"Molecular chameleons". Design and synthesis of C-4-substituted imidazole fleximers

The synthesis of two flexible nucleosides is presented. The "fleximers" feature the purine ring system split into its imidazole and pyrimidine components. This modification serves to introduce flexibility to the nucleoside while still retaining the elements essential for molecular recognition. As a result, these structurally innovative nucleosides can more readily adapt to capricious binding sites and, as such, should find use for investigating enzyme-coenzyme as well as nucleic acid-protein interactions.     

Regulation of prokineticin 2 expression by light and the circadian clock

Background  

The suprachiasmatic nucleus (SCN) contains the master circadian clock that regulates daily rhythms of many physiological and behavioural processes in mammals. Previously we have shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCN output molecule responsible for circadian locomotor rhythms. As light is the principal zeitgeber that entrains the circadian oscillator, and PK2 expression is responsive to nocturnal light pulses, we further investigated the effects of light on the molecular rhythm of PK2 in the SCN. In particular, we examined how PK2 responds to shifts of light/dark cycles and changes in photoperiod. We also investigated which photoreceptors are responsible for the light-induced PK2 expression in the SCN. To determine whether light requires an intact functional circadian pacemaker to regulate PK2, we examined PK2 expression in cryptochrome1,2-deficient (Cry1-/-Cry2-/-) mice that lack functional circadian clock under normal light/dark cycles and constant darkness.     

Optimization of a long-period grating-based Mach-Zehnder interferometer for temperature measurement

An approach to optimize the design of the long-period grating pair as a temperature sensor device is presented, implemented by using a long-period grating (LPG) pair with a small separation (of around 2 mm) and scaling down their physical length by a factor greater than 2. The technique allows the interferometer formed not only to measure temperature variations over distances as small as the overall length of the grating pair (18 mm) but also to reduce the cladding losses between the LPGs forming the pair. This approach enhances the sharpness of the interference fringes (IFs) and the pits (Pts) in the transmission spectrum and, as a result, a high resolution sensor is obtained. The LPG pair is fabricated in the appropriate photosensitive single mode/core fibres, without being restricted to the use of dual core or other special fibres, thus exploiting the sensitivities of various fibres and reducing the overall system cost. In this work, the effectiveness of this technique is demonstrated by fabricating a small-scale LPG pair in a boron-germanium co-doped single mode fibre, with particular attention being paid to the higher order cladding modes. The sensitivity of the device thus created is 0.31 nm/°C with a root-mean-square (rms) deviation of 0.28 nm in the wavelength measurement, which corresponds to a temperature variation of approximately 0.9 °C. This was achieved while using a relatively low-resolution (0.6 nm) Optical Spectrum Analyzer to detect the wavelength changes of the device and was further improved to 0.7 °C when using an OSA with a resolution of 0.1 nm.     

Cucurbit[7]uril Inclusion Complexes with Benzimidazole Derivatives: A Computational Study

Molecular dynamics (MD) simulations were carried out to study the host–guest complexation in aqueous solution between cucurbit[7]uril (CB7) and the neutral and protonated forms of benzimidazole derivatives. Complexation occurs via encapsulation of the hydrophobic part (benzene ring) of the guest within the CB7 hydrophobic cavity, and the interactions of the amine group(s) of the imidazole ring of the guest with the CB7 carbonyl portals. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method is used to estimate the host–guest Gibbs energy of binding. The results indicate that CB7 binds the protonated form more strongly than the neutral one, and that the dominant contribution to the Gibbs energy of complexation for the neutral and protonated guests is associated, respectively, with the host–guest van der Waals and electrostatic interactions. Quantum chemical calculations using dispersion-corrected density functional theory (DFT) are used to calculate the binding affinities and to predict the pK_a values of the free and complexed guests. The calculated pK_a values for the free guests reveal excellent agreement with the experimental values, while for the complexed guests, general trends are obtained.     

Multivariate numerical differentiation

We present an innovative method for multivariate numerical differentiation i.e. the estimation of partial derivatives of multidimensional noisy signals. Starting from a local model of the signal consisting of a truncated Taylor expansion, we express, through adequate differential algebraic manipulations, the desired partial derivative as a function of iterated integrals of the noisy signal. Iterated integrals provide noise filtering. The presented method leads to a family of estimators for each partial derivative of any order. We present a detailed study of some structural properties given in terms of recurrence relations between elements of a same family. These properties are next used to study the performance of the estimators. We show that some differential algebraic manipulations corresponding to a particular family of estimators lead implicitly to an orthogonal projection of the desired derivative in a Jacobi polynomial basis functions, yielding an interpretation in terms of the popular least squares. This interpretation allows one to (1) explain the presence of a spatial delay inherent to the estimators and (2) derive an explicit formula for the delay. We also show how one can devise, by a proper combination of different elementary estimators of a given order derivative, an estimator giving a delay of any prescribed value. The simulation results show that delay-free estimators are sensitive to noise. Robustness with respect to noise can be highly increased by utilizing voluntary-delayed estimators. A numerical implementation scheme is given in the form of finite impulse response digital filters. The effectiveness of our derivative estimators is attested by several numerical simulations.