Estimating the phase in ground-based interferometry: performance comparison between single-mode and multimode schemes

In this paper we compare the performance of multi and single-mode interferometry for the estimation of the phase of the complex visibility. We provide a theoretical description of the interferometric signal which enables to derive the phase error in presence of detector, photon and atmospheric noises, for both multi and single-mode cases. We show that, despite the loss of flux occurring when injecting the light in the single-mode component (i.e. single-mode fibers, integrated optics), the spatial filtering properties of such single-mode devices often enable higher performance than multimode concepts. In the high flux regime speckle noise dominated, single-mode interferometry is always more efficient, and its performance is significantly better when the correction provided by adaptive optics becomes poor, by a factor of 2 and more when the Strehl ratio is lower than 10%. In low light level cases (detector noise regime), multimode interferometry reaches better performance, yet the gain never exceeds 20%, which corresponds to the percentage of photon loss due to the injection in the guides. Besides, we demonstrate that single-mode interferometry is also more robust to the turbulence in both cases of fringe tracking and phase referencing, at the exception of narrow field of views (<1 arcsec).Comment: 9 pages (+ 11 online material appendices) -- 8 Figures. Accepted in A&

Simultaneous Determination of Flavonols and Terpene Lactones in Beagle Dog Plasma by Ultra-Performance Liquid Chromatography-Tandem - Mass Spectrometry: 2. Application to Pharmacokinetic Studies on Ginkgo Leaf Extract

Purpose: To evaluate the pharmacokinetics of the major compounds in Ginkgo leaf dosage formulations (namely, Yikangning tablets, Ginaton tablets, Aoshi dropping pills and Yinxinke dispersible tablets), commonly used in traditional Chinese medicine.Methods: A randomized 4*4 crossover study with eight beagle dogs was carried out. Plasma samples were collected following oral administration of four different preparations and the effective ingredients, namely, kaempferol, quercetin, isorhamnetin, ginkgolides A, ginkgolides B, ginkgolides C and bilobalide were detected by a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-TMS). Then the pharmacokinetics of these target compounds, of  different preparations were studied.Results: The adjusted pharmacokinetic data showed that the area under the concentration-time curve from time-zero to the last measurable concentration  (AUC0-t) of kaempferol, quercetin, isorhamnetin, bilobalide, ginkgolides A, ginkgolides B, and ginkgolides C in plasma ranged from 124.37 ± 90.46 to 2261.87 ±  812.35, after administration of Yikangning; 142.28 ± 62.37 to 2529.46 ± 320.48 μg/L•h following administration of Ginaton; 158.52 ± 55.48 to 1987.40 ± 766.21  μg/L•h after Aoshi administration; 160.49 ± 104.66 to 2016.92 ± 1150.92 μg/L•h following Yinxinke administration. The results also indicate that the flavonoids  (especially quercetin) in dispersible tablets and dropping pills hexhibited higher AUC than those in conventional tablets. There were no differences between Aoshi (dropping pills) and Yinxinke (dispersible tablets) in terms of the bioavailability of the flavonoids, but the dropping pill flavonoids showed lower tmax.Conclusion: The results indicate that UPLC-TMS can used to simultaneously evaluate the plasma pharmacokinetics of Ginko compounds in beagle dogsKeywords: Ginkgo biloba, Beagle dog plasma, Kaempferol, Quercetin, Isorhamnetin, Ginkgolides A, Ginkgolides B, Ginkgolides C, Bilobalide, Pharmacokinetics; Bioavailabilit

Simultaneous Determination of Flavonols and Terpene Lactones in Beagle Dog Plasma by Ultra-Performance Liquid Chromatography-Tandem - Mass Spectrometry: 1. Method Development

Purpose: To develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMS/MS) method for the simultaneous determination of 7 major components of Ginkgo leaf (kaempferol, quercetin, isorhamnetin, ginkgolides A, ginkgolides B, ginkgolides C and bilobalide) in dog plasma. Methods: Beagle dog plasma samples were spiked with internal standard (domperidone), acidified with HCl and extracted twice by liquid-liquid extraction using ethyl acetate. Chromatographic separation was achieved on an Acquity UPLC BEH C18 column (100 x 2.1 mm, 1.7 μm) by gradient elution with a run time of 4.0 min. The specificity, linearity, precision, recovery, matrix effect and stability of the method were determined.Results: The method showed high selectivity of the flavonols and terpene lactones in plasma samples. The concentration of the 7 target compounds showed good linear relationship with the peak area ratios of each analyte to internal standard. Lower limit of quantification (LLOQ) was 1.232, 0.240, 0.200, 1.330, 0.960, 0.696, 0.470 ng•mL-1 for kaempferol, quercetin, isorhamnetin, bilobalide, ginkgolides A, ginkgolides B and ginkgolides C, respectively. Recovery of all QC samples ranged from 77.68 to 105.07 %. Matrix effect derived from QC samples was in the range of 85.09 – 113.14 %. The stability of the analytes, calculated as RSD at three  concentrations, was &lt; 15 %.Conclusion: The developed method is simple, rapid and sensitive and can be applied to the determination of kaempferol, quercetin, isorhamnetin, ginkgolides A, ginkgolides B, ginkgolides C and bilobalide in dog plasma.Keywords: Ultra-performance liquid chromatography-tandem mass spectrometry, Ginkgo biloba, Beagle dog plasma, Kaempferol, Quercetin, Isorhamnetin, Ginkgolides A, Ginkgolides B, Ginkgolides C, Bilobalid

Multiple-element exposure and metabolic syndrome in Chinese adults: A case-control study based on the Beijing population health cohort

Background Metabolic syndrome (MetS) patients have a considerably increased risk for noncommunicable diseases, which poses a serious burden on public health. The effects of different elements on MetS have received increasing attention in the field of noncommunicable diseases over the past decade. These elements can exert adverse or favourable effects on human health by synergistic or antagonistic actions. Nevertheless, few studies have explored the relationship between multiple-element exposure and MetS. Method A total of 2095 MetS patients and 2039 controls free of major cardiovascular disease at baseline and follow-up visits were frequency matched for age (±5 years) and sex. The internal exposure levels of 15 elements in serum were investigated. Logistic regression models were employed to estimate odds ratios (ORs) of MetS for element concentrations categorized according to quartiles in the controls. Result Magnesium (Mg), selenium (Se), barium (Ba) and mercury (Hg) were significantly associated with MetS in the multi-element exposure model. The ORs for the extreme quartiles of Mg, Se, Ba, and Hg were 0.29 (95% CI: 0.23–0.37, P-trend < 0.001), 0.52 (95% CI: 0.42–0.65, P-trend < 0.001), 1.86 (95% CI: 1.51–2.28, P-trend < 0.001), and 2.61 (95% CI: 2.11–3.22, P-trend < 0.001), respectively. Ba may be antagonistic to Mg and Se in the human body. Conclusions Our study suggested that MetS was negatively associated with Mg and Se and positively associated with Ba and Hg. There were significant dose-response relationships between Mg, Se, Ba and Hg and the prevalence of MetS, suggesting that multiple elements may be involved in MetS

Serum ApoB levels in depressive patients: associated with cognitive deficits

Cognitive deficits have been regarded as one of the most significant clinical symptoms of depressive disorder. Accumulating evidence has shown that apolipoprotein B (ApoB) levels, which are responsible for inducing neurodegeneration, may be involved in cognitive deficits. This study examines cognitive deficits, and the correlation of serum ApoB levels with cognitive deficits of depressive disorder. 90 depressive patients and 90 healthy controls with matched age and gender were recruited. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum ApoB levels in depressive patients were measured by immunoturbidimetric method. Our results showed that depressive patients had lower scores of cognition including RBANS total score and subscales of language and delayed memory (all, p \u3c 0.001) than healthy controls after controlling for the variables. The differences in cognitive functions also passed Bonferroni corrections. Serum ApoB levels were negatively correlated with delayed memory score in depressive patients (r = −0.30, p = 0.01). Furthermore, stepwise multivariate regression analysis indicated that serum ApoB levels independently contributed to delayed memory in depressive patients (t = −2.68, p = 0.01). Our findings support that serum ApoB levels may be involved in delayed memory decline in depressive patients. Depressive patients also experience greater cognitive deficits, especially in delayed memory and language than healthy controls

mRNA processing in mutant zebrafish lines generated by chemical and CRISPR-mediated mutagenesis produces unexpected transcripts that escape nonsense-mediated decay.

As model organism-based research shifts from forward to reverse genetics approaches, largely due to the ease of genome editing technology, a low frequency of abnormal phenotypes is being observed in lines with mutations predicted to lead to deleterious effects on the encoded protein. In zebrafish, this low frequency is in part explained by compensation by genes of redundant or similar function, often resulting from the additional round of teleost-specific whole genome duplication within vertebrates. Here we offer additional explanations for the low frequency of mutant phenotypes. We analyzed mRNA processing in seven zebrafish lines with mutations expected to disrupt gene function, generated by CRISPR/Cas9 or ENU mutagenesis methods. Five of the seven lines showed evidence of altered mRNA processing: one through a skipped exon that did not lead to a frame shift, one through nonsense-associated splicing that did not lead to a frame shift, and three through the use of cryptic splice sites. These results highlight the need for a methodical analysis of the mRNA produced in mutant lines before making conclusions or embarking on studies that assume loss of function as a result of a given genomic change. Furthermore, recognition of the types of adaptations that can occur may inform the strategies of mutant generation

The influence of the addition of isoprene on the volatility of particles formed from the photo-oxidation of anthropogenic–biogenic mixtures

In this study, we investigate the influence of isoprene on the volatility of secondary organic aerosol (SOA) formed during the photo-oxidation of mixtures of anthropogenic and biogenic precursors. The SOA particle volatility was quantified using two independent experimental techniques (using a thermal denuder and the Filter Inlet for Gas and Aerosols iodide high-resolution time-of-flight Chemical Ionisation Mass Spectrometer – FIGAERO-CIMS) in mixtures of α-pinene/isoprene, o-cresol/isoprene, and α-pinene/o-cresol/isoprene. Single-precursor experiments at various initial concentrations and results from previous α-pinene/o-cresol experiments were used as a reference. The oxidation of isoprene did not result in the formation of detectable SOA particle mass in single-precursor experiments. However, isoprene-derived products were identified in the mixed systems, likely due to the increase in the total absorptive mass. The addition of isoprene resulted in mixture-dependent influence on the SOA particle volatility. Isoprene made no major change to the volatility of α-pinene SOA particles, though changes in the SOA particle composition were observed and the volatility was reasonably predicted based on the additivity. Isoprene addition increased o-cresol SOA particle volatility by ∼5/15 % of the total mass/signal, respectively, indicating a potential to increase the overall volatility that cannot be predicted based on the additivity. The addition of isoprene to the α-pinene/o-cresol system (i.e. α-pinene/o-cresol/isoprene) resulted in slightly fewer volatile particles than those measured in the α-pinene/o-cresol systems. The measured volatility in the α-pinene/o-cresol/isoprene system had an ∼6 % higher low volatile organic compound (LVOC) mass/signal compared to that predicted assuming additivity with a correspondingly lower semi-volatile organic compound (SVOC) fraction. This suggests that any effects that could increase the SOA volatility from the addition of isoprene are likely outweighed by the formation of lower-volatility compounds in more complex anthropogenic–biogenic precursor mixtures. Detailed chemical composition measurements support the measured volatility distribution changes and showed an abundance of unique-to-the-mixture products appearing in all the mixed systems accounting for around 30 %–40 % of the total particle-phase signal. Our results demonstrate that the SOA particle volatility and its prediction can be affected by the interactions of the oxidized products in mixed-precursor systems, and further mechanistic understanding is required to improve their representation in chemical transport models.</p

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses