Intraday Variability Research Articles

Development of a deep eutectic solvent-based matrix solid phase dispersion methodology for the determination of aflatoxins in crops

A novel and sensitive deep eutectic solvent-based matrix solid phase dispersion (DES-MSPD) method for the determination of aflatoxins (AFB1, AFB2, AFG1, AFG2) in various crops was established using high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The DES-MSPD sample preparation procedure was optimized. Based on the optimal conditions, the intra-day and inter-day variability for AFs in all crop samples was less than 7.5%. Linearity was observed with R2 values (>0.994). Using the present method, HPLC-FLD gave the limits of detection (LODs) of 0.03–0.10 μg/kg and the limits of quantification (LOQs) of 0.10–0.33 μg/kg for AFs. This work represents the first attempt of using DESs as a green extraction medium for the extraction of AFs in MSPD. Compared with conventional MSPD methods, the DES-MSPD procedure looks promising as a relatively simple and low cost process to build an assay that can be used for monitoring concentrations of AFs in crops.

The effect of variable renewable energy sources on electricity price volatility: the case of the Iberian market

ABSTRACTThe relationship between variable renewable energy supply (V-RES) and electricity price volatility is a controversial issue in the economic literature. In general, the literature has been inconclusive about the sign of the impact of installed capacity of these technologies on price volatility. This paper investigates the impact of V-RES on price volatility for the Iberian Market of Electricity (MIBEL), in the period ranging from 2010 to 2015. Using regression analysis and EGARCH models, we conclude that V-RES, and more specifically wind power supply, heightens price volatility. Likewise, greater intraday variability of V-RES also induces higher price volatility. Finally, following an analysis of the connection with the French market, we find that market coupling could help alleviate the sensitivity of price volatility to wind power supply variability.

Simulating phytoplankton growth during the spring thermal bar in a deep lake

Phytoplankton growth in Lake Baikal was simulated during thermal bar events using meteorological data from June 1–30, 2017. Dynamics of the thermal bar and the plankton population were reproduced by the coupled physical–biological model that describes hydrodynamic processes and interactions of the components of the nutrient–phytoplankton–zooplankton–detritus system. The key point of the model is consideration of atmospheric impact on the lake surface, taking into account the intraday variability of wind forcing and fluxes of shortwave and longwave radiation and latent and sensible heat. Numerical modeling showed that a combination of cabbeling instability, associated with the thermal bar, and wind-driven currents lead to sinking of the phytoplankton biomass from the surface area to the lower layers of the lake. The increase in phytoplankton results in a degradation of the nutrients in the corresponding water environment. Simulations demonstrated that the maximum concentrations of phytoplankton are localized in the inshore side of the thermal bar. At the same time, the thermal bar acted as a barrier preventing the horizontal propagation of the biological substances into open waters. A comparative analysis of the calculated temperature and phytoplankton distributions with available field data was performed. • Plankton dynamics during the spring thermal bar in a deep lake were simulated. • The thermal bar acts as a barrier to horizontal propagation of the plankton biomass. • Wind forcing plays a significant role in the time-space distribution of the phytoplankton. • Wind contributes to sinking of the phytoplankton to the lower layers of the lake.

Variability of the Blazar J1504+1029 on Timescales from Hours to Years

The results of observations of the blazar J1504+1029 (PKS 1502+106, OR 103), obtained in 2000–2018 on the RATAN-600 radio telescope of the Special Astrophysical Observatory at 2.3, 3.9 (4.7), 7.7 (8.2), 11.2, and 21.7 GHz and on the 32-m Zelenchuk and Badary radio telescopes of the Quasar-KVO complex of the Institute of Applied Astronomy of the Russian Academy of Sciences at 5.05 and 8.63 GHz are presented. The long-term variability is studied, as well as variability on time scales from several days to several weeks and intraday variability (IDV). The long-term light curves are correlated at all frequencies and show continuous activity, against which three flares with their maxima in 2002, 2009, and 2018 are distinguished. The time scale for variability of the flare in 2009 is τvar ≈ 1 year. At 21.7 GHz, the linear size of the emitting region is R ≤ 0.3 pc, its angular size is θ ≤ 0.05 mas, its brightness temperature is Tb ≥ 2 × 1014 K, and the Doppler factor is δ ≥ 5.8. The flare with its maximum in 2018 has a long rising branch at 21.7 GHz: τvar = 3.2 years, linear size R ≤ 1.1 pc, angular size θ ≤ 0.17 μas, brightness temperature Tb ≥ 2.2 × 1012 K, and Doppler factor δ ≥ 2.8. Among eleven sets of daily observations of the source over 75–120 days in 2000–2017, variability was detected in eight data sets at two to four frequencies with characteristic time scales of 4–30 days. In seven data sets, the variability is due to one to three cyclic processes with characteristic time scales τacf = 4−30d. The spectral indices of the variable components in different years vary from αvar = −1.6 to +1.8. In at least four data sets, the variability is due to processes in the source itself. In this case, at 21.7 GHz, the apparent linear size of the emitting region is ≤4000 AU, the angular size is θ ≤ 3.5 μas, the brightness temperature is Tb ≥ 3 × 1014 K, and the Doppler factor is δ ≥ 14. In the 2004 data set, the variability has an “ anti-flare” form, with the flux density of the variable component falling at high frequencies. Thirty-six successful sessions were conducted on the 32-m telescopes at 8.63 GHz, and 16 at 5.05 GHz. IDV was detected in 17 sessions at 8.63 GHz and in three sessions at 5.05 GHz, with the IDV being detected mainly near flare maxima.

Evaluation of liver and spleen stiffness of healthy dogs by use of two-dimensional shear wave elastography

To assess liver and spleen stiffness in healthy dogs by use of a novel 2-D shear wave elastography (SWE) technique and to investigate the repeatability and reproducibility of the technique. 8 healthy adult Beagles. 2-D SWE was performed on each dog to assess liver and spleen stiffness. Repeatability (intraday variability) and reproducibility (interday variability) of 2-D SWE were investigated. For all 8 dogs, 2-D SWE was performed 3 times in 1 day (4-hour intervals) and on 3 separate days (1-week interval). Data were expressed as mean ± SD values for shear wave velocity and the Young modulus in the liver and spleen. Intraday and interday coefficients of variation were assessed for all variables. Mean ± SD shear wave velocity obtained for the liver and spleen was 1.51 ± 0.08 m/s and 2.18 ± 0.27 m/s, respectively. Mean value for the Young modulus obtained for the liver and spleen was 6.93 ± 0.79 kPa and 14.66 ± 3.79 kPa, respectively. Elasticity values were significantly higher for the spleen than for the liver. Intraday and interday coefficients of variation for all variables were < 25% (range, 3.90% to 20.70%). 2-D SWE was a feasible technique for assessing liver and spleen stiffness of healthy dogs. Future studies on the application of 2-D SWE for dogs with chronic hepatitis, cirrhosis, and portal hypertension are needed to evaluate the clinical applicability of 2-D SWE.

Multiple models for artificial pancreas predictions identified from free-living condition data: A proof of concept study

The artificial pancreas (AP) is a closed-loop system to automatically regulate the glucose concentration in patients with type 1 diabetes (T1D). Model predictive control (MPC) revealed to be one of the most promising approaches for this control problem. Several MPC algorithms have been tested in clinical trials with satisfactorily results. However, the inter-patient variability characterising T1D patients limits the performance of MPC algorithms synthesized on average models and calls for patient-tailored models. The availability of experimental data on long outpatient trials motivated the study of identification techniques applicable to free-living patient data. Moreover, a detailed data analysis can be used to improve model identification. Considered that the postprandial (PP) glucose control is one of the most critical aspects of glucose regulation, the analysis was focused on the PP period. The intra-day variability is investigated via ANOVA test that highlighted a correlation between PP glucose profiles and different day periods (DPs). A data-driven multiple-model predictor (MMP) based on real-data analysis is proposed in this work. It exploits different identified models on the basis of the knowledge acquired through the data analysis. In particular, the MMP uses three basic models specific of each DP. These models have been identified through the impulse-response technique that achieved promising results in model identification from real-data. The prediction capabilities of the MMP are compared to the performance of a predictor built using a single model identified on a daily subset, showing an improvement in terms of predictions capabilities in the breakfast DP.

Evaluation of prenylflavonoids and hop bitter acids in surplus yeast.

This study developed a high performance liquid chromatography with diode array detection (HPLC-DAD) and tandem mass spectrometry (MS-MS) method for determination of prenylflavonoids and hop bitter acids in surplus yeast, a byproduct from beer brewing process. This method enabled the simultaneous separation of 4 prenylflavonoids and 20 hop bitter acids within 30min by employing a Hypersil-Keystone HyPURITY C18 column and a gradient mobile phase composed of phosphoric acid aqueous solution at pH 1.6 and acetonitrile. For HPLC-DAD analysis, the limits of detection and limits of quantitation ranged from 0.04 to 0.15µg/mL and from 0.12 to 0.45µg/mL, respectively, and the recoveries ranged from 82.6 to 99.7%. The intra-day variability and inter-day variability ranged from 1.37 to 8.82% and from 0.68 to 9.74%, respectively. For qualitation by MS-MS, the positive mode was discovered to possess satisfactory collision capacity and high sensitivity for prenylflavonoids, while the negative mode was more suitable for the ionization of hop bitter acids. The content of hop bitter acids in surplus yeast were higher than that of prenylflavonoids, and isomers and oxidation products of hop bitter acids were found. This study has advantages in identifying more components, short separation time, satisfactory resolution, high accuracy and high precision.

Metal-organic framework-monolith composite-based in-tube solid phase microextraction on-line coupled to high-performance liquid chromatography-fluorescence detection for the highly sensitive monitoring of fluoroquinolones in water and food samples

In this study, a new metal-organic framework-monolith composite for in-tube solid phase microextraction phase (IT-SPME) of fluoroquinolones (FQs) was prepared. 4-Vinylbenzoic acid was copolymerized with ethylenedimethacrylate in a fused silica capillary to form porous monolith. After that, zeolitic imidazolate frameworks (ZIF-8) were synthesized in situ within the pores and the surface of the monolith by controlled layer-by-layer self-assembly of Zn2+ and imidazole. The introduction of ZIF-8 enhanced the surface area of monolith composite, and thus, improving the extraction performance of IT-SPME for FQs obviously. Under the optimized conditions, a highly sensitive method for the monitoring of FQs residue in water and honey samples was developed by the on-line combination of IT-SPME with high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The limits of detection (S/N = 3) for the targeted FQs in water and honey samples were as low as 0.14–0.61 ng/L and 0.39–1.1 ng/L, respectively. The relative standard deviations (RSDs) for intra-day and inter-day assay variability were less than 10% in all samples. The established on-line IT-SPME-HPLC-FLD was successfully used to detect ultra-trace FQs in environmental water and honey samples. Recoveries at different spiked concentrations ranged from 80.1% to 119% and 80.2–117% for water and honey samples, respectively, with satisfactory reproducibility. Compared to up-to-date reported methods, the proposed approach exhibits some features such as high sensitivity, convenience, partial automation, low consumptions of sample and solvent.

Characterizing Optical Variability of OJ 287 in 2016–2017

Abstract We report on a recent multiband optical photometric and polarimetric observational campaign of the blazar OJ 287 that was carried out during 2016 September–2017 December. We employed nine telescopes in Bulgaria, China, Georgia, Japan, Serbia, Spain, and the United States. We collected over 1800 photometric image frames in BVRI bands and over 100 polarimetric measurements over ∼175 nights. In 11 nights with many quasi-simultaneous multiband (V, R, I) observations, we did not detect any genuine intraday variability in flux or color. On longer timescales, multiple flaring events were seen. Large changes in color with respect to time and in a color–magnitude diagram were seen, and while only a weak systematic variability trend was noticed in color with respect to time, the color–magnitude diagram shows a bluer-when-brighter trend. Large changes in the degree of polarization and substantial swings in the polarization angle were detected. The fractional Stokes parameters of the polarization showed a systematic trend with time in the beginning of these observations, followed by chaotic changes and then an apparently systematic variation at the end. These polarization changes coincide with the detection and duration of the source at very high energies as seen by VERITAS. The spectral index shows a systematic variation with time and V-band magnitude. We briefly discuss possible physical mechanisms that could explain the observed flux, color, polarization, and spectral variability.

Assessment of the utility of X-ray Fluorescence for the chemical characterization and comparison of black electrical tape backings

Elemental analysis of electrical tapes is typically conducted by Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS), although Laser Ablation-Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) recently showed to enhance the sensitivity of the determinations. In this study, the utility of X-ray Fluorescence (XRF) is compared to previously published SEM-EDS and LA-ICP-MS data. Three XRF systems were used to evaluate a range of configurations commonly available at crime laboratories. A set of 40 electrical tape backings known to originate from difference sources was used to assess the inter-roll variability, discrimination and classification capabilities of the method. The discrimination for this tape set increased from 78.8% achieved by SEM-EDS to 81.5–91.0% by XRF, depending on the instrumental configuration. In comparison, LA-ICP-MS achieved 84.6% discrimination on these tapes. The overall characterization, classification, and discrimination capabilities for this set improved as follows: SEM-EDS < iXRF < small spot size benchtop XRF with SDD, LA-ICP-MS < large spot size XRF. A set of 20 pieces of tapes collected from the same roll were analyzed for intra-roll variability. Duplicate control same-source samples were used to evaluate inter-day and intra-day instrument variability. No false exclusions were observed in the data set, demonstrating the within-sample variability and instrumental variability are relatively lower than the inter-sample variability. One concern of the method is the penetration depth of the X-ray beam beyond the target backing, requiring careful sample preparation to avoid interference from the adhesive or sample holder. XRF is a viable analytical tool for the forensic examination of electrical tapes, with advantages of speed of analysis, minimal destruction of the tape, and high informing power.

The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia.

Impaired glucose metabolism is associated with an increased risk of cardiovascular complications, and coronary artery spasm is thought to underlie the development of coronary artery disease. Intraday glucose variability (GV) accelerates oxidative stress and inflammatory cytokine release, but its impact on coronary artery spasm remains unclear. This study investigated the relationship between intraday GV and coronary artery spasm. The study included 50 patients with dysglycemia and suspected coronary spastic angina. GV was analyzed by 24-h monitoring of the blood glucose concentration using a flash glucose monitoring system. The mean amplitude of glycemic excursion (MAGE) was calculated as an index of GV. Coronary artery spasm was assessed using the intracoronary acetylcholine provocation test. Coronary spasm was defined as acetylcholine-induced total or subtotal coronary occlusion. Changes in vessel diameter in response to acetylcholine were evaluated with quantitative coronary angiography. Coronary artery spasms were observed in 21 patients (42%). MAGE was significantly higher in patients with spasms compared to those without spasms (127.5 ± 33.5 vs. 91.4 ± 37.6, p < 0.01). Regression analysis showed a positive correlation between MAGE levels and coronary diameter changes induced by acetylcholine (r = 0.47, p < 0.01). In multiple regression analysis, MAGE was independently associated with acetylcholine-induced coronary diameter change (β = 0.47, p < 0.01). Intraday GV was associated with coronary artery spasm in patients with dysglycemia.

Glycemic variability as a predictor of major adverse cardiac events after percutaneous coronary intervention

Background: The endothelial dysfunction was greater by glucose fluctuation than by chronic hyperglycemia. The glycemic variability (GV) may be an independent risk factor for atherosclerotic coronary artery disease in diabetic patients. The cardiovascular complications are higher following myocardial infarction in diabetic patients than nondiabetic individuals. Aim of the Work: Our aim is to prove that good controlling of acute shooting of blood glucose level up and down will improve the outcome in patient undergoing percutaneous coronary intervention (PCI). Subjects and Methods: GV is evaluated using intraday variability by fasting, preprandial, and postprandial blood glucose levels in 120 patients. Hemoglobin A1c was used to evaluate glycemic control. The relationship between GV and development of major adverse cardiac events (MACE) in patients undergoing PCI is studied. Results: There is a statistically significant difference between the relation of GV and MACE within 1 month after PCI in uncontrolled diabetes compared to controlled group. There is no statistically significant difference found between the two groups regarding age, gender, risk factors (hypertension, smoking and dyslipidemia), and laboratory parameters including triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein. Conclusions: Uncontrolled GV is associated with poor short-term outcome after PCI in controlled diabetic patients compared to nondiabetic individuals undergoing PCI. Greater GV is associated with composite MACE, especially for uncontrolled diabetic patients. After multivariable logistic analysis, GV remains an independent prognostic factor for composite MACE after 3 months in patients undergoing PCI.

Preliminary assessment of two spatio-temporal forecasting technics for hourly satellite-derived irradiance in a complex meteorological context

This paper examines two spatio-temporal approaches for short-term forecasting of global horizontal irradiance using gridded satellite-derived irradiances as experimental support. The first approach is a spatio-temporal vector autoregressive (STVAR) model combined with a statistical process for optimum selection of input variables. The second is an existing operational cloud motion vector (CMV) model. An evaluation of the predictive performance of these models is presented for a case study area in the Caribbean Islands. This region is characterized by a large diversity of microclimates and land/sea contrasts, creating a challenging solar forecasting context. Using scaled persistence as a reference, we benchmark the performance of the two spatio-temporal models over an extended 220 × 220 km domain, and for three specific, climatically distinct locations within this domain. We also assess the influence of intra-day solar resource variability on model performance. Finally, we present preliminary evidence that a blend of CMV and STVAR forecasts leads to improved accuracy under all conditions.

Simplified LC/MS assay for the measurement of isolevuglandin protein adducts in plasma and tissue samples

Isolevuglandins (IsoLGs) are a family of highly reactive 4-ketoaldehydes formed by lipid peroxidation that modify the lysyl residues of cellular proteins. Modification of proteins by IsoLGs have been shown to contribute to disease processes such as the development of hypertension. Accurate quantitation of the extent of protein modification by IsoLGs is essential for understanding the mechanisms whereby these modifications contribute to disease and the efficacy of interventions designed to prevent this modification. The previously described LC/MS assay to quantitate IsoLG protein adducts was extremely labor-intensive and time consuming, and while it offered reasonably low intra-day variation for replicate samples, variation when replicate samples were processed on separate days was significant. These limitations significantly restricted utilization of this approach. We therefore performed a series of studies to optimize the assay. We now report a significantly simplified LC/MS assay for measurement of IsoLG protein adducts with increased sensitivity and lower intra-day and inter-day variability.

Effects of Insulin Degludec and Insulin Glargine U300 on Day-to-Day Fasting Plasma Glucose Variability in Individuals with Type 1 Diabetes: A Multicenter, Randomized, Crossover Study (Kobe Best Basal Insulin Study 2).

IntroductionAdministered basal insulin markedly influences the fasting plasma glucose (FPG) level of individuals with type 1 diabetes. Insulin degludec (IDeg) and insulin glargine U300 (IGlar U300) are now available as ultra-long-acting insulin formulations, but whether or how their glucose-stabilizing effects differ remains unclear. We will compare the effects of these basal insulins on parameters related to blood glucose control, with a focus on day-to-day glycemic variability, in individuals with type 1 diabetes treated with multiple daily injections.MethodsA multicenter, randomized, open-label, crossover, comparative study (Kobe Best Basal Insulin Study 2) will be performed at 13 participating institutions in Japan. A total of 46 C-peptide-negative adult outpatients with type 1 diabetes will be randomly assigned 1:1 by a centralized allocation process to IGlar U300 (first period)/IDeg (second period) or IDeg (first period)/IGlar U300 (second period) groups, in which subjects will be treated with the corresponding basal insulin for consecutive 4-week periods. The basal insulin will be titrated to achieve an FPG of less than 130 mg/dL initially and then less than 110 mg/dL if feasible. In the last week of each period, plasma glucose will be determined seven times a day by self-monitoring of blood glucose (SMBG) and intraday and day-to-day glucose excursions will be determined by flash glucose monitoring (FGM). The primary end point is comparison of day-to-day glycemic variability as evaluated by the standard deviation (SD) of FPG during the last week of each treatment period. Secondary end points include the coefficient of variance of FPG, the frequency of severe hypoglycemia as evaluated by SMBG, the duration of hypoglycemia as evaluated by FGM, intraday glycemic variability calculated from both SMBG and FGM data, and the administered insulin dose.Planned OutcomesThe results of the study will be submitted for publication in a peer-reviewed journal to report differences in the effects of two ultra-long-acting basal insulins, IDeg and IGlar U300.ConclusionThis head-to-head comparison will be the first study to compare the effects of IDeg and IGlar U300 on day-to-day FPG variability in C-peptide-negative individuals with type 1 diabetes.Trial RegistrationRegistered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry as 000029630 on 20 June 2017.FundingNovo Nordisk Pharma Ltd.

X-ray Intraday Variability of the TeV Blazar Mrk 421 with Chandra

We present an extensive study of 72 archival Chandra light curves of the high-frequency-peaked type blazar Mrk 421, the first strong extragalactic object to be detected at TeV energies. Between 2000 and 2015 Mrk 421 often displayed intraday variability in the 0.3-10.0 keV energy range, as quantified through fractional variability amplitudes that range up to 21.3 per cent. A variability duty cycle of ~84 per cent is present in these data. Variability timescales, with values ranging from 5.5 to 30.5 ks, appear to be present in seven of these observations. Discrete correlation function analyses show positive correlations between the soft (0.3-2.0 keV) and hard (2.0-10.0 keV) X-ray energy bands with zero time lags, indicating that very similar electron populations are responsible for the emission of all the X-rays observed by Chandra. The hardness ratios of this X-ray emission indicate a general "harder-when-brighter" trend in the spectral behaviour of Mrk 421. Spectral index-flux plots provide model independent indications of the spectral evolution of the source and information on the X-ray emission mechanisms. Brief discussions of theoretical models that are consistent with these observations are given.

Multi-color Optical Monitoring of 10 Blazars from 2005 to 2011

We carried out multi-color optical monitoring of a sample of ten blazars from 2005 to 2011. The sample contains 3 LBLs, 2 IBLs, 4 HBLs, and 1 FSRQ. Our monitoring focused on the long-term variability and the sample included nine BL Lac objects and one flat-spectrum radio quasar. A total number of 14799 data points were collected. This is one of the largest optical database for a sample of ten blazars. All objects showed significant variability except OT 546. Because of the low sampling on each single night, only BL Lacertae was observed to have intra-day variability on 2006 November 6. Most BL Lac objects showed a bluer-when-brighter chromatism, while the flat-spectrum radio quasar, 3C 454.3, displayed a redder-when-brighter trend. The BWB color behaviors of most BL Lacs can be at least partly interpreted by the fact of increasing variation amplitude with increasing frequency observed in these objects. The average spectral index of LBLs is around 1.5, as expected from the model dominated by Synchrotron Self-Compton (SSC) loss. The optical emission of HBL is probably contaminated by the thermal emission from the host galaxies. Correlation analysis did not reveal any time delay between variations at different wavelengths.

Intraday Mid-infrared Variability of CTA 102 During Its 2016 Giant Outburst

Abstract We report the discovery in archival data from Wide-field Infrared Survey Explorer (WISE) of intraday mid-infrared (mid-IR) variability of CTA 102 during its 2016 giant outburst. The mid-IR emission of CTA 102 reached its peak around 2016 November and exhibited prominent minor flares within one day. Mid-IR color shows a bluer-when-brighter trend like the optical band during the flaring period. These characteristics likely suggest that CTA 102 was experiencing a transition from flat-spectrum radio quasar to BL Lac, whose synchrotron emission from the relativistic jet was then boosted to totally dominate optical and infrared emission.

Focus Meeting #3: Radio Galaxies – Resolving the AGN Phenomenon

In this presentation, we report the results of intraday variability in the optical (BVRI bands) and hard X-ray band (3-79 keV) in a number of blazars. In the optical microvariability studies of the blazars S5 0716+714 and BL Lac, we observed many interesting features such as rapid variability, large variability amplitude, presence of characteristic timescales, bluer-when-brighter achromatic behavior, and single power-law power spectral density. In {\it NuSTAR} observations of several blazars, using spectral and timing analysis, we found similar features consistent with the optical studies. In addition, in BL Lacs we estimated the Lorentz factor of the population of highest energy electrons emitting synchrotron emission, and whereas in flat-spectrum radio quasars, using external Compton models, we estimated the energy of the lower end of the injected electrons to be a few tens of Lorentz factors. In addition, we find that the low flux state exhibit more rapid variability in contrast to the previously reported results showing high flux states displaying rapid variability. In both the studies, the size of the emission regions estimated using variability timescales turn out to be an order magnitude smaller than the gravitational radius of a typical black-hole masses between $\sim 10^8-10^9$ solar masses, believed to be at the center of the radio-loud AGN. The results of the studies suggest that these low-amplitude rapid variability might originate as a result of magnetohydrodynamical instabilities near the base of the jets triggered by the processes modulated by the magnetic field at accretion disc.

Simultaneous quantification of urinary 6‑sulfatoxymelatonin and 8‑hydroxy‑2′‑deoxyguanosine using liquid chromatography-tandem mass spectrometry

Oxidative stress is involved in the pathophysiology of many diseases and natural aging. Urinary 8‑hydroxy‑2′‑deoxyguanosine (8‑OHdG), a stable product of DNA oxidative damage, has been widely used as an oxidative stress biomarker. However, only reporting 8‑OHdG level, as commonly done previously, does not take into account of damaged DNA molecules that have not been repaired and excreted in urine. Melatonin is known to help with DNA repairs and hence can modify 8‑OHdG levels. 6‑sulfatoxymelatonin (aMT6s) is a major metabolite of melatonin excreted in urine. Hence it is useful to measure both urinary 8‑OHdG and aMT6s together. Here we describe a newly developed and validated method to simultaneously measure these two compounds using high-performance liquid chromatography-tandem mass spectrometry. Using a liquid-liquid extraction (20% methanol) at a pH ~ 7, as opposed to a solid-phase extraction used previously, substantially expedited the sample pretreatment process. The calibration curves showed a linear range from 0.5 to 100 ng/mL for aMT6s with a R2 of 0.9999 and from 1.5 to 100 ng/mL for 8‑OHdG with R2 of 0.9985. The recovery for 8‑OHdG and aMT6s was 102 ± 2% and 88 ± 4%, respectively. The limits of detection were 0.1 ng/mL for aMT6s and 0.5 ng/mL for 8‑OHdG, while the lower limits of quantification were 0.3 ng/mL for aMT6s and 1.0 ng/mL for 8‑OHdG. For both compounds, the retention time standard deviation was 0.03 min, and inter-day and intra-day variability, expressed as relative standard deviation (RSD), ranged from 4.5%–15.8%. The new method was successfully applied to analyze both compounds in the first morning and midday urine voids from five volunteers. The results support that this method is capable of rapidly and accurately measuring urinary 8‑OHdG and aMT6s simultaneously. This new method is expected to have important applications in biomedical and environmental health studies involving the oxidative stress pathophysiological pathway.