Extending time-domain ptychography to generalized phase-only transfer functions

We extend the time-domain ptychographic iterative engine to generalized spectral phase-only transfer functions. The modified algorithm, i$^2$PIE, is described and its robustness is demonstrated by different numeric simulations. The concept is experimentally verified by reconstruction of a complex supercontinuum pulse from an all normal dispersion fiber.Comment: 5 pages, 4 figures, submitted to Optic

Time-domain ptychography

Through dedicated measurements in the optical regime we demonstrate that ptychography can be applied to reconstruct complex-valued object functions that vary with time from a sequence of spectral measurements. A probe pulse of approximately 1 ps duration, time delayed in increments of 0.25 ps is shown to recover dynamics on a ten times faster time scale with an experimental limit of approximately 5 fs.Comment: 5 pages, 4 figures, new title and minor text change

Low noise all-fiber amplification of a coherent supercontinuum at 2 \mu m and its limits imposed by polarization noise

We report the amplification of an all-normal dispersion supercontinuum pulse in a Thulium / Holmium co-doped all-fiber chirped pulse amplification system. With a -20 dB bandwidth of more than 300 nm in the range 1800-2100 nm the system delivers high quality 66 fs pulses with more than 70 kW peak power directly from the output fiber. The coherent seeding of the entire emission bandwidth of the doped fiber and the stability of the supercontinuum generation dynamics in the silicate glass all-normal dispersion photonic crystal fiber result in excellent noise characteristics of the amplified ultrashort pulses

Enzyme‐assisted HPTLC method for the simultaneous analysis of inositol phosphates and phosphate

Background The analysis of myo‐inositol phosphates (InsPx) released by phytases during phytic acid degradation is challenging and time‐consuming, particularly in terms of sample preparation, isomer separation, and detection. However, a fast and robust analysis method is crucial when screening for phytases during protein engineering approaches, which result in a large number of samples, to ensure reliable identification of promising novel enzymes or target variants with improved characteristics, for example, pH range, thermal stability, and phosphate release kinetics. Results The simultaneous analysis of several InsPx (InsP1‐InsP4 and InsP5 + 6) as well as free phosphate was established on cellulose HPTLC plates using a buffered mobile phase. Inositol phosphates were subsequently stained using a novel enzyme‐assisted staining procedure. Immobilized InsPx were hydrolyzed by a phytase solution of Quantum® Blueliquid 5G followed by a molybdate reagent derivatization. Resulting blue zones were captured by DAD scan. The method shows good repeatability (intra‐day and intra‐lab) with maximum deviations of the Rf value of 0.01. The HPTLC method was applied to three commercially available phytases at two pH levels relevant to the gastrointestinal tract of poultry (pH 5.5 and pH 3.6) to observe their phytate degradation pattern and thus visualize their InsPx fingerprint. Conclusion This HPTLC method presents a semi‐high‐throughput analysis for the simultaneous analysis of phytic acid and the resulting lower inositol phosphates after its enzymatic hydrolysis and is also an effective tool to visualize the InsPx fingerprints and possible accumulations of inositol phosphates

Enzyme‐assisted HPTLC method for the simultaneous analysis of inositol phosphates and phosphate

Background The analysis of myo-inositol phosphates (InsPx) released by phytases during phytic acid degradation is challenging and time-consuming, particularly in terms of sample preparation, isomer separation, and detection. However, a fast and robust analysis method is crucial when screening for phytases during protein engineering approaches, which result in a large number of samples, to ensure reliable identification of promising novel enzymes or target variants with improved characteristics, for example, pH range, thermal stability, and phosphate release kinetics. Results The simultaneous analysis of several InsPx (InsP1-InsP4 and InsP5 + 6) as well as free phosphate was established on cellulose HPTLC plates using a buffered mobile phase. Inositol phosphates were subsequently stained using a novel enzyme-assisted staining procedure. Immobilized InsPx were hydrolyzed by a phytase solution of Quantum® Blueliquid 5G followed by a molybdate reagent derivatization. Resulting blue zones were captured by DAD scan. The method shows good repeatability (intra-day and intra-lab) with maximum deviations of the Rf value of 0.01. The HPTLC method was applied to three commercially available phytases at two pH levels relevant to the gastrointestinal tract of poultry (pH 5.5 and pH 3.6) to observe their phytate degradation pattern and thus visualize their InsPx fingerprint. Conclusion This HPTLC method presents a semi-high-throughput analysis for the simultaneous analysis of phytic acid and the resulting lower inositol phosphates after its enzymatic hydrolysis and is also an effective tool to visualize the InsPx fingerprints and possible accumulations of inositol phosphates

Evaluation of the pharmacokinetic-pharmacodynamic relationship of praziquantel in the Schistosoma mansoni mouse model

After more than 40 years of use, Praziquantel (PZQ) still remains the drug of choice for the treatment of intestinal and urogenital schistosomiasis. Its anti-parasitic activity resides primarily in the (R)-enantiomer. Hitherto neither the molecular target nor the pharmacokinetic-pharmacodynamic relationship have been fully elucidated. Here we investigated the efficacy and pharmacokinetics of PZQ in the Schistosoma mansoni mouse model to determine the key factors that drive its efficacy. Dose-response studies with racemic PZQ with or without addition of an irreversible pan-cytochrome P450 (CYP) inhibitor, 1-aminobenzotriazole (ABT), were performed. In addition, efficacy of PZQ in the presence of the CYP inducer, dexamethasone (DEX), was determined. Plasma samples were obtained by tail vein bleeding at 4 time points. The (R)-PZQ levels were determined using a LC-MS/MS method. Non-compartmental pharmacokinetic analysis was performed using PKsolver. In addition, experiments using an enhanced in vitro assay were conducted. We found that the use of ABT increased (R)-PZQ plasma exposures in the systemic circulation by ~10 to 20 fold but the latter were not predictive of efficacy. The use of DEX decreased plasma exposures of (R)-PZQ in the systemic circulation by ~10 fold without reducing efficacy. We extrapolated the (R)-PZQ concentrations in mouse portal vein / mesenteric veins from the systemic exposures and found that a free exposure of (R)-PZQ of ~ 20 μM*h in the portal vein was needed to obtain a worm burden reduction >60%. It is suggested that the high (R)-PZQ concentrations available before the hepatic first pass metabolism drive the efficacy against S. mansoni adult worms residing in the mesenteric veins. It is then possible that the current dosing regimen of 40 mg/kg in preventive chemotherapy programs may provide suboptimal concentrations in low-weight patients such as children, due to smaller total amounts of drug administered, and may consequently result in lower cure rates

Novel time domain ptychography, i2PIE, for improved contrast in nonlinear microscopy

We present a novel nonlinear microscopy modality using a time-domain ptychographic phase measurement, i2PIE, to compress 80 MHz supercontinuum pulses from an ANDi PCF used as excitation source, improving contrast at reduced average power

Generalized spectral phase-only time-domain ptychographic phase reconstruction applied in nonlinear microscopy

Nonlinear microscopy has evolved over the last few decades to become a powerful tool for imaging and spectroscopic applications in biological sciences. In this study, I$^2$PIE, a novel spectral phase control technique, was implemented in order to compress broad-bandwidth supercontinuum light pulses generated in an all-normal-dispersion (ANDi) photonic crystal fiber (PCF). The technique, based on time-domain ptychography, is demonstrated here in a nonlinear microscopy application for the first time, to the best of our knowledge. The first real-world application of this technique for second-harmonic generation and two-photon excitation fluorescence microscopies in biological samples is presented. We further show that in our implementation, I$^2$PIE leads to improved contrast and signal-to-noise ratios in the generated images, compared to conventional compression techniques used in nonlinear microscopy.Comment: Copyright 2020 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibite

Do Feelings of Defeat and Entrapment Change over Time? An Investigation of the Integrated Motivational—Volitional Model of Suicidal Behaviour Using Ecological Momentary Assessments

(1) Background. Defeat and entrapment have been highlighted as major risk factors of suicidal ideation and behavior. Nevertheless, little is known about their short-term variability and their longitudinal association in real-time. Therefore, this study aims to investigate whether defeat and entrapment change over time and whether defeat predicts entrapment as stated by the integrated motivational–volitional model of suicidal behavior. (2) Methods. Healthy participants (n = 61) underwent a 7-day smartphone-based ecological momentary assessment (EMA) on suicidal ideation/behavior and relevant risk factors, including defeat and entrapment and a comprehensive baseline (T0) and post (T2) assessment. (3) Results. Mean squared successive differences (MSSD) and intraclass correlations (ICC) support the temporal instability as well as within-person variability of defeat and entrapment. Multilevel analyses revealed that during EMA, defeat was positively associated with entrapment at the same measurement. However, defeat could not predict entrapment to the next measurement (approximately two hours later). (4) Conclusion. This study provides evidence on the short-term variability of defeat and entrapment highlighting that repeated measurement of defeat and entrapment—preferably in real time—is necessary in order to adequately capture the actual empirical relations of these variables and not to overlook significant within-person variability. Further research—especially within clinical samples—seems warranted

Torn between living or dying—analyses of influencing factors on suicide ambivalence and its longitudinally impact on suicidal ideation and behavior in a high-risk sample

IntroductionFindings on the role of suicide ambivalence, an individual's wish to live (WL), and wish to die (WD) in the development of suicidality have been heterogenous. The main goal of this study was to examine associations of these constructs within the past week with sociodemographic factors and to longitudinally investigate their predictive power for suicidal ideation (SI) and suicide attempts (SA).MethodsN = 308 patients (54% female; M = 36.92 years, SD = 14.30), admitted to a psychiatric ward due to suicidality, were assessed for all constructs after admission, after six, nine, and 12 months. Data were analyzed with univariate fixed-effect models and lagged mixed-effect regression models.ResultsDecreased, WL increased post-baseline. Gender showed no significant link to ambivalence, WD, and WL. Ambivalence and WD correlated negatively with age and positively with depressiveness. More participants in a relationship showed a WL compared with single/divorced/widowed participants. More single participants or those in a relationship showed ambivalence than divorced/widowed participants. More single participants showed a WD than participants in a relationship/divorced/widowed. Longitudinally, ambivalence and WD predicted SI and SA.ConclusionThe findings underscore the importance of taking suicide ambivalence and WD into account in risk assessment and treatment