Intraday Variability Research Articles

Nutrimetric Validation of Solanidine as Dietary-Derived CYP2D6 Activity Marker InVivo.

CYP2D6 is involved in the metabolism of many drugs. Its activity is affected by pharmacogenetic variability leading to highly polymorphic phenotypes between individuals, affecting safety and efficacy of drugs. Recently, solanidine, a steroidal alkaloid from potatoes, and its metabolites, has been identified as a dietary-derived activity marker for CYP2D6. The intraday variability in plasma within individuals has not been studied yet in healthy subjects. As part of a CYP phenotyping cocktail study with 20 healthy participants, plasma concentrations of solanidine, 4-OH-solanidine and 3,4-secosolanidine-3,4-dioic acid (SSDA) were determined using a sensitive liquid chromatography-mass spectrometry method in urine and in plasma at timepoints 0, 2.5, 5, 8, and 24 hours after intake of test substances. The participants were phenotyped for CYP2D6 with oral metoprolol (12.5 mg) with 15 plasma sampling points over 24 hours (DRKS00028922). Metabolic ratios (MRs) of metabolite to parent plasma concentrations were formed from single timepoints and the area under the curve (AUC). All participants were genotyped for CYP2D6. The intra-individual variability of the CYP2D6 metabolite SSDA was highly stable with a median SD of 11.62% over 24 hours. MR SSDA/solanidine was more variable (median SD 31.90%) but correlated significantly at all measured timepoints with AUC MR α-OH-metoprolol/metoprolol. The AUC MR SSDA/solanidine showed a significant linear relationship with the genetically predicted CYP2D6 activity score. This study substantiates the MR SSDA/solanidine as CYP2D6 activity marker. The high correlation with metoprolol MR indicates a valid prediction of the CYP2D6 phenotype at any timepoint during the study day.

Optical intraday variability of the blazar S5 0716+714

ABSTRACT We present an extensive recent multiband optical photometric observations of the blazar S5 0716+714 carried out over 53 nights with two telescopes in India, two in Bulgaria, one in Serbia, and one in Egypt during 2019 November – 2022 December. We collected 1401, 689, 14726, and 165 photometric image frames in B, V, R, and I bands, respectively. We monitored the blazar quasi-simultaneously during three nights in B, V, R, and I bands; four nights in B, V, and R; two nights in V, R, and I; five nights in B and R; and two nights in V and R bands. We also took 37 nights of data only in R band. Single band data are used to study intraday flux variability and two or more bands quasi-simultaneous observations allow us to search for colour variation in the source. We employ the power-enhanced F-test and the nested ANOVA test to search for genuine flux and colour variations in the light curves of the blazar on intraday time-scales. Out of 12, 11, 53, and 5 nights observations, intraday variations with amplitudes between ∼3 and ∼20 per cent are detected in 9, 8, 31 and 3 nights in B, V, R, and I bands, respectively, corresponding to duty cycles of 75, 73, 58, and 60 per cent. These duty cycles are lower than those typically measured at earlier times. On these time-scales colour variations with both bluer-when-brighter and redder-when-brighter are seen, though nights with no measurable colour variation are also present. We briefly discuss possible explanations for this observed intraday variability.

Development of a semi-automated MHC-associated peptide proteomics (MAPPs) method using streptavidin bead-based immunoaffinity capture and nano LC-MS/MS to support immunogenicity risk assessment in drug development.

Major histocompatibility complex (MHC)-Associated Peptide Proteomics (MAPPs) is an ex vivo method used to assess the immunogenicity risk of biotherapeutics. MAPPs can identify potential T-cell epitopes within the biotherapeutic molecule. Using adalimumab treated human monocyte derived dendritic cells (DCs) and a pan anti-HLA-DR antibody (Ab), we systematically automated and optimized biotin/streptavidin (SA)-capture antibody coupling, lysate incubation with capture antibody, as well as the washing and elution steps of a MAPPs method using functionalized magnetic beads and a KingFisher Magnetic Particle processor. Automation of these steps, combined with capturing using biotinylated-Ab/SA magnetic beads rather than covalently bound antibody, improved reproducibility as measured by minimal inter-and intra-day variability, as well as minimal analyst-to-analyst variability. The semi-automated MAPPs workflow improved sensitivity, allowing for a lower number of cells per analysis. The method was assessed using five different biotherapeutics with varying immunogenicity rates ranging from 0.1 to 48% ADA incidence in the clinic. Biotherapeutics with ≥10%immunogenicity incidence consistently presented more peptides (1.8-28 fold) and clusters (10-21 fold) compared to those with <10% immunogenicity incidence. Our semi-automated MAPPs method provided two main advantages over a manual workflow- the robustness and reproducibility affords confidence in the epitopes identified from as few as 5 to 10 donors and the method workflow can be readily adapted to incorporate different capture Abs in addition to anti-HLA-DR. The incorporation of semi-automated MAPPs with biotinylated-Ab/SA bead-based capture in immunogenicity screening strategies allows the generation of more consistent and reliable data, helping to improve immunogenicity prediction capabilities in drug development. MHC associated peptide proteomics (MAPPs), Immunogenicity risk assessment, in vitro/ex vivo, biotherapeutics, Major Histocompatibility Complex Class II (MHC II), LC-MS, Immunoaffinity Capture, streptavidin magnetic beads.

42 Real-time Associations Among MS Symptoms and Cognitive Dysfunction Using Ecological Momentary Assessment

Objective:The current study aimed to examine real-time associations between non-cognitive symptoms and cognitive dysfunction (latter measured both objectively and subjectively in real-time) using ecological momentary assessment (EMA).Participants and Methods:Forty-five persons with MS completed EMA four times per day for three weeks. For each EMA, participants completed mobile versions of the Trail-Making Test part B (mTMT-B) and a finger tapping task, as well as surveys about symptom severity. Trait (usual levels of a symptom) and state (when symptom level was higher or lower than the individual's usual levels) aspects of each symptom's severity were calculated. Multilevel models were conducted to account for within-person clustering, with performance on the mTMT-B and self-reported rating of cognitive dysfunction as primary outcomes.Results:A total of 3,174 EMA sessions were collected; compliance rate was 84%. There was significant intra-day variability in mTMT-B performance, anxiety, fatigue, and pain. More severe state depressive symptoms predicted lower performance on the mTMT-B in real-time. Self-reported difficulties with sleeping the night before predicted mTMT-B performance the following day. In contrast, state (but not trait) fatigue, depression, anxiety, and pain all predicted self-reported cognitive dysfunction in real time. Further, state self-reported cognitive dysfunction (but not mTMT-B performance) was associated with a higher perceived sense of accomplishment.Conclusions:Self-reported cognitive dysfunction was more susceptible to influences of other MS symptoms (especially when the symptom is more severe than the individual's usual levels) and better predicted perceived sense of accomplishment than objectively measured executive functioning in real-time. Objective executive functioning performance was sensitive to effects of depressive symptoms and sleep difficulties. The current study demonstrated the feasibility of assessing real-time associations among MS symptoms using smartphone-administered EMA.

Multiband optical variability on diverse time-scales of the TeV blazar TXS 0506 + 056, the first cosmic neutrino source

ABSTRACT We report the first extensive optical flux and spectral variability study of the TeV blazar TXS 0506 + 056 on intranight to long-term time-scales using BVRI data collected over 220 nights between 2017 January 21 to 2022 April 9 using eight optical ground-based telescopes. In our search for intraday variability (IDV), we have employed two statistical analysis techniques, the nested ANOVA test and the power enhanced F-test. We found the source was variable in 8 nights out of 35 in the R-band and in 2 of 14 in the V-band yielding duty cycles (DC) of 22.8 per cent and 14.3 per cent, respectively. Clear colour variation in V − R was seen in only 1 out of 14 observing nights, but no IDV was found in the more limited B, I, and B − I data. During our monitoring period the source showed a 1.18 mag variation in the R-band and similar variations are clearly seen at all optical wavelengths. We extracted the optical (BVRI) SEDs of the blazar for 44 nights when observations were carried out in all four of those wavebands. The mean spectral index (α) was determined to be 0.897 ± 0.171.

Effect of probenecid on blood levels and renal elimination of furosemide and endogenous compounds in rats: Discovery of putative organic anion transporter biomarkers

Transporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3). However, these metabolites have not been assessed in rats as potential transporter biomarkers. We carried out a rat pharmacokinetic DDI study using probenecid and furosemide as OAT inhibitor and substrate, respectively. Probenecid administration led to a 3.8-fold increase in the blood concentrations and a 3-fold decrease in renal clearance of furosemide. High inter-individual and intra-day variability in pyridoxic acid and kynurenic acid, and no or moderate effect of probenecid administration on these metabolites suggest their limited utility for prediction of Oat-mediated DDI in rats. Therefore, rat blood and urine samples were further analysed using untargeted metabolomics. Twenty-one m/z features (out of >8000 detected features) were identified as putative biomarkers of rat Oat1 and Oat3 using a robust biomarker qualification approach. These m/z features belong to metabolic pathways such as fatty acid analogues, peptides, prostaglandin analogues, bile acid derivatives, flavonoids, phytoconstituents, and steroids, and can be used as a panel to decrease variability caused by processes other than Oats. When validated, these putative biomarkers will be useful in predicting DDIs caused by Oats in rats.

Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition.

The purpose of this study was to present the determination of inter- and intra-day variations in tear flow rate, and tear fluid protein concentration, as well as protein composition regarding their impact for future biomarker studies. Tear fluid was collected noninvasively from 18 healthy subjects by performing Schirmer tests at 4 different time points repetitive in a period of 2days. The tear flow rate on the Schirmer test strips was measured. Proteins were extracted from strips and quantified using amino acid analysis. Protein composition was analyzed by the strips data-independent (DIA) based mass spectrometry. To exclude any impairments to health, volunteers underwent a detailed neurological as well as an ophthalmological examination. Whether tear fluid was collected from oculus sinister or oculus dexter did not affect the tear flow rate (P ≈ 0.63) or protein concentration (P ≈ 0.97) of individual subjects. Moreover, protein concentration was independent from the tear volume, so that a change in volume may only influence the total protein amount. When the examination days were compared, investigation of tear flow rate (P ≈ 0.001) and protein concentration (P ≈ 0.0003) indicated significant differences. Further, mass spectrometric analysis of tear fluid revealed 11 differentially regulated proteins when comparing both examination days. Our findings provide evidence of inter-day variation in tear flow rate, tear proteome concentration, and composition in healthy subjects, suggesting that inter-day variation needs to be taken into consideration in biomarker research of tear fluid. Identified proteins were assigned to functions in the immune response, oxidative and reducing processes, as well as mannose metabolism.

Salting-out assisted liquid–liquid extraction combined with LC–MS/MS for the simultaneous determination of seven organic UV filters in environmental water samples: method development and application

Organic UV filters (OUVFs), the active ingredient in sunscreens, are of environmental concern due to reported ecotoxicological effects in aquatic biota. Determining the environmental concentrations of these chemicals is essential for understanding their fate and potential environmental risk. Salting‐out assisted liquid–liquid extraction (SALLE) coupled with liquid-chromatography tandem mass spectrometry (LC–MS/MS) was developed for simultaneous extraction, separation, and quantification of seven OUVFs (2,4-dihydroxybenzophenone, 2,2′,4,4′-tetrahydroxybenzophenone, 4-methylbenzylidene camphor, butyl-methoxy-dibenzoyl methane, octocrylene, octyl methoxycinnamate, and oxybenzone). Method detection limits (MDLs) ranged from 11 to 45 ng/L and practical quantification limits (PQLs) from 33 to 135 ng/L. Method trueness, evaluated in terms of recovery, was 69–127%. Inter-day and intra-day variability was < 6% RSD. The coefficients of determination were > 0.97. The method was applied to river and seawater samples collected at 19 sites in and near Port Phillip Bay, Australia, and temporal variation in OUVF concentrations was studied at two sites. Concentrations of OUVF were detected at 10 sites; concentrations of individual OUVFs were 51–7968 ng/L, and the maximum total OUVF concentration detected at a site was 8431 ng/L. Recreational activity and water residence time at the site contributed to OUVF’s environmental presence and persistence. The benefits of the SALLE-LC–MS/MS method include its simple operation, good selectivity, precision over a wide linear range, and that obtained extracts can be directly injected into the LC–MS/MS, overall making it an attractive method for the determination of these OUVFs in environmental water matrices. To our knowledge, this is the first report of the occurrence of OUVFs in Port Phillip Bay, Australia.

Long-term X-Ray Outburst in the TeV-detected Blazar Mrk 501 in 2021–2022: Further Clues for the Emission and Unstable Processes

This paper presents the results of a detailed X-ray timing and spectral analysis of Mrk 501, which are based mainly on the Swift data obtained during 2021 February–2022 December. The source showed strongly enhanced X-ray activity, characterized by a long-term increase in the baseline 0.3–10 keV flux level superimposed by shorter-term flares on timescales of a few weeks to about 2 months. During some time intervals, Mrk 501 was the brightest blazar in the X-ray sky and, moreover, showed an intense intraday variability, which was sometimes detected within the exposures lasting a few hundred seconds. These instances were characterized by fractional variability amplitudes of 4%–18% and were mostly observed during short-term X-ray flares. The source exhibited extreme spectral properties with dominance of the spectral curvature, frequent occurrence of hard photon indices in the 0.3–10 keV and 0.3–300 GeV bands, and the peak of a synchrotron spectral energy distribution in the hard X-ray range. These properties demonstrate the importance of relativistic magnetic reconnection, first-order Fermi mechanism within the magnetic field of different confinement efficiencies, stochastic acceleration, and hadronic processes. The X-ray and γ-ray fluxes showed a log-normal distribution, which hints at the imprint of accretion disk instabilities on the blazar jet, as well as the possible presence of hadronic cascades and random fluctuations in the particle acceleration rate. The optical–UV and γ-ray variabilities showed a weak or absent correlation with the X-ray flaring activity, which is not consistent with simple leptonic models and requires more complex particle acceleration, emission, and variability scenarios.

The Quantitative Measurement of Peptidoglycan Components Obtained from Acidic Hydrolysis in Gram-Positive and Gram-Negative Bacteria via Hydrophilic Interaction Liquid Chromatography Coupled with Mass Spectrometry.

The high throughput in genome sequencing and metabolic model (MM) reconstruction has democratised bioinformatics approaches such as flux balance analysis. Fluxes' prediction accuracy greatly relates to the deepness of the MM curation for a specific organism starting from the cell composition. One component is the cell wall, which is a functional barrier (cell shape, exchanges) with the environment. The bacterial cell wall (BCW), including its thickness, structure, and composition, has been extensively studied in Escherichia coli but poorly described for other organisms. The peptidoglycan (PG) layer composing the BCW is usually thinner in Gram- bacteria than in Gram+ bacteria. In both bacteria groups, PG is a polymeric mesh-like structure of amino acids and sugars, including N-acetylglucosamine, N-acetylmuramic acid, and amino acids. In this study, we propose a high-throughput method to characterise and quantify PG in Gram-positive and Gram-negative bacteria using acidic hydrolysis and hydrophilic interaction liquid chromatography coupled with mass spectrometry (HILIC-MS). The method showed a relatively short time frame (11 min analytical run), low inter- and intraday variability (3.2% and 4%, respectively), and high sensitivity and selectivity (limits of quantification in the sub mg/L range). The method was successfully applied on two Gram-negative bacteria (Escherichia coli K12 MG1655, Bacteroides thetaiotaomicron DSM 2079) and one Gram-positive bacterium (Streptococcus salivarius ssp. thermophilus DSM20259). The PG concentration ranged from 1.6% w/w to 14% w/w of the dry cell weight. The results were in good correlation with previously published results. With further development, the PG concentration provided by this newly developed method could reinforce the curation of MM.

Rest-activity disturbances and light exposure in myotonic dystrophy type 1 patients with apathy: An exploratory study using actigraphy

BackgroundRest-activity rhythm disturbances have been reported in myotonic dystrophy type 1 (DM1) but no study has assessed its relationship with apathy and light exposure using actigraphy. MethodsThirty-three DM1 patients wore an actigraph for two consecutive weeks. The Lille Apathy Rating Scale was used to assess apathy. Actigraphy was used to characterize sleep, activity, and light exposure and nonparametric analysis was performed to characterize intraday variability (IV), interday stability (IS), least active five-hour period (L5), most active ten-hour period (M10), and relative amplitude (RA). ResultsApathy was found in 42.4% of patients. Patients with apathy have a larger number of CTG repeat than those without (774 vs 381, p<0.01) Also, patients with apathy had higher IV values (0.98 vs 0.69, p<0.001) as well as lower IS (0.34 vs 0.47, p<0.05), RA (0.65 vs 0.83, p<0.05), and M10 (182.6 vs 493.8, p<0.001) values compared to patients without apathy. In addition, DM1 patients with apathy were exposed to less bright light (≥1000 lux) (41.4 vs 141.2 minutes p<0.01) than patients without. No difference was observed relatively to sleep quality and quantity. ConclusionsDaytime activity levels and bright light exposure were significantly lower in DM1 patients with apathy versus those without. The more fragmented, less stable, and lower amplitude rest-activity rhythm of DM1 patients with apathy, as revealed by non parametric analysis, can be partly ascribed to reduced daylight exposure. The use of bright light therapy as well as physical activity interventions should be explored to help prevent or reduce apathy levels in DM1.

Determination of Flavonoid Compounds in Shanxi Aged Vinegars Based on Hydrophobic Deep Eutectic Solvent VALLME-HPLC Method: Assessment of the Environmental Impact of the Developed Method.

This research presents a novel, eco-friendly, vortex-assisted liquid-liquid microextraction (VALLME) approach, integrating hydrophobic deep eutectic solvents (DESs) with HPLC for the identification and quantification of nine specific flavonoids in Shanxi aged vinegar (SAV). The parameters of DES-VALLME, including the ratio of trioctylmethylammonium chloride to 1,4-butanediol (1:6), DES volume (150 μL), vortex duration (5 min), the concentration of NaCl (0.40 g), and centrifugation time (10 min), were optimized to achieve the maximum extraction efficiency of target substances. Under these optimal conditions, quantitative analyses performed via HPLC demonstrated a broad linear range of 0.20-50.00 μg/mL and correlation coefficients (r2) greater than 0.9944 for all nine calibration curves. The limits of detection (LOD) and limits of quantitation (LOQ) were 0.09-0.18 μg/mL and 0.30-0.60 μg/mL, respectively, ensuring high sensitivity. The relative standard deviations for intra-day and inter-day variability were within the acceptable range, 2.34-3.77% and 3.04-4.96%, respectively, demonstrating the method's reliability. The recovery rates ranged from 85.97% to 108.11%, underscoring the method's precision. This technique exhibited a significant enrichment effect (enrichment factor: 43 to 296) on SAV flavonoids. Notably, the eco-friendliness of this procedure was evaluated using the Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical Greenness Metric. The results suggested that this technique is a viable green alternative to traditional flavonoid determination methods in SAV. In summary, this novel method provides a theoretical basis for assessing flavonoid content in SAV samples and tracing SAV products. This contribution has significant implications for enhancing analytical techniques in food chemistry and environmental science and the sustainable development of the food industry.

A simple and rapid extraction of lipids in plasma using spin column with superabsorbent polymer beads for mass spectrometry

The efficient extraction of lipid species in plasma was developed for quick sample preparation and accurate lipid analysis, using spin column with superabsorbent polymer beads (SAP), as the improvement of previous SAP method reported before. The modified SAP (mSAP) method is composed of simple steps, including sample loading, swelling, solvent addition, centrifugation, and drying of the resulting lipid solution. The mSAP method offers several advantages over the conventional and the previous SAP methods for lipid analysis in plasma sample. The mSAP method was approximately 10 times faster than the modified Folch protocol (Matyash method), methyl-tert-butyl ether based extraction method. The mSAP method offered an excellent recovery rate for most all major classes in the lipid standard mixture, outperforming the Matyash method. The limit of detection (LOD) of 1,2-diheptadecanoyl-sn-glycero-3-phophocholine (PC 17:0/17:0) spiking in plasma by the mSAP method is about seven times lower than those of the conventional methods. The relative standard deviation (RSD) values for inter- and intra-day variability of the mSAP method over a 5-day period were significantly lower than those of the previous SAP and Matyash methods. The mSAP method has been shown to be more time-saving, sensitive, reproducible and reliable, as evidence by its faster processing time, lower LOD, lower RSD values and high recovery rate for different lipid classes. Overall, these findings suggest that this method may be a promising approach for the application of total lipid analysis in lipidomic research in future.

Spatiotemporal variability of extreme temperature indices and their implications over the heterogeneous river basin, India.

The current study on spatiotemporal variability of temperature presents a holistic approach for quantifying the joint space-time variability of extreme temperature indices over the physio-climatically heterogeneous Tapi River basin (TRB) using two unsupervised machine learning algorithms, i.e., principal component analysis (PCA) and cluster analysis. The long-term variability in extreme temperature indices, recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI), was evaluated for 1951-2016. The magnitude and statistical significance of the temporal trend in extreme temperature indices were estimated using non-parametric Sen's slope estimator and modified Mann Kendall (MMK) tests, respectively. The multivariate assessment of temporal trends using PCA resulted in four principal components (PCs) encapsulating more than 90% variability. The cluster analysis of corresponding PCs resulted in two spatial clusters exhibiting homogeneous spatiotemporal variability. Cluster 1 is characterized by significantly increasing hottest, very hot, and extremely hot days with rising average maximum temperature and intraday temperature variability. On the other hand, cluster 2 showed significantly rising coldest nights, mean minimum, mean temperature, and Tx37 with significantly decreasing intraday and interannual temperature variability, very cold, and extremely cold nights with reducing cold spell durations. The summertime heat stress computation revealed that the Purna sub-catchment of the Tapi basin is more vulnerable to various health issues and decreased work performance (> 10%) for more than 45days per year. The current study dealing with the associated effects of rising temperature variability on crop yield, human health, and work performance would help policymakers formulate better planning and management strategies to safeguard society and the environment.

Epoch-Wise Estimation and Analysis of GNSS Receiver DCB under High and Low Solar Activity Conditions

Differential code bias (DCB) is one of the main errors involved in ionospheric total electron content (TEC) retrieval using a global navigation satellite system (GNSS). It is typically assumed to be constant over time. However, this assumption is not always valid because receiver DCBs have long been known to exhibit apparent intraday variations. In this paper, a combined method is introduced to estimate the epoch-wise receiver DCB, which is divided into two parts: the receiver DCB at the initial epoch and its change with respect to the initial value. In the study, this method was proved feasible by subsequent experiments and was applied to analyze the possible reason for the intraday receiver DCB characteristics of 200 International GNSS Service (IGS) stations in 2014 (high solar activity) and 2017 (low solar activity). The results show that the proportion of intraday receiver DCB stability less than 1 ns increased from 72.5% in 2014 to 87% in 2017, mainly owing to the replacement of the receiver hardware in stations. Meanwhile, the intraday receiver DCB estimates in summer generally exhibited more instability than those in other seasons. Although more than 90% of the stations maintained an intraday receiver DCB stability within 2 ns, substantial variations with a peak-to-peak range of 5.78 ns were detected for certain stations, yielding an impact of almost 13.84 TECU on the TEC estimates. Moreover, the intraday variability of the receiver DCBs is related to the receiver environment temperature. Their correlation coefficient (greater than 0.5 in our analyzed case) increases with the temperature. By contrast, the receiver firmware version does not exert a great impact on the intraday variation characteristics of the receiver DCB in this case.

More complex than you think: Taxonomic and temporal patterns of plant-pollinator networks of caraway (Carum carvi L.).

Caraway (Carum carvi L.) is a crop species that is gaining in importance in Europe, especially as a condiment and medicinal plant. Here, we present the plant-pollinator network of caraway in a central European agricultural landscape, focusing on two diverse potential pollinator taxa, Diptera: Brachycera (= true flies) and Hymenoptera (sawflies, bees, and wasps). We specifically studied qualitative differences in interactions between the two insect taxa as well as the intraday and intraseasonal variability of the network. Insect and pollen plant species determination was done via morphological identification and DNA (meta)barcoding. In total, 121 species representing 33 families of Hymenoptera and Brachycera were found to carry caraway pollen. These taxa included many nonhoneybee and nonhoverfly species, showing a wide taxonomic breadth of potential pollinators and a higher network complexity than previously anticipated. There are distinct qualitative differences between Brachycera and Hymenoptera networks, suggesting complementary roles of both taxa in the pollination of native and crop plants. Strong intraday differences in potential pollinator diversity make it necessary to collect insects and pollen at different times of the day to compile complete plant-pollinator networks. Intraseasonal analyses of the plant-pollinator network of caraway show the potential of caraway as an important food source for insect species with an activity peak in late summer.

A new method to separate the impacts of interday and intraday temperature variability on mortality

BackgroundTemperature variability (TV) is associated with increased mortality risks. However, the independent impacts of interday and intraday are still unknown.MethodsWe proposed a new method to decompose TV into interday TV and intraday TV through algebra derivation. Intraday TV was defined as the weighted average standard deviation (SD) of minimum temperature and maximum temperature on each day. Interday TV was defined as the weighted SD of daily mean temperatures during the exposure period. We then performed an illustrative analysis using data on daily mortality and temperature in France in 2019–2021.ResultsThe novel interday and intraday TV indices were good proxies for existing indicators, inlcluding diurnal temperature range (DTR) and temperature change between neighbouring days (TCN). In the illustrative analyses, interday and intraday TVs showed differentiated mortality risks. Mortality burden related to TV was mainly explained by the intraday component, accounting for an attributable fraction (AF) of 1.81% (95% CI: 0.64%, 2.97%) of total mortality, more than twice the AF of interday TV (0.86%, 95% CI: 0.47%, 1.24%).ConclusionsThis study proposed a novel method for identifying and isolating the different components of temperature variability and offered a comprehensive way to investigate their health impacts.

The optical behaviour of BL Lacertae at its maximum brightness levels: a blend of geometry and energetics

ABSTRACT In 2021 BL Lacertae underwent an extraordinary activity phase, which was intensively followed by the Whole Earth Blazar Telescope (WEBT) Collaboration. We present the WEBT optical data in the BVRI bands acquired at 36 observatories around the world. In mid-2021 the source showed its historical maximum, with R = 11.14. The light curves display many episodes of intraday variability, whose amplitude increases with source brightness, in agreement with a geometrical interpretation of the long-term flux behaviour. This is also supported by the long-term spectral variability, with an almost achromatic trend with brightness. In contrast, short-term variations are found to be strongly chromatic and are ascribed to energetic processes in the jet. We also analyse the optical polarimetric behaviour, finding evidence of a strong correlation between the intrinsic fast variations in flux density and those in polarization degree, with a time delay of about 13 h. This suggests a common physical origin. The overall behaviour of the source can be interpreted as the result of two mechanisms: variability on time-scales greater than several days is likely produced by orientation effects, while either shock waves propagating in the jet, or magnetic reconnection, possibly induced by kink instabilities in the jet, can explain variability on shorter time-scales. The latter scenario could also account for the appearance of quasi-periodic oscillations, with periods from a few days to a few hours, during outbursts, when the jet is more closely aligned with our line of sight and the time-scales are shortened by relativistic effects.

Study of Variability in Long-term Multiwavelength Optical Lightcurves of Blazar AO 0235+164

We present a long-term and intraday variability study of optical multiwaveband (U BV RI) data from the blazar AO 0235+164 collected by various telescopes for ∼44 yr (1975–2019). The blazar was found to be significantly variable over the years in all wave bands with a variation of about 6 mag between its low and active states. The variations in the different wave bands are highly correlated without any time lag. We did not observe any significant trend in color variation with time, but we observed a bluer-when-brighter trend between the B − I color index and the R magnitude. Optical BV R-band spectral energy distributions always show a convex shape. Significant intraday variability was frequently seen in the quasi-simultaneous observations of AO 0235+164 made on 22 nights in the R and V bands by the CASLEO and CAHA telescopes during 1999–2019. We also estimated a central supermassive black hole mass of 7.9 × 107 M ⊙ by analyzing the broad Mg ii emission line in AO 0235+164's spectrum. We briefly explore the probable physical scenarios responsible for the observed variability.

Analysis of Furan and Its Derivatives in Food Matrices Using Solid Phase Extraction Coupled with Gas Chromatography-Tandem Mass Spectrometry.

The objective of this study was to develop a simultaneous analysis method of furan and its 10 derivatives in different food commodities. The results indicated that furan and its 10 derivatives could be separated within 9.5 min by using a HP-5MS column and gas chromatography-tandem mass spectrometry (GC-MS/MS) with multiple reaction monitoring mode for detection. Furthermore, this method could resolve several furan isomers, such as 2-methyl furan and 3-methyl furan, as well as 2,3-dimethyl furan and 2,5-dimethyl furan. The most optimal extraction conditions were: 5 g of the fruit or juice sample mixed with 5 mL of the saturated NaCl solution, separately, or 1 g of the canned oily fish sample mixed with 9 mL of the saturated NaCl solution, followed by the equilibration of each sample at 35 °C for 15 min, using a carboxen-polydimethylsiloxane SPME arrow to adsorb the analytes for 15 min at 35 °C for subsequent analysis by GC-MS/MS. For method validation of all the analytes in the different food matrices, the recovery was 76-117% and the limit of the quantitation was 0.003-0.675 ng/g, while the relative standard deviation (RSD%) of the intra-day variability range from 1-16%, and that of the inter-day variability was from 4-20%. The method validation data further demonstrated that a reliable method was established for the analysis of furan and its 10 derivatives in commercial foods.