Shortcuts to Adiabatic Soliton Compression in Active Nonlinear Kerr Media

We implement variational shortcuts to adiabaticity for optical pulse compression in an active nonlinear Kerr medium with distributed amplification and spatially varying dispersion and nonlinearity. Starting with the hyperbolic secant ansatz, we employ a variational approximation to systematically derive dynamical equations, establishing analytical relationships linking the amplitude, width, and chirp of the pulse. Through the inverse engineering approach, we manipulate the distributed gain/loss, nonlinearity and dispersion profiles to efficiently compress the optical pulse over a reduced distance with high fidelity. In addition, we explore the dynamical stability of the system to illustrate the advantage of our protocol over conventional adiabatic approaches. Finally, we analyze the impact of tailored higher-order dispersion on soliton self-compression and derive physical constraints on the final soliton width for the complementary case of soliton expansion. The broader implications of our findings extend beyond optical systems, encompassing areas such as cold-atom and magnetic systems highlighting the versatility and relevance of our approach in various physical contexts.Comment: 9 pages, 6 figure

Systematic review of computational methods for drug combination prediction

Synergistic effects between drugs are rare and highly context-dependent and patient-specific. Hence, there is a need to develop novel approaches to stratify patients for optimal therapy regimens, especially in the context of personalized design of combinatorial treatments. Computational methods enable systematic in-silico screening of combination effects, and can thereby prioritize most potent combinations for further testing, among the massive number of potential combinations. To help researchers to choose a prediction method that best fits for various real-world applications, we carried out a systematic literature review of 117 computational methods developed to date for drug combination prediction, and classified the methods in terms of their combination prediction tasks and input data requirements. Most current methods focus on prediction or classification of combination synergy, and only a few methods consider the efficacy and potential toxicity of the combinations, which are the key determinants of therapeutic success of drug treatments. Furthermore, there is a need to further develop methods that enable dose-specific predictions of combination effects across multiple doses, which is important for clinical translation of the predictions, as well as model-based identification of biomarkers predictive of heterogeneous drug combination responses. Even if most of the computational methods reviewed focus on anticancer applications, many of the modelling approaches are also applicable to antiviral and other diseases or indications.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.Peer reviewe

Simultaneous Determination of Selegiline, Desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine on Dried Urine Spots by LC/MS/MS: Application to a Pharmacokinetic Study in Urine

Objective: Chiral analysis is a crucial method to differentiate selegiline intake from drug abuse. A dried urine spot (DUS) analytical method based on spotting urine samples (10 μL) onto dried spot collection cards, and followed by air-drying and extraction, was developed and validated for the determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine.Methods: Methanol (0.5 mL) was found to be the ideal extraction solvent for target extraction from DUSs under orbital-horizontal stirring on a lateral shaker at 1,450 rpm for 30 min. Determinations were performed by direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) under positive electrospray ionization conditions using multiple reaction monitoring mode. The chromatographic system consisted of a ChirobioticTM V2 column (2.1 × 250 mm, 5 μm) and a mobile phase of methanol containing 0.1% (v/v) glacial acetic acid and 0.02% (v/v) ammonium hydroxide.Results and conclusions: The calibration curves were linear from 50 to 5,000 ng/mL, with r > 0.995 for all analytes, imprecisions ≤ 15% and accuracies between −11.4 and 11.7%. Extraction recoveries ranged from 48.6 to 105.4% with coefficients of variation (CV) ≤ 13.7%, and matrix effects ranged from 45.4 to 104.1% with CV ≤ 10.3%. The lower limit of quantification was 50 ng/mL for each analyte. The present method is simple, rapid (accomplished in 12 min), sensitive, and validated by a pharmacokinetic study in human urine collected after a single oral administration of SG

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.This work was funded partly by the Ministry of Science and Technology 973 program (grant 2014CB542501 to H.Q.), the National Natural Science Foundation of China (grants 81425011 and 81330070 to H.Q. and grant 31200670 to L.W.), the Ministry of Science and Technology 863 program (grant 2012AA022403 to L.W.), a China Postdoctoral Science Foundation grant (2013M540970 to L.W.), and the Tsinghua-Peking Center for Life Sciences. H.Q. was supported partly by a Bayer Endowed Chair Professorship

It's How You Teach, Not What You Teach: Preschoolers Prefer Coordinative Instruction from Informants

When children make decisions about whom to trust or learn from, they consider not only the informant’s reliability but also the social bond. Previous research often assigned a social label to informants without investigating how the interactive dynamics between informants and children influence learning and trust. This study investigates 3- to 6-year-old children’s preference towards informants who deliver instructions with or without coordination. In two experiments, children evaluated coordinative and non-coordinative informants on game-playing capability, willingness to engage with or learn from the informants, and selective trust in unrelated tasks. Children consistently preferred coordinative informants, perceiving them as more capable and trustworthy, over informants who demonstrated the information without coordinative turn-taking. This preference persisted across age groups, challenging previous notions about children's preference for information completeness. The findings highlight the prosocial effects of coordination, extending its influence beyond peer relationships to significantly impact selective trust when learning from knowledgeable individuals

Modulation of cytokine/chemokine production in human macrophages by bisphenol A: A comparison to analogues and interactions with genistein

The immunotoxicant bisphenol A (BPA) may produce toxic effects on organs and systems, in part, by altering the secretion of cytokines and chemokines. However, systematic studies of the effects of BPA, let alone of its analogs and in cases when there are interactions with other chemicals, on innate immunity and cytokine modulation are limited. The objectives of this study were to investigate the immunomodulatory effects of: (1) BPA and its analogs, BPS and BPAF; and (2) the interaction between BPA and genistein (GEN), a partial estrogen agonist or antagonist. BPA, BPS, and BPAF were incubated with PMA-differentiated-U937 cells (a widely used cell line for primary human macrophages) at concentrations of 0, 0.1, 1, 10, 100 µM for up to 96 h. BPA (0, 0.1, 1, 10 µM) and GEN (0, 1, 10 µM) were also applied at various combinations. Cell viability and 30 cytokines/chemokines were measured. The results showed that the cell viability-inhibiting effect of these three bisphenols was BPAF > BPA > BPS. At 0.1 µM, BPA and BPAF generally increased the secretion of cytokines/chemokines, while BPS had minimal effects. All three bisphenols generally suppressed the secretion of cytokines/chemokines at 1 µM, while increased their secretion at 10 µM. The most increased cytokines/chemokines were interferon (IFN)-γ, interleukin (IL)-1RA, IL-8 and MIP-1β, and the most decreased was IL-10. GEN increased cell viability at low BPA concentrations but had no effect when BPA levels were high. In general, GEN attenuated the BPA-induced secretion of cytokines/chemokines but enhanced it at low BPA concentrations. In conclusion, this study showed that BPA, BPS, and BPAF were immunotoxic to macrophages: BPS was the least toxic, while BPAF was the most toxic. Further, GEN reversed suppressive effects on macrophages that resulted from exposure to high concentrations of BPA and produced synergetic effects with BPA at low concentrations