Atmospheric concentrations of carbon dioxide and its isotopic composition in southern Poland: comparison of high-altitude mountain site and a near-by urban environment

International audienceThe results of regular observations of atmospheric CO2 mixing ratios and its carbon isotope composition (?13C, ?14C), carried out at two continental sites located in central Europe are presented and discussed. The sites (Kasprowy Wierch, 49°14' N, 19°59' E, 1989 m a.s.l.; Krakow, 50°04' N, 19°55' E, 220 m a.s.l.), are located in two contrasting environments: (i) high-altitude mountaneous area, relatively free of anthropogenic influences, and (ii) typical urban environment with numerous local sources of carbon dioxide. Despite of relative proximity of those sites (ca. 100 km), substantial differences in both the recorded CO2 levels and their isotopic composition were detected. The CO2 mixing ratios measured in the urban atmosphere revealed quasi-permanent excess concentration of this gas when compared with near-by background atmosphere. The annual mean CO2 concentration recorded in Krakow in 2004 was almost 10% higher than that recorded at high-altitude mountain site (Kasprowy Wierch). Such effect is occuring probably in all urban centers. Carbon isotopic composition of atmospheric CO2 proved to be efficient tool for identification the surface CO2 fluxes into the atmosphere related to fossil fuel burning and their influence on the recorded levels of this gas in the local atmosphere. The available records of ?14C for Krakow and Kasprowy Wierch suggest gradual reduction of 14C-free CO2 fluxes into the urban atmosphere of Krakow in the past several years

Non equilibrium anisotropic excitons in atomically thin ReS2_2

We present a systematic investigation of the electronic properties of bulk and few layer ReS$_2$ van der Waals crystals using low temperature optical spectroscopy. Weak photoluminescence emission is observed from two non-degenerate band edge excitonic transitions separated by $\sim$ 20 meV. The comparable emission intensity of both excitonic transitions is incompatible with a fully thermalized (Boltzmann) distribution of excitons, indicating the hot nature of the emission. While DFT calculations predict bilayer ReS$_2$ to have a direct fundamental band gap, our optical data suggests that the fundamental gap is indirect in all cases

First In human study of a novel biased apelin receptor ligand, MM54, a G-alpha(i) agonist/beta-arrestin antagonist

Introduction: The peptide apelin acts via G proteins to cause beneficial vasodilation and potent positive inotropy to ameliorate pulmonary arterial hypertension in humans and animal models. Apelin is internalised via β-arrestin. In contrast, with loss of endogenous apelin, its receptor acts as a mechanosensor, stimulating β-arrestin to induce detrimental cardiac hypertrophy. Our aim was to characterise the action of our apelin ligand, MM54 that in cell based assays blocks β-arrestin but activates the Gαi protein pathway, in this first in human study. Method: Competition binding in human heart (n=3) used [I125] [Pyr1]apelin-13 (0.1nmol/L). β-arrestin recruitment, receptor internalization and forskolin-induced cAMP inhibition were measured in CHO-K1 cells expressing human apelin receptor. Forearm blood flow was measured in 9 volunteers using venous occlusion plethysmography at baseline and at 4 incremental doses (1, 10, 30, 100 nmol/min) of MM54, each for eight minutes. The Aellig hand vein technique was used to measure the effect of 3 incremental doses (3, 30, 300 nmol/min) of MM54 for 15 min on veins pre-constricted with noradrenaline in 6 individuals compared with 8 controls. Data are mean+SEM, n≥3. Results: MM54 had an affinity of pKi = 6.50±0.03. In β-arrestin (pKB 6.93±0.15) and receptor internalization assays (pKB 5.89±0.06) MM54 was an antagonist, but activated the G protein pathway (pD2±SEM 5.86+0.23). At the highest concentration (100 nmol/min), MM54 caused a significant absolute increase in forearm blood flow compared to control arm, representing a 76 % change from baseline (P<0.01, ANOVA with repeated measures with Dunnett’s post hoc analysis on untransformed data). In the hand vein, MM54 caused a significant concentration dependent dilatation in veins over the concentration range tested, with the highest dose causing 57% reversal (P<0.01). Conclusion: At the cellular level, the results suggest MM54 induced a different conformation in the receptor compared with the native peptide apelin, resulting in a biased profile of activating the G protein pathway but blocking β-arrestin. In agreement in clinical studies, in both the arterial and venous circulation, MM54 induced vasodilatation that is thought to be mediated by the G protein pathway

Effects of Alcohol and Saccharin Deprivations on Concurrent Ethanol and Saccharin Operant Self-Administration by Alcohol-Preferring (P) Rats

Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of EtOH and saccharin (SACC) deprivations on operant oral self-administration. P rats were allowed to lever press concurrently self-administer EtOH (15% v/v) and SACC (0.0125% g/v) for 8 weeks. Rats were then maintained on daily operant access (non-deprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of EtOH daily, or deprived of EtOH and given 2 ml of SACC daily. All groups were then given two weeks of daily operant access to EtOH and SACC, followed by an identical second deprivation period. P rats responded more for EtOH than SACC. All deprived groups increased responding on the EtOH lever, but not on the SACC lever. Daily consumption of 2 ml EtOH decreased the duration of the ADE. Home cage access to 2 ml SACC also decreased the ADE but to a lesser extent than access to EtOH. A second deprivation period further increased and prolonged the expression of an ADE. These results show EtOH is a more salient reinforcer than SACC. With concurrent access to EtOH and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both EtOH and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between EtOH and SACC in their CNS reinforcing effects

Electrical control of orbital and vibrational interlayer coupling in bi- and trilayer 2H-MoS2_2

Manipulating electronic interlayer coupling in layered van der Waals (vdW) materials is essential for designing opto-electronic devices. Here, we control vibrational and electronic interlayer coupling in bi- and trilayer 2H-MoS$_2$ using large external electric fields in a micro-capacitor device. The electric field lifts Raman selection rules and activates phonon modes in excellent agreement with ab-initio calculations. Through polarization resolved photoluminescence spectroscopy in the same device, we observe a strongly tunable valley dichroism with maximum circular polarization degree of $\sim 60\%$ in bilayer and $\sim 35\%$ in trilayer MoS$_2$ that are fully consistent with a rate equation model which includes input from electronic band structure calculations. We identify the highly delocalized electron wave function between the layers close to the high symmetry $Q$ points as the origin of the tunable circular dichroism. Our results demonstrate the possibility of electric field tunable interlayer coupling for controlling emergent spin-valley physics and hybridization driven effects in vdW materials and their heterostructures.Comment: Main manuscript: 10 pages, 4 figures ; Supplemental material: 14 pages, 9 figure

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

Aims - Inhibition of neutral endopeptidases (NEP) results in a beneficial increase in plasma concentrations of natriuretic peptides such as ANP. However NEP inhibitors were ineffective anti-hypertensives, probably because NEP also degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the study was to determine whether SLV-306 (daglutril), a combined ECE/NEP inhibitor, reduced the systemic conversion of big ET-1 to the mature peptide. Secondly, to determine whether plasma ANP levels were increased. Main methods - Following oral administration of three increasing doses of SLV-306 (to reach an average target concentration of 75, 300, 1200 ng ml− 1 of the active metabolite KC-12615), in a randomised, double blinded regime, big ET-1 was infused into thirteen healthy male volunteers. Big ET-1 was administered at a rate of 8 and 12 pmol kg− 1 min− 1 (20 min each). Plasma samples were collected pre, during and post big ET-1 infusion. ET-1, C-terminal fragment (CTF), big ET-1, and atrial natriuretic peptide (ANP) were measured. Key findings - At the two highest concentrations tested, SLV-306 dose dependently attenuated the rise in blood pressure after big ET-1 infusion. There was a significant increase in circulating big ET-1 levels, compared with placebo, indicating that SLV-306 was inhibiting an increasing proportion of endogenous ECE activity. Plasma ANP concentrations also significantly increased, consistent with systemic NEP inhibition. Significance - SLV-306 leads to inhibition of both NEP and ECE in humans. Simultaneous augmentation of ANP and inhibition of ET-1 production is of potential therapeutic benefit in cardiovascular disease

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth