LC Method for the Determination of Meropenem in Cerebrospinal Fluid: Application to Therapeutic Drug Monitoring

A simple, rapid and accurate liquid chromatography method using ultrafiltration to pretreat cerebrospinal fluid (CSF) samples was developed to determine meropenem concentrations in human CSF in clinical settings. Meropenem in CSF samples was stabilized by mixing with 1 mol L^?1 3-morpholinopropanesulfonic acid buffer (pH 7.0) (1:1). The mixture was transferred to a Nanosep 10 K centrifugal filter device; after centrifugation, the filtrate was subjected to reversed-phase LC and the eluate was monitored at 300 nm. The retention time for meropenem was 5.8 min. The calibration curve of meropenem in human CSF was linear over 0.05–50 μg mL^?1. The intra-day and inter-day precision was 0.27–5.66 % and accuracy was 99.0–109.5 %. The limit of detection was 0.01 μg mL^?1. This method was successfully applied to neurosurgical patients, showing that it is applicable for therapeutic drug monitoring in patients receiving meropenem.     

Hydration effects on the reaction with an open-shell transition state: QM/MM-ER study for the dehydration reaction of alcohol in hot water

The reaction mechanism for the dehydration of 1,4-butanediol in hot water has been investigated by means of the hybrid quantum mechanical/molecular mechanical approach combined with the theory of energy representation (QM/MM-ER). We have assumed that the proton transfers along the hydrogen bonds of the water molecules catalyze the reaction, where the transition state (TS) forms a singlet biradical electronic structure. It has been revealed by the simulation that the biradical electronic state at the TS changes to zwitterionic structure in solution due to the hydration of the polar solvent. Such the electronic structure change gives rise to the substantial stabilization of the TS in hot water. As a result, the water-catalytic path becomes more favorable in aqueous solution than another possible path that proceeds without proton transfers as opposed to the reaction mechanism in the gas phase. Furthermore, the activation free energy computed by the present method is in excellent agreement with the experimental result.     

Quasiparticle scattering induced by charge doping of iron-pnictide superconductors probed by collective vortex pinning

Charge doping of iron-pnictide superconductors leads to collective pinning of flux vortices, whereas isovalent doping does not. Moreover, flux pinning in the charge-doped compounds is consistently described by the mean-free path fluctuations introduced by the dopant atoms, allowing for the extraction of the elastic quasiparticle scattering rate. The absence of scattering by dopant atoms in isovalently doped BaFe2(As(1-x)P(x))(2) is consistent with the observation of a linear temperature dependence of the low-temperature penetration depth in this material.     

Observation of a half step magnetization in the {Cu3}-type triangular spin ring

We report pulsed field magnetization and ESR experiments on a {Cu3} nanomagnet, where antiferromagnetically coupled Cu(2+) (S = 1/2) ions form a slightly distorted triangle. The remarkable feature is the observation of a half step magnetization, hysteresis loops, and an asymmetric magnetization between a positive and a negative field in a fast sweeping external field. This is attributed to an adiabatic change of magnetization. The energy levels determined by ESR unveil that the different mixing nature of a spin chirality of a total S = 1/2 Kramers doublet by virtue of Dzyaloshinskii-Moriya interactions is decisive for inducing half step magnetization.     

Fulde-Ferrell-Larkin-Ovchinnikov state in a perpendicular field of quasi-two-dimensional CeCoIn5

A Fulde-Ferrell-Larkin-Ovchinnkov (FFLO) state was previously reported in the quasi-2D heavy fermion CeCoIn5 when a magnetic field was applied parallel to the ab plane. Here, we conduct 115In NMR studies of this material in a perpendicular field, and provide strong evidence for FFLO in this case as well. Although the topology of the phase transition lines in the H-T phase diagram is identical for both configurations, there are several remarkable differences between them. Compared to H parallelab, the FFLO phase for H perpendicularab is confined in a much narrower region at the low-T-high-H corner in the H-T plane, and the critical field separating the FFLO and non-FFLO superconducting states almost ceases to have a temperature dependence. Moreover, directing H perpendicularab results in a notable change in the quasiparticle excitation spectrum within the planar node associated with the FFLO transition.     

Electronic and nuclear responses of fixed-in-space H2S to ultrashort intense laser fields

The Coulomb explosion dynamics of H2S, H2S3+-->H+ +S+ + H+, in ultrashort intense laser fields (12 fs, approximately 2 x 10(14) W/cm2) is studied by the coincidence momentum imaging of the three fragment ions. Different electronic and nuclear responses are identified depending on the direction of laser polarization epsilon in the molecular frame. The dependence can be interpreted in terms of the electronic and bonding characters of charge transfer states of H2S coupled to the electronic ground state.     

Efficient synthesis of N- and O-linked glycopeptides using acid-labile Boc groups for the protection of carbohydrate moieties

Development of a synthetic method for the preparation of homogeneous glycopeptides and glycoproteins is important for the elucidation of their structures and functions. Here, we report on the concise and facile synthesis of glycopeptides using Boc groups for the protection of carbohydrate hydroxyl groups. This method enables us to remove the protecting groups from peptide and carbohydrate moieties in a single-step process without undesirable any side reaction.     

AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

The need for atom‐precise biomolecule modification, and particularly the irreversible formation of covalent bonds to specific amino acids in proteins, has become an essential issue in the fields of pharmaceuticals and chemical biology. For example, antibody–drug conjugates (ADCs) are increasingly common entries into the clinical oncology pipeline. Herein, we report a new method of affinity peptide mediated regiodivergent functionalization (AJICAP?) that enables the synthesis of ADCs from native IgG antibodies. We succeeded in introducing thiol functional groups onto three lysine residues in IgGs using Fc affinity peptide reagents without antibody engineering. A cytotoxic molecule was then connected to the newly introduced thiol group, and both a surface plasmon resonance binding assay and in vivo xenograft mouse model results showed that the resulting ADC could selectively target and kill HER2‐positive cells. Our strategy provides a new approach for constructing complex antibody‐derived biomolecules.     

Effect of sintering temperature of Ce<Superscript>3+</Superscript>-doped Lu<Subscript>3</Subscript>Al<Subscript>5</Subscript>O<Subscript>12</Subscript> phosphors on light emission and properties of crystal structure for white-light-emitting diodes

The effect of the sintering temperature of Ce³⁺-doped Lu₃Al₅O₁₂ (Ce-LuAG) phosphors on the emission and properties of the crystal structure was studied. A cathodoluminescence peak at 317 nm, which was assigned to lattice defects, was exhibited in addition to emission peaks at 508 and 540 nm for the Ce-LuAG phosphors. The intensities of the 317 nm emission peak for the phosphors with mean particle diameters of 5.0 and 10.0 µm formed at a low sintering temperature of 1430 °C were higher than those for the phosphors with mean particle diameters of 18.0 and 20.5 µm formed at a high sintering temperature of 1550 °C. In contrast, the electroluminescence spectra for fabricated white-light-emitting diodes (LEDs) using the phosphors revealed that the intensity of the peak at 540 nm was strong for the mean particle diameters of 18.0 and 20.5 µm. The intensity of the 540 nm peak, which is attributed to the 4f→5d transition of the Ce³⁺ activator, showed a dependence on the sintering temperature. The relationship between the optical properties and the lattice defects is discussed.     

Inactivation Activities of Ozonated Water,Slightly Acidic Electrolyzed Water and Ethanol against SARS-CoV-2

This study aimed to compare the SARS-CoV-2-inactivation activity and virucidal mechanisms of ozonated water (OW) with those of slightly acidic electrolyzed water (SAEW) and 70% ethanol (EtOH). SARS-CoV-2-inactivation activity was evaluated in a virus solution containing 1%, 20% or 40% fetal bovine serum (FBS) with OW, SAEW or EtOH at a virus-to-test solution ratio of 1:9, 1:19 or 1:99 for a reaction time of 20 s. EtOH showed the strongest virucidal activity, followed by SAEW and OW. Even though EtOH potently inactivated the virus despite the 40% FBS concentration, virus inactivation by OW and SAEW decreased in proportion to the increase in FBS concentration. Nevertheless, OW and SAEW showed potent virucidal activity with 40% FBS at a virus-to-test solution ratio of 1:99. Real-time PCR targeting the viral genome revealed that cycle threshold values in the OW and SAEW groups were significantly higher than those in the control group, suggesting that OW and SAEW disrupted the viral genome. Western blotting analysis targeting the recombinant viral spike protein S1 subunit showed a change in the specific band into a ladder upon treatment with OW and SAEW. OW and SAEW may cause conformational changes in the S1 subunit of the SARS-CoV-2 spike protein.