A tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluation

The crystallographically determined structure of biologically active 4,4-dichloro-1,3-diphenyl-4-telluraoct-2-en-1-one, 3, shows the coordination geometry for Te to be distorted psi-pentagonal bipyramidal based on a C2OCl3(lone pair) donor set. Notable is the presence of an intramolecular axial Te center dot center dot center dot O (carbonyl) interaction, a design element included to reduce hydrolysis. Raman and molecular modelling studies indicate the persistence of the Te center dot center dot center dot O(carbonyl) interaction in the solution (CHCl3) and gasphases, respectively. Docking studies of 3' (i.e. original 3 less one chloride) with Cathepsin B reveals a change in the configuration about the vinyl C = C bond. i.e. to E from Z (crystal structure). This isomerism allows the optimisation of interactions in the complex which features a covalent Te-SGCys29 bond. Crucially, the E configuration observed for 3' allows for the formation of a hypervalent Te center dot center dot center dot O interaction as well as an O center dot center dot center dot H-O hydrogen bond with the Gly27 and Glu122 residues, respectively. Additional stabilisation is afforded by a combination of interactions spanning the S1, S2, S1' and S2' sub-sites of Cathepsin B. The greater experimental inhibitory activity of 3 compared with analogues is rationalised by the additional interactions formed between 3' and the His110 and His111 residues in the occluding loop, which serve to hinder the entrance to the active site. (C) 2012 Elsevier B.V. All rights reserved.

Nanofiber-based spectroscopy of organic molecules

This thesis reports on the experimental realization of nanofiber-based spectroscopy of organic molecules. The light guided by subwavelength diameter optical nanfibers exhibits a pronounced evanescent field surrounding the fiber which yields high excitation and emission collection efficiencies for molecules on or near the fiber surface.rnThe optical nanofibers used for the experiments presented in this thesis are realized as thernsub-wavelength diameter waist of a tapered optical fiber (TOF). The efficient transfer of thernlight from the nanofiber waist to the unprocessed part of the TOF depends critically on therngeometric shape of the TOF transitions which represent a nonuniformity of the TOF. Thisrnnonuniformity can cause losses due to coupling of the fundamental guided mode to otherrnmodes which are not guided by the taper over its whole length. In order to quantify the lossrnfrom the fundamental mode due to tapering, I have solved the coupled local mode equationsrnin the approximation of weak guidance for the three layer system consisting of fiber core andrncladding as well as the surrounding vacuum or air, assuming the taper shape of the TOFsrnused for the experiments presented in this thesis. Moreover, I have empirically studied therninfluence of the TOF geometry on its transmission spectra and, based on the results, I haverndesigned a nanofiber-waist TOF with broadband transmission for experiments with organicrnmolecules.rnAs an experimental demonstration of the high sensitivity of nanofiber-based surface spectroscopy, I have performed various absorption and fluorescence spectroscopy measurements on the model system 3,4,9,10-perylene-tetracarboxylic dianhydride (PTCDA). The measured homogeneous and inhomogeneous broadening of the spectra due to the interaction of the dielectric surface of the nanofiber with the surface-adsorbed molecules agrees well with the values theoretically expected and typical for molecules on surfaces. Furthermore, the self-absorption effects due to reasorption of the emitted fluorescence light by circumjacent surface-adsorbed molecules distributed along the fiber waist have been analyzed and quantified. With time-resolved measurements, the reorganization of PTCDA molecules to crystalline films and excimers can be observed and shown to be strongly catalyzed by the presence of water on the nanofiber surface. Moreover, the formation of charge-transfer complexes due to the interaction with localized surface defects has been studied. The collection efficiency of the molecular emission by the guided fiber mode has been determined by interlaced measurements of absorption and fluorescence spectra to be about 10% in one direction of the fiber.rnThe high emission collection efficiency makes optical nanofibers a well-suited tool for experiments with dye molecules embedded in small organic crystals. As a first experimental realization of this approach, terrylene-doped para-terphenyl crystals attached to the nanofiber-waist of a TOF have been studied at cryogenic temperatures via fluorescence and fluorescence excitation spectroscopy. The statistical fine structure of the fluorescence excitation spectrum for a specific sample has been observed and used to give an estimate of down to 9 molecules with center frequencies within one homogeneous width of the laser wavelength on average for large detunings from resonance. The homogeneous linewidth of the transition could be estimated to be about 190MHz at 4.5K.

Distortion-free enhancement of terahertz signals measured by electro-optic sampling. I. Theory

We present three methods for the distortion-free enhancement of THz signals measured by electro-optic sampling in zinc blende-type detector crystals, e.g., ZnTe or GaP. A technique commonly used in optically heterodyne-detected optical Kerr effect spectroscopy is introduced, which is based on two measurements at opposite optical biases near the zero transmission point in a crossed polarizer detection geometry. In contrast to other techniques for an undistorted THz signal enhancement, it also works in a balanced detection scheme and does not require an elaborate procedure for the reconstruction of the true signal as the two measured waveforms are simply subtracted to remove distortions. We study three different approaches for setting an optical bias using the Jones matrix formalism and discuss them also in the framework of optical heterodyne detection. We show that there is an optimal bias point in realistic situations where a small fraction of the probe light is scattered by optical components. The experimental demonstration will be given in the second part of this two-paper series [J. Opt. Soc. Am. B, doc. ID 204877 (2014, posted online)].

A single response mechanism is responsible for evolutionary adaptive variation in a bird’s laying date

Many proximate factors determine a bird’s laying date, including environmental and social stimuli as well as individual responses to internal and external factors. However, the relative importance of these factors has not been experimentally demonstrated. Here we show that (i) large differences in the onset of first clutches between different populations result from variation in different responses to photoperiod and not from variation in responses to any other proximate factors and (ii) the same response mechanism causes maladaptive laying dates in habitats modified by humans. We present, to our knowledge, the first experimental demonstration that a single response mechanism is responsible for evolutionary adaptive intraspecific variation in a vertebrate life history trait.

165 km ultra-long Raman fibre laser in the C-band

We present the first experimental demonstration of a Raman fibre laser operation with a resolvable ~0.6 kHz mode spacing operating at 1551nm. Our laser has a record cavity length of 165 km.

Soliton dynamics in transmission through ultralong lasers

We have studied the dynamics and stability of solitonic pulses (including soliton interaction) across URFL transmission links, as well as the dependence of these dynamics on cavity design (length, symmetry, reflectivity) and input pulse characteristics. The first experimental demonstration of long-distance ldquotruerdquo soliton propagation through optical fibre. The results conclude that even relatively long links of the order of 50 km show excellent nonlinear resilience and are capable of providing virtually transparent transmission under a broad range of input pulse characteristics.

True soliton transmission through ultra-long laser links

We present the first experimental demonstration of true (not loss managed) soliton pulse transmission in conventional optical fibre. Experimental FROG spectrograms and numerical simulations confirm the soliton pulse evolution dynamics.

Dual-wavelength, ultralong Raman laser with Rayleigh-scattering feedback

We present experimental demonstration of a 200-km-long, dual-wavelength Raman laser utilizing two slightly different-wavelength fiber Bragg gratings, one on each side of the fiber span. The obtained results clearly prove the generation of two independent Raman lasers with a distributed “random” Rayleigh scattering mirror forming a cavity together with each of the individual fiber Bragg grating reflectors.

Fibre Bragg grating sensor interrogation using an acousto-optic tunable filter and low-coherence interferometry

We describe how an acousto-optic tunable filter can be used to both demultiplex the signals from multiple fibre Bragg grating sensors and simultaneously provide wide bandwidth signal demodulation in a system using interferometric wavelength shift detection. In an experimental demonstration, the approach provided a noise limited strain resolution of 24.9 n epsilon Hz(-1/ 2) at 15 Hz.

Channelled spectrum liquid refractometer

We describe an experimental demonstration of a novel technique for liquid refractometry. A channeled spectrum is produced from an optical beam generated by a diode laser operating below threshold by intercepting half of the beam with a liquid cell. The spectrum is analyzed using a grating and a linear CCD array and provides information on the refractive index of the liquid. The experimental results show that accuracies of better than 0.3% in the index may be obtained with the present method.

Long-distance soliton transmission through ultralong fiber lasers

We present the first experimental demonstration (to our knowledge) of long-distance unperturbed fundamental optical soliton transmission in conventional single-mode optical fiber. The virtual transparency in the fiber required for soliton transmission, over 15 complete periods, was achieved by using an ultralong Raman fiber laser amplification scheme. Optical soliton pulse duration, pulse bandwidth, and peak intensity are shown to remain constant along the transmission length. Frequency-resolved optical gating spectrograms and numerical simulations confirm the observed optical soliton dynamics.

40 Gbit/s asynchronous digital optical regenerator

We present the first experimental demonstration of an asynchronous digital optical regenerator at 42.67 Gbit/s. The system effectively retimes incoming asynchronous data bursts to a local clock without burst mode clock recovery and converts the signal to a desired wavelength and duty cycle.

Coupling between counterpropagating cladding modes in fiber Bragg gratings

We present an experimental demonstration of energy transfer between counterpropagating cladding modes in a fiber Bragg grating (FBG). A strong FBG written in a standard photosensitive optical fiber is illuminated with a single cladding mode, and the power transferred between the forward propagating cladding mode and different backward propagating cladding modes is measured by using two auxiliary long period gratings. Resonances between cladding modes having 30 pm bandwidth and 8 dB rejection have been observed.

Humidity insensitive TOPAS polymer fiber Bragg grating sensor

We report the first experimental demonstration of a humidity insensitive polymer optical fiber Bragg grating (FBG), as well as the first FBG recorded in a TOPAS polymer optical fiber in the important low loss 850nm spectral region. For the demonstration we have fabricated FBGs with resonance wavelength around 850 nm and 1550 nm in single-mode microstructured polymer optical fibers made of TOPAS and the conventional poly (methyl methacrylate) (PMMA). Characterization of the FBGs shows that the TOPAS FBG is more than 50 times less sensitive to humidity than the conventional PMMA FBG in both wavelength regimes. This makes the TOPAS FBG very appealing for sensing applications as it appears to solve the humidity sensitivity problem suffered by the PMMA FBG. © 2011 Optical Society of America.

Basic elements for microfiber photonics : micro/nanofibers and microfiber coil resonators

The basic functional element of microfiber photonics is a microfiber coil resonator (MCR), which potentially can perform filtering, time delay, and nonlinear transformations of electromagnetic waves, as well as sensing of the ambient medium. The first experimental demonstration of an MCR has been recently performed by researchers of the OFS Laboratories (Optical Fiber Communication Conference 2007, Postdeadline paper PDP46). This paper follows up on the later publication presenting a brief introduction to the theory, transmission properties and applications of optical micro/nanofibers and MCRs. Fabrication of MCRs in air and in liquid is reported. For the MCR immersed in liquid, the Q-factor exceeding 60 000 is achieved. © 2008 IEEE.