Targeted LC–MS derivatization for aldehydes and carboxylic acids with a new derivatization agent 4-APEBA

Based on the template of a recently introduced derivatization reagent for aldehydes, 4-(2-(trimethylammonio)ethoxy)benzeneaminium dibromide (4-APC), a new derivatization agent was designed with additional features for the analysis and screening of biomarkers of lipid peroxidation. The new derivatization reagent, 4-(2-((4-bromophenethyl)dimethylammonio)ethoxy)benzenaminium dibromide (4-APEBA) contains a bromophenethyl group to incorporate an isotopic signature to the derivatives and to add additional fragmentation identifiers, collectively enhancing the abilities for detection and screening of unknown aldehydes. Derivatization can be achieved under mild conditions (pH 5.7, 10 °C). By changing the secondary reagent (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide instead of sodium cyanoborohydride), 4-APEBA is also applicable to the selective derivatization of carboxylic acids. Synthesis of the new label, exploration of the derivatization conditions, characterization of the fragmentation of the aldehyde and carboxylic acid derivatives in MS/MS, and preliminary applications of the labeling strategy for the analysis of aldehydes in urine and plasma are described.     

Strategies to set global analytical quality specifications in laboratory medicine: 10 years on from the Stockholm consensus conference

The setting of analytical quality specifications in laboratory medicine has attracted attention for many years. Over time, many strategies were advocated and all had advantages and disadvantages. In the final decade of the last millennium, considerable confusion existed on how to define analytical quality specifications correctly and how to apply them in everyday practice. This led to wide professional interest. In 1999, a consensus conference sponsored by IUPAC, IFCC and WHO was held in Stockholm on “Strategies to Set Global Analytical Quality Specifications in Laboratory Medicine”. The consensus set useful and well-documented strategies for the setting of analytical quality specifications into a hierarchy with the best strategy at the highest level, namely, (1) Evaluation of the effect of analytical performance on clinical outcomes in specific clinical situations, (2) Evaluation of the effect of analytical performance on clinical decisions in general, (3) Published professional recommendations, (4) Performance goals set by regulatory bodies and EQAS organisers, and (5) Goals based on the current state of the art. Much success has been achieved since the promulgation of the statement with the approach being adopted by many in laboratory medicine for a very wide variety of purposes, particularly in quality management. However, there is a requirement for additional investigation of, inter alia, quality specifications for examinations done on measurements performed on ordinal and nominal scales, pre-analytical factors and matrix effects, examinations done as POCT, target values of control materials, and ways in which analytical quality specifications can be used both to set what is the optimum performance and as a tool for assessment of everyday practice.     

Towards Nanoscale Biomedical Devices in Medicine: Biofunctional and Spectroscopic Characterization of Superparamagnetic Nanoparticles

Medical interest in nanotechnology originates from a belief that nanoscale therapeutic devices can be constructed and directed towards its target inside the human body. Such nanodevices can be engineered by coupling superparamagnetic nanoparticle to biomedically active proteins. We hereby report the immobilization of a PhEst, a S-formylglutathione hydrolase from the psychrophilic P. haloplanktis TAC125 onto the gold coated surface of modified superparamagnetic core-shell nanoparticles (Fe₃O₄@Au). The synthesis of the nanoparticles is also reported. S-formylglutathione hydrolases constitute a family of ubiquitous enzymes which play a key role in formaldehyde detoxification both in prokaryotes and eukaryotes. PhEst was originally annotated as a putative feruloyl esterase, an enzyme that releases ferulic acid (an antioxidant reactive towards free radicals such as reactive oxygen species) from polysaccharides esters. Dynamic light scattering, scanning electron microscopy with energy dispersive X-ray spectroscopy, UV–visible absorption spectroscopy, fluorescence spectroscopy, magnetic separation technique and enzyme catalytic assay confirmed the chemical composition of the gold covered superparamagnetic nanoparticles, the binding and activity of the enzyme onto the nanoparticles. Activity data in U/ml confirmed that the immobilized enzyme is approximately 2 times more active than the free enzyme in solution. Such particles can be directed with external magnetic fields for bio-separation and focused towards a medical target for therapeutical as well as bio-sensor applications.     

A New Derivation of the Quantum Navier–Stokes Equations in the Wigner–Fokker–Planck Approach

A quantum Navier–Stokes system for the particle, momentum, and energy densities is formally derived from the Wigner–Fokker–Planck equation using a moment method. The viscosity term depends on the particle density with a shear viscosity coefficient which equals the quantum diffusion coefficient of the Fokker–Planck collision operator. The main idea of the derivation is the use of a so-called osmotic momentum operator, which is the sum of the phase-space momentum and the gradient operator. In this way, a Chapman–Enskog expansion of the Wigner function, which typically leads to viscous approximations, is avoided. Moreover, we show that the osmotic momentum emerges from local gauge theory.     

Homonuclear mixing sequences for perdeuterated proteins

We tested the performance of several (13)C homonuclear mixing sequences on perdeuterated microcrystalline ubiquitin. All sequences were applied without (1)H decoupling and at relatively low MAS frequencies. We found that RFDR gave the highest overall transfer efficiency and that DREAM performs surprisingly well under these conditions being twice as efficient in the aliphatic region of the spectrum than the other mixing sequences tested.     

Entanglement generated by dissipation and steady state entanglement of two macroscopic objects

Entanglement is a striking feature of quantum mechanics and an essential ingredient in most applications in quantum information. Typically, coupling of a system to an environment inhibits entanglement, particularly in macroscopic systems. Here we report on an experiment where dissipation continuously generates entanglement between two macroscopic objects. This is achieved by engineering the dissipation using laser and magnetic fields, and leads to robust event-ready entanglement maintained for 0.04 s at room temperature. Our system consists of two ensembles containing about 10(12) atoms and separated by 0.5 m coupled to the environment composed of the vacuum modes of the electromagnetic field. By combining the dissipative mechanism with a continuous measurement, steady state entanglement is continuously generated and observed for up to 1 h.     

220 μJ monolithic single-frequency Q-switched fiber laser at 2 μm by using highly Tm-doped germanate fibers

We report a unique all fiber-based single-frequency Q-switched laser in a monolithic master oscillator power amplifier configuration at ~1920 nm by using highly Tm-doped germanate fibers for the first time. The actively Q-switched fiber laser seed was achieved by using a piezo to press the fiber in the fiber Bragg grating cavity and modulate the fiber birefringence, enabling Q-switching with pulse width and repetition rate tunability. A single-mode polarization maintaining large core 25 μm highly Tm-doped germanate fiber was used in the power amplifier stage. For 80 ns pulses with 20 kHz repetition rate, we achieved 220 μJ pulse energy, which corresponds to a peak power of 2.75 kW with transform-limited linewidth.     

A Note on Aubin-Lions-Dubinskiĭ Lemmas

Strong compactness results for families of functions in seminormed nonnegative cones in the spirit of the Aubin-Lions-Dubinski? lemma are proven, refining some recent results in the literature. The first theorem sharpens slightly a result of Dubinski? (in Mat. Sb. 67(109):609–642, 1965) for seminormed cones. The second theorem applies to piecewise constant functions in time and sharpens slightly the results of Dreher and Jüngel (in Nonlinear Anal. 75:3072–3077, 2012) and Chen and Liu (in Appl. Math. Lett. 25:2252–2257, 2012). An application is given, which is useful in the study of porous-medium or fast-diffusion type equations.     

Entropy-stable and entropy-dissipative approximations of a fourth-order quantum diffusion equation

Structure-preserving numerical schemes for a nonlinear parabolic fourth-order equation, modeling the electron transport in quantum semiconductors, with periodic boundary conditions are analyzed. First, a two-step backward differentiation formula (BDF) semi-discretization in time is investigated. The scheme preserves the nonnegativity of the solution, is entropy stable and dissipates a modified entropy functional. The existence of a weak semi-discrete solution and, in a particular case, its temporal second-order convergence to the continuous solution is proved. The proofs employ an algebraic relation which implies the G-stability of the two-step BDF. Second, an implicit Euler and $q$ -step BDF discrete variational derivative method are considered. This scheme, which exploits the variational structure of the equation, dissipates the discrete Fisher information (or energy). Numerical experiments show that the discrete (relative) entropies and Fisher information decay even exponentially fast to zero.     

Product approximations for a class of quantum anharmonic oscillators

In this article, we investigate analytically and numerically a class of non-autonomous Schrödinger equations in one space dimension describing the dynamics of quantum anharmonic oscillators driven by time-dependent quartic interactions. We do so within a suitably constructed Faedo–Galerkin scheme by analyzing several product approximations for their solutions, which involve various exponential operator splittings. Our main objective is to study the convergence rates and the accuracy of such approximations, among which there are extensions of the Trotter–Kato product formula and several other variants. Crucial to our analysis is the knowledge of the lowest energy level and of the corresponding eigensolution to the associated time-independent problem, which we also compute within the very same framework.