Quantitative determination of pravastatin and its metabolite 3α‐hydroxy pravastatin in plasma and urine of pregnant patients by LC‐MS/MS

This report describes the development and validation of a chromatography/tandem mass spectrometry method for the quantitative determination of pravastatin and its metabolite (3α‐hydroxy pravastatin) in plasma and urine of pregnant patients under treatment with pravastatin, as part of a clinical trial. The method includes a one‐step sample preparation by liquid–liquid extraction. The extraction recovery of the analytes ranged between 93.8 and 99.5% in plasma. The lower limits of quantitation of the analytes in plasma samples were 0.106 ng/mL for pravastatin and 0.105 ng/mL for 3α‐hydroxy pravastatin, while in urine samples they were 19.7 ng/mL for pravastatin and 2.00 ng/mL for 3α‐hydroxy pravastatin. The relative deviation of this method was <10% for intra‐ and interday assays in plasma and urine samples, and the accuracy ranged between 97.2 and 106% in plasma, and between 98.2 and 105% in urine. The method described in this report was successfully utilized for determining the pharmacokinetics of pravastatin in pregnant patients enrolled in a pilot clinical trial for prevention of preeclampsia. Copyright © 2015 John Wiley & Sons, Ltd.     

Spin fluctuations in hydrogen-stabilized Laves phase UTi2H5

Uranium Laves phase UTi₂ does not exist in a pure form, but can be stabilised by the presence of hydrogen, which can be absorbed in concentration exceeding 5?H atoms/f.u. Low temperature specific heat, magnetic susceptibility, and resistivity indicate that UTi₂H₅ is a spin fluctuator close to the verge of magnetic ordering. Its susceptibility follows at high temperatures the Curie–Weiss law with U effective moment µ_eff[ ?= 3.1?µ_B/U and paramagnetic Curie temperature Θ_p = ?200 K. The temperature dependence of specific heat exhibits a pronounced and weakly field dependent upturn in C_p/T versus T below 10 K reflecting the effect of spin fluctuations. It can be described by an additional T^½ term. The Sommerfeld coefficient γ = 256?mJ/mol K² classifies the compound as a mid-weight heavy fermion. Spin fluctuations are affecting also electrical and thermal transport and thermoelectric power, which all resemble UAl₂. A lattice anomaly at ≈ 240?K, attributed to the melting of hydrogen sublattice, reflects in most of bulk properties.     

Fused Bis(hemi-indigo): Broad-Range Wavelength-Independent Photoswitches

Wavelength-independent conversion of organic photoswitches in the photostationary state is a rare phenomenon that opens up a way for many practical applications. In this work, three fused bis(hemi-indigo) derivatives with different substitution patterns were synthesized and their photoswitching was investigated by optical spectroscopy, real-time NMR spectroscopy and TD-DFT calculations. We disclosed that the Z-E photoisomerization of the meta-bis(hemi-indigo) derivative was remarkably independent of the irradiation wavelength from UV up to yellow light. The wavelength-independent forward photoswitching together with the inhibited backward photoisomerization, high thermal stability of the photoinduced isomers as well as significant overlap between the photoswitch absorption and the solar spectrum allows to suggest bis(hemi-indigo) derivatives as promising candidates for molecular solar thermal energy storage (MOST) systems.     

The diversity challenge in directed protein evolution

Over the past decade, we have witnessed a bloom in the field of evolutive protein engineering which is fueled by advances in molecular biology techniques and high-throughput screening technology. Directed protein evolution is a powerful algorithm using iterative cycles of random mutagenesis and screening for tailoring protein properties to our needs in industrial applications and for elucidating proteins' structure function relationships. This review summarizes, categorizes and discusses advantages and disadvantages of random mutagenesis methods used for generating genetic diversity. These random mutagenesis methods have been classified into four main categories depending on the method employed for nucleotide substitutions: enzyme based methods (Category I), synthetic chemistry based methods (Category II), whole cell methods (Category III) and combined methods (Category I-II, I-III and II-III). The basic principle of each method is discussed and varied mutagenic conditions are summarized in Tables and compared (benchmarked) to each other in terms of: mutational bias, controllable mutation frequency, ability to generate consecutive nucleotide substitutions and subset diversity, dependency on gene length, technical simplicity/robustness and cost-effectiveness. The latter comparison shows how highly-biased and limited current diversity creating methods are. Based on these limitations, strategies for generating diverse mutant libraries are proposed and discussed (RaMuS-Flowchart; KISS principle). We hope that this review provides, especially for researchers just entering the field of directed evolution, a guide for developing successful directed evolution strategies by selecting complementary methods for generating diverse mutant libraries.     

Recent advances in laser self-injection locking to high-Q microresonators

The stabilization and manipulation of laser frequency by means of an external cavity are nearly ubiquitously used in fundamental research and laser applications. While most of the laser light transmits through the cavity, in the presence of some back-scattered light from the cavity to the laser, the self-injection locking effect can take place, which locks the laser emission frequency to the cavity mode of similar frequency. The self-injection locking leads to dramatic reduction of laser linewidth and noise. Using this approach, a common semiconductor laser locked to an ultrahigh-Q microresonator can obtain sub-Hertz linewidth, on par with state-of-the-art fiber lasers. Therefore it paves the way to manufacture high-performance semiconductor lasers with reduced footprint and cost. Moreover, with high laser power, the optical nonlinearity of the microresonator drastically changes the laser dynamics, offering routes for simultaneous pulse and frequency comb generation in the same microresonator. Particularly, integrated photonics technology, enabling components fabricated via semiconductor CMOS process, has brought increasing and extending interest to laser manufacturing using this method. In this article, we present a comprehensive tutorial on analytical and numerical methods of laser self-injection locking, as well a review of most recent theoretical and experimental achievements.     

The Role of Metal Ions in the Study of Ancient Paper by Electron Paramagnetic Resonance

Samples from covers and endleaves of sixteenth to eighteenth century books in good conservation state from the Biblioteca Nazionale Marciana in Venice have been investigated by means of electron paramagnetic resonance (EPR) spectroscopy and optical microscopy to characterize the embedded paramagnetic species and to test differences and similarities of the materials in the two types of book components. We detected the Mn(II), Fe(III), and Cu(II) paramagnetic ions, and analyzed their EPR signals by comparing them with previous results in literature of EPR studies on paper. Interestingly, the Mn(II) EPR spectrum profile appears as a fingerprint for samples coming from the same book, either from cover or endleaf, and it looks different for samples extracted from different books. We discuss the role of EPR as a spectroscopic tool for characterizing the interaction of the ions with the paper components and as possible agents of degradation.     

Application of new synthesized zwitterionic surfactants as hair shampoo components

Abstract

The purpose of the study was to applicate new synthesized zwitterionic surfactants as hair shampoo components. Hair shampoos formulated for the study contained newly synthesized sulfobetaines at a concentration of 2%. The above additives were evaluated to determine their effect on shampoo dynamic viscosity, texture, yield stress, foaming properties and surface tension of aqueous shampoo solutions. The viscosity of the sulfobetaine-enriched hair shampoos ranged between 6,000 and 21,000?mPa·s, which ensures the required application properties of the formulated products. The yield stress in three prototypical shampoos was equal to approximately 10?Pa, which represents the minimum value that should characterize cosmetics of this type. The sulfobetaines added to the formulations were not found to significantly affect the parameters of hardness and adhesive force. All the formulations under study, except for the shampoo containing N-dodecyl-N-piperidinium-1-propanesulfonate, exhibited good foaming properties. The incorporation of sulfobetaines into hair shampoos contributes to an effective decrease in the surface tension of their aqueous solutions, which may indicate beneficial washing properties. The use of the proposed sulfobetaines in hair shampoos favorably modifies their physicochemical and functional properties. The findings of the study can provide useful insights for the formulation of hair shampoos containing zwitterionic surfactants.