Statistical detection of synergy: New methods and a comparative study.

Combination therapies are increasingly adopted as the standard of care for various diseases to improve treatment response, minimise the development of resistance and/or minimise adverse events. Therefore, synergistic combinations are screened early in the drug discovery process, in which their potential is evaluated by comparing the observed combination effect to that expected under a null model. Such methodology is implemented in the BIGL R-package which allows for a quick screening of drug combinations.

Hybrid x-ray laser-plasma/laser-synchrotron facility for pump-probe studies of the extreme state of matter at NRC "Kurchatov Institute".

We developed a hybrid optical pump-x-ray probe facility based on the "Kurchatov's synchrotron radiation source" and terawatt (TW) femtosecond laser. The bright x-ray photon source is based on either synchrotron radiation [up to 6 × 10 photons/(s mm mrad 0.1% bandwidth)] or laser-plasma generators (up to 10 photons/sr/pulse).

Malignant and benign thyroid nodule differentiation through the analysis of blood plasma with terahertz spectroscopy.

The liquid and lyophilized blood plasma of patients with benign or malignant thyroid nodules and healthy individuals were studied by terahertz (THz) time-domain spectroscopy and machine learning. The blood plasma samples from malignant nodule patients were shown to have higher absorption. The glucose concentration and miRNA-146b level were correlated with the sample's absorption at 1 THz.

Direct nose to brain delivery of small molecules: critical analysis of data from a standardized screening model in rats.

The blood-brain barrier (BBB) is often a limiting factor for getting drugs in the brain. Bypassing the BBB by intranasal (IN), or also called nose to brain (NTB), route is an interesting and frequently investigated concept for brain drug delivery. However, despite the body of evidence for IN drug delivery in literature over the last decades, reproducibility and interpretation of animal data remain challenging.

Free-beam spectral self-compression at supercritical peak powers.

We demonstrate free-beam spectral self-compression of ~100-GW femtosecond laser pulses due to self-phase modulation (SPM) in a transparent dielectric. While all the earlier studies of SPM-induced spectral narrowing have been performed using optical fibers, experiments and simulations presented in this Letter show that this type of spectral transformation can be implemented as a part of a full three-dimensional field-waveform dynamics and can be extended to peak powers ∼10 times higher than the critical power of self-focusing. With a properly chosen initial chirp, spectral self-compression is accompanied by pulse compression, providing spectral-temporal mode self-compression as a whole.

BIGL: Biochemically Intuitive Generalized Loewe null model for prediction of the expected combined effect compatible with partial agonism and antagonism.

Clinical efficacy regularly requires the combination of drugs. For an early estimation of the clinical value of (potentially many) combinations of pharmacologic compounds during discovery, the observed combination effect is typically compared to that expected under a null model. Mechanistic accuracy of that null model is not aspired to; to the contrary, combinations that deviate favorably from the model (and thereby disprove its accuracy) are prioritized.