Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media.

The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth.

Depth-resolved multimodal imaging: Wavelength modulated spatially offset Raman spectroscopy with optical coherence tomography.

A major challenge in biophotonics is multimodal imaging to obtain both morphological and molecular information at depth. We demonstrate a hybrid approach integrating optical coherence tomography (OCT) with wavelength modulated spatially offset Raman spectroscopy (WM-SORS). With depth colocalization obtained from the OCT, we can penetrate 1.

Quantifying Force and Viscoelasticity Inside Living Cells Using an Active-Passive Calibrated Optical Trap.

As described in the previous chapters, optical tweezers have become a tool of precision for in vitro single-molecule investigations, where the single molecule of interest most often is studied in purified form in an experimental assay with a well-controlled fluidic environment. A well-controlled fluidic environment implies that the physical properties of the liquid, most notably the viscosity, are known and the fluidic environment can, for calibrational purposes, be treated as a simple liquid.In vivo, however, optical tweezers have primarily been used as a tool of manipulation and not so often for precise quantitative force measurements, due to the unknown value of the spring constant of the optical trap formed within the cell's viscoelastic cytoplasm.

Quantitative determination of optical trapping strength and viscoelastic moduli inside living cells.

With the success of in vitro single-molecule force measurements obtained in recent years, the next step is to perform quantitative force measurements inside a living cell. Optical traps have proven excellent tools for manipulation, also in vivo, where they can be essentially non-invasive under correct wavelength and exposure conditions. It is a pre-requisite for in vivo quantitative force measurements that a precise and reliable force calibration of the tweezers is performed.

Adding functionalities to precomputed holograms with random mask multiplexing in holographic optical tweezers.

In this study, we present a method designed to generate dynamic holograms in holographic optical tweezers. The approach combines our random mask encoding method with iterative high-efficiency algorithms. This hybrid method can be used to dynamically modify precalculated holograms, giving them new functionalities-temporarily or permanently-with a low computational cost.

A preliminary study of the metabolic stability of a series of benzoxazinone derivatives as potent neuropeptide Y5 antagonists.

The metabolic stability of benzoxazinone derivatives, a potent series of NPY Y5 antagonists, has been investigated. This study resulted in the identification of the structural moieties prone to metabolic transformations and which strongly influenced the in vitro half-life. This provides opportunities to optimize the structure of this new class of NPY Y5 antagonists.

Synthesis of new benzoxazinone derivatives as neuropeptide Y5 antagonists for the treatment of obesity.

Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC(50) = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized and tested for NPY Y5 activity. Most of the compounds were found to be potent and selective NPY Y5 antagonists having nanomolar binding affinities for the NPY Y5 receptor and showing functional antagonism in the forskolin-induced cyclic AMP test.

Medicinal chemistry driven approaches toward novel and selective serotonin 5-HT6 receptor ligands.

Based on a medicinal chemistry guided hypothetical pharmacophore model, novel series of indolyl sulfonamides have been designed and prepared as selective and high-affinity serotonin 5-HT(6) receptor ligands. Furthermore, based on a screening approach of a discovery library, a series of benzoxazinepiperidinyl sulfonamides were identified as selective 5-HT(6) ligands. Many of the compounds described in this paper possess excellent affinities, displaying pK(i) values greater than 8 (some even >9) and high selectivities against a wide range (>50) of other CNS relevant receptors.