRH: MR/P006264/1). Publisher Copyright: © International Headache Society 2022.Background: Imaging migraine premonitory studies show increased midbrain activation consistent with the ventral tegmental area, an area involved in pain modulation and hedonic feeding. We investigated ventral tegmental area pharmacological modulation effects on trigeminovascular processing and consequent glycemic levels, which could be involved in appetite changes in susceptible migraine patients. Methods: Serotonin and pituitary adenylate cyclase-activating polypeptide receptors immunohistochemistry was performed in ventral tegmental area parabrachial pigmented nucleus of male Sprague Dawley rats. In vivo trigeminocervical complex neuronal responses to dura mater nociceptive electrical stimulation, and facial mechanical stimulation of the ophthalmic dermatome were recorded. Changes in trigeminocervical complex responses following ventral tegmental area parabrachial pigmented nucleus microinjection of glutamate, bicuculline, naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole were measured, and blood glucose levels assessed pre- and post-microinjection. Results: Glutamatergic stimulation of ventral tegmental area parabrachial pigmented nucleus neurons reduced nociceptive and spontaneous trigeminocervical complex neuronal firing. Naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole inhibited trigeminovascular spontaneous activity, and trigeminocervical complex neuronal responses to dural-evoked electrical and mechanical noxious stimulation. Trigeminovascular sensory processing through modulation of the ventral tegmental area parabrachial pigmented nucleus resulted in reduced circulating glucose levels. Conclusion: Pharmacological modulation of ventral tegmental area parabrachial pigmented nucleus neurons elicits changes in trigeminovascular sensory processing. The interplay between ventral tegmental area parabrachial pigmented nucleus activity and the sensory processing by the trigeminovascular system may be relevant to understand associated sensory and homeostatic symptoms in susceptible migraine patients.publishersversioninpres

Neuroendocrine signaling modulates specific neural networks relevant to migraine

Migraine is a disabling brain disorder involving abnormal trigeminovascular activation and sensitization. Fasting or skipping meals is considered a migraine trigger and altered fasting glucose and insulin levels have been observed in migraineurs. Therefore peptides involved in appetite and glucose regulation including insulin, glucagon and leptin could potentially influence migraine neurobiology. We aimed to determine the effect of insulin (10 U·kg(− 1)), glucagon (100 μg·200 μl(− 1)) and leptin (0.3, 1 and 3 mg·kg(− 1)) signaling on trigeminovascular nociceptive processing at the level of the trigeminocervical-complex and hypothalamus. Male rats were anesthetized and prepared for craniovascular stimulation. In vivo electrophysiology was used to determine changes in trigeminocervical neuronal responses to dural electrical stimulation, and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) immunohistochemistry to determine trigeminocervical and hypothalamic neural activity; both in response to intravenous administration of insulin, glucagon, leptin or vehicle control in combination with blood glucose analysis. Blood glucose levels were significantly decreased by insulin (p < 0.001) and leptin (p < 0.01) whereas glucagon had the opposite effect (p < 0.001). Dural-evoked neuronal firing in the trigeminocervical-complex was significantly inhibited by insulin (p < 0.001), glucagon (p < 0.05) and leptin (p < 0.01). Trigeminocervical-complex pERK1/2 cell expression was significantly decreased by insulin and leptin (both p < 0.001), and increased by glucagon (p < 0.001), when compared to vehicle control. However, only leptin affected pERK1/2 expression in the hypothalamus, significantly decreasing pERK1/2 immunoreactive cell expression in the arcuate nucleus (p < 0.05). These findings demonstrate that insulin, glucagon and leptin can alter the transmission of trigeminal nociceptive inputs. A potential neurobiological link between migraine and impaired metabolic homeostasis may occur through disturbed glucose regulation and a transient hypothalamic dysfunction

Spitzer Mid-Infrared Spectroscopy of Infrared Luminous Galaxies at z~2 III: Far-IR to Radio Properties and Optical Spectral Diagnostics

We present the far-IR, millimeter, and radio photometry as well as optical and near-IR spectroscopy of a sample of 48 z~1-3 Spitzer-selected ULIRGs with IRS mid-IR spectra. Our goals are to compute their bolometric emission, and to determine both the presence and relative strength of their AGN and starburst components. We find that strong-PAH sources tend to have higher 160um and 1.2mm fluxes than weak-PAH sources. The depth of the 9.7um silicate feature does not affect MAMBO detectability. We fit the far-IR SEDs of our sample and find an average ~7x10^{12}Lsun for our z>1.5 sources. Spectral decomposition suggests that strong-PAH sources typically have ~20-30% AGN fractions. Weak-PAH sources by contrast tend to have >~70% AGN fractions, with a few sources having comparable contributions of AGN and starbursts. The optical line diagnostics support the presence of AGN in the bulk of the weak-PAH sources. With one exception, our sources are narrow-line sources, show no obvious correspondence between the optical extinction and the silicate feature depth, and, in two cases, show evidence for outflows. Radio AGN are present in both strong-PAH and weak-PAH sources. This is supported by our sample's far-IR-to-radio ratios (q) being consistently below the average value of 2.34 for local star-forming galaxies. We use survival analysis to include the lower-limits given by the radio-undetected sources, arriving at =2.07+/-0.01 for our z>1.5 sample. In total, radio and, where available, optical line diagnostics support the presence of AGN in 57% of the z>1.5 sources, independent of IR-based diagnostics. For higher-z sources, the AGN luminosities alone are estimated to be >10^{12}Lsun, which, supported by the [OIII] luminosities, implies that the bulk of our sources host obscured quasars.Comment: 22 pages, 14 figures, accepted for publication in Ap

Pulmonary Artery Acceleration Time Provides a Reliable Estimate of Invasive Pulmonary Hemodynamics in Children

Background Pulmonary artery acceleration time (PAAT) is a non-invasive method to assess pulmonary hemodynamics, but lacks validity in children. This study sought to evaluate the accuracy of Doppler echocardiography (DE) derived PAAT in predicting right heart catheterization (RHC) derived pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and compliance in children. Methods Prospectively acquired and retrospectively measured DE derived PAAT and RHC derived systolic PAP (sPAP), mean PAP (mPAP), index PVR (PVRi) and compliance were compared by regression analysis in a derivation cohort of 75 children (median age, 5.3 years; 1.3–12.6) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricle ejection time (RVET) and corrected by the RR interval. Regression equations incorporating PAAT and PAAT:RVET from the derivation cohort were then evaluated for the accuracy of its predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight- matched children with elevated PAP and PVR. Results There were significant inverse correlations between PAAT and RHC derived mPAP (r = −0.82) and PVRi (r= −0.78) and direct correlation (r= 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 WU x m2 and mPAP > 25 mmHg), PAAT < 90 msec and PAAT:RVET < 0.31 resulted in a sensitivity of 97% and a specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were: mPAP = 48 – 0.28 x PAAT and PVRi = 9 –0.07 x PAAT. These PAAT integrated equations predicted RHC measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88, 0.83 respectively), small biases (<10%), and minimal coefficient of variation (<8%). Conclusions PAAT inversely correlates with RHC measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT based regression equations in children to accurately predict RHC derived PAP and PVR

Markers of Maternal and Infant Metabolism are Associated with Ventricular Dysfunction in Infants of Obese Women with Type 2 Diabetes

BACKGROUND To test the hypothesis that infants born to obese women with pregestational type 2 diabetes mellitus (IBDM) have ventricular dysfunction at one month that is associated with markers of maternal lipid and glucose metabolism. METHODS In a prospective observational study of IBDM (OB+DM, n=25), echocardiography measures of septal, left (LV) and right ventricular (RV) function and structure were compared at one month of age to infants born to OB mothers without DM (OB, n=24), and non-OB without DM (Lean, n=23). Basal maternal lipid and glucose kinetics and maternal plasma and infant (cord) plasma were collected for hormone and cytokine analyses. RESULTS RV, LV, and septal strain measures were lower in the OB+DM infants vs. other groups, without evidence of septal hypertrophy. Maternal hepatic insulin sensitivity, maternal plasma free fatty acid concentration, and cord plasma insulin and leptin most strongly predicted decreased septal strain in the OB+DM infants. CONCLUSION IBDM’s have reduced septal function at one month in the absence of septal hypertrophy, which is associated with altered maternal and infant lipid and glucose metabolism. These findings suggest that maternal obesity and DM may have a prolonged impact on the cardiovascular health of their offspring, despite resolution of cardiac hypertrophy