Intercalation/deintercalation of solvated Mg2+ into/from graphite interlayers.

In the development of rechargeable Mg-ion batteries which are not limited by resource constraints, studies on negative electrode materials have been concentrated on efficient Mg-deposition/stripping rather than on insertion/extraction-type active materials, driven by the extremely high theoretical capacity of Mg metal (2205 mA h g-1). This work re-examined the potential of graphite, which is overlooked in electrochemical tests using a two-electrode type cell due to a large overpotential during sluggish Mg-deposition/stripping at the counter electrode caused by the passivation layer. The formation of a graphite intercalation compound (GIC) with a stage structure was demonstrated by the continual application of a constant current without considering the cut-off voltage to eliminate the detrimental impact of the counter electrode, although the intercalant was solvated Mg-ions. The GIC formed during the charging process has a blue tint just like a GIC synthesized by a vapor method. Although there is still issue with the large polarization during the deintercalation of solvated Mg ions, a reversible capacity of approximately 200 mA h g-1 could be achieved in the galvanostatic charge/discharge tests with a current density of 7.44 mA g-1. The results should facilitate future research and development of graphite as a negative electrode material.

Morphology control of zinc electrodeposition by surfactant addition for alkaline-based rechargeable batteries.

The development of Zn-air batteries with a high energy density of 1350 W h kg-1 is one of the breakthroughs required to achieve a low carbon society. However, morphology control of the Zn negative electrode during charge/discharge (Zn-deposition/stripping) is essential for practical application. Considering the manufacturing process, a simple strategy is preferable. Herein, we employed surfactants as an inhibitor of the formation of mossy and dendrite Zn structures, and studied electrochemical Zn growth from the perspective of the electric charge of the surfactant. Even by using an additive free electrolyte of 0.25 M ZnO + 4 M KOH and with 1 mM sodium dodecyl sulfate (SDS: anionic surfactant) or polyacrylic acid (PAA: non-ionic surfactant), mossy and dendrite formations were unavoidable irrespective of the current density. On the other hand, a cationic surfactant, trimethyloctadecylammonium chloride (STAC), suppressed the shape change and resulted in a smooth and dense morphology. Zeta potential measurements, kinetic current densities observed from Tafel plots, and constant potential electrolysis indicate that quaternary ammonium cations (STAC) with bulky size adsorb onto protrusions which are the cause of shape change and suppress Zn deposition in the region to promote lateral growth. Although the adsorption of STAC increased the average overvoltage for Zn-deposition/stripping in a symmetric Zn|Zn cell under a current density of 10 mA cm-2, significantly stable behavior continued for 200 h. In contrast, the overvoltage of the additive free system suddenly increased after 156 h, associated with the accumulation of insulating ZnO and Zn(OH)2 formed on the Zn surface. In charge-discharge tests using an asymmetric Cu|Zn cell, the coulombic efficiency in the additive free electrolyte was less than 95%, whereas the addition of STAC at 1 mM achieved superior cycling performance without any capacity loss originating from the generation of dead Zn (electrical isolation). These results demonstrate that the addition of STAC is a promising method of controlling the Zn morphology.

Suppressing the effect of lithium dendritic growth by the addition of magnesium bis(trifluoromethanesulfonyl)amide.

Practical applications of Li-S and Li-air batteries require the morphology of the Li metal negative electrode during charge/discharge (i.e., Li-deposition/dissolution) cycling to be precisely controlled. Herein, we used magnesium bis(trifluoromethanesulfonyl)amide [Mg(TFSA)2] as an electrolyte additive to suppress the growth of Li dendrites, utilizing the occurrence of an alloying reaction between the initially substrate-deposited Mg and the subsequently deposited Li. Notably, no metallic Mg formation and no change in Li deposition morphology were observed at an electrolyte composition of 0.1 M Mg(TFSA)2 + 0.9 M LiTFSA/triglyme, irrespective of the applied potential. In contrast, increasing the Mg salt concentration to 0.5 M resulted in the deposition of interconnected granules, reflecting a dramatic morphology improvement. X-ray diffraction analysis revealed the occurrence of the abovementioned alloying, which finally afforded a deposit composition of Li0.9Mg0.1via the formation of an intermediate Li0.14Mg0.86 phase. Importantly, the deposits obtained under various applied potentials were relatively smooth, with no needle-like morphology observed.

Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics.

Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.

A novel n-type semiconducting biomaterial.

There has been no research conducted thus far on the semiconducting behaviour of biomaterials. In this study, we present an n-type semiconducting biomaterial composed of amorphous kenaf cellulose fibre (AKCF) paper with a voltage-controlled N-type negative resistance. The AKCF generates an alternating-current wave with a frequency of 40.6 MHz from a direct-current voltage source at its threshold voltage (electric field of 5.26 kV/m), which is accompanied by a switching effect with a four-order resistance change at 293 K. This effect is attributed to the voltage-induced occurrence of strong field domains (electric double layers) at the cathode and depletion at the anode of the AKCF device. The proposed AKCF material presents considerable potential for applications in flexible/paper electronic devices such as high frequency power sources and switching effect devices.

Development of a Fully Automated Desktop Analyzer and Ultrahigh Sensitivity Digital Immunoassay for SARS-CoV-2 Nucleocapsid Antigen Detection.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has had a significant impact on public health and the global economy. Several diagnostic tools are available for the detection of infectious diseases, with reverse transcription-polymerase chain reaction (RT-PCR) testing specifically recommended for viral RNA detection. However, this diagnostic method is costly, complex, and time-consuming. Although it does not have sufficient sensitivity, antigen detection by an immunoassay is an inexpensive and simpler alternative to RT-PCR. Here, we developed an ultrahigh sensitivity digital immunoassay (d-IA) for detecting SARS-CoV-2 nucleocapsid (N) protein as antigens using a fully automated desktop analyzer based on a digital enzyme-linked immunosorbent assay. METHODS: We developed a fully automated d-IA desktop analyzer and measured the viral N protein as an antigen in nasopharyngeal (NP) swabs from patients with coronavirus disease. We studied nasopharyngeal swabs of 159 and 88 patients who were RT-PCR-negative and RT-PCR-positive, respectively. RESULTS: The limit of detection of SARS-CoV-2 d-IA was 0.0043 pg/mL of N protein. The cutoff value was 0.029 pg/mL, with a negative RT-PCR distribution. The sensitivity of RT-PCR-positive specimens was estimated to be 94.3% (83/88). The assay time was 28 min. CONCLUSIONS: Our d-IA system, which includes a novel fully automated desktop analyzer, enabled detection of the SARS-CoV-2 N-protein with a comparable sensitivity to RT-PCR within 30 min. Thus, d-IA shows potential for SARS-CoV-2 detection across multiple diagnostic centers including small clinics, hospitals, airport quarantines, and clinical laboratories.

Effect of gefitinib on warfarin antithrombotic activity.

BACKGROUND: Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib. METHODS: We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records. RESULTS: Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100). CONCLUSION: As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.

Multiple primer extension by DNA polymerase on a novel plastic DNA array coated with a biocompatible polymer.

DNA microarrays are routinely used to monitor gene expression profiling and single nucleotide polymorphisms (SNPs). However, for practically useful high performance, the detection sensitivity is still not adequate, leaving low expression genes undetected. To resolve this issue, we have developed a new plastic S-BIO PrimeSurface with a biocompatible polymer; its surface chemistry offers an extraordinarily stable thermal property for a lack of pre-activated glass slide surface. The oligonucleotides immobilized on this substrate are robust in boiling water and show no significant loss of hybridization activity during dissociation treatment. This allowed us to hybridize the templates, extend the 3' end of the immobilized DNA primers on the S-Bio by DNA polymerase using deoxynucleotidyl triphosphates (dNTP) as extender units, release the templates by denaturalization and use the same templates for a second round of reactions similar to that of the PCR method. By repeating this cycle, the picomolar concentration range of the template oligonucleotide can be detected as stable signals via the incorporation of labeled dUTP into primers. This method of Multiple Primer EXtension (MPEX) could be further extended as an alternative route for producing DNA microarrays for SNP analyses via simple template preparation such as reverse transcript cDNA or restriction enzyme treatment of genome DNA.

Electrodeposited Cu/MWCNT composite-film: a potential current collector of silicon-based negative-electrodes for Li-Ion batteries.

With the aim of developing the potential high theoretical capacity of Si as a negative electrode material for Li-ion batteries, a new type of composite current collector in which multi-walled carbon nanotubes (MWCNTs) are immobilized on a Cu surface was developed using an electroplating technique. For the Si electrode with a flat-Cu substrate, voltage plateaus related to the stepwise electrochemical lithiation were observed below 0.27 V (vs. Li/Li+), whereas the Cu/MWCNT substrate distinctly decreased the overvoltage to enhance charge/discharge capacities to approximately 1.6 times that obtained in the flat-Cu system. Field-emission scanning microscopy revealed that MWCNTs immobilized on the Cu surface extended inside the active material layer. Adhesion strength between the substrate and electrode mixture layer was reinforced by MWCNTs to increase the reversibility of change in electrode thickness before and after cycling: the expansion ratio was 200% and 134% for flat-Cu and Cu/MWCNT systems, respectively. Electrochemical impedance analysis demonstrated that MWCNTs served as an electron conduction pathway inside the electrode. By controlling the upper cutoff voltage from 2.0 V to 0.5 V, synergetic effects including improved adhesion strength and a more developed conduction pathway became noticeable: a reversible capacity of 1100 mA h g-1 with 64% capacity retention was achieved even after the 100th cycle. The results indicate that the Cu/MWCNT is a promising current collector for expansion/contraction-type active materials for rechargeable batteries.

Phase I and pharmacologic study of irinotecan and amrubicin in advanced non-small cell lung cancer.

PURPOSE: We conducted a Phase I trial of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with amrubicin, a topoisomerase II inhibitor. The aim was to determine the maximum tolerated dose (MTD) of amrubicin combined with a fixed dose of CPT-11 as well as the dose-limiting toxicities (DLT) of this combination in patients with advanced non-small cell lung cancer. PATIENTS AND METHODS: Eleven patients with stage IIIB or IV disease were treated at 3-week intervals with amrubicin (5-min intravenous injection on days 1-3) plus 60 mg/m2 of CPT-11 (90-min intravenous infusion on days 1 and 8). The starting dose of amrubicin was 25 mg/m2, and it was escalated in 5 mg/m2 increments until the maximum tolerated dose was reached. RESULTS: The 30 mg/m2 of amrubicin dose was one dose level above the MTD, since three of the five patients experienced DLT during the first cycle of treatment at this dose level. Diarrhea and leukopenia were the DLT, while thrombocytopenia was only a moderate problem. Amrubicin did not affect the pharmacokinetics of CPT-11, SN-38 or SN-38 glucuronide. Except for one patient, the biliary index on day-1 correlated well with the percentage decrease of neutrophils in a sigmoid Emax model. There were five partial responses among 11 patients for an overall response rate of 45%. CONCLUSION: The combination of amrubicin and CPT-11 seems to be active against non-small cell lung cancer with acceptable toxicity. The recommended dose for Phase II studies is 60 mg/m2 of CPT-11 (days 1 and 8) and 25 mg/m2 of amrubicin (days 1-3) administered every 21 days.

Electrochemical Na-Insertion/Extraction Property of Ni-Coated Black Phosphorus Prepared by an Electroless Deposition Method.

Electrical conductivity is one of the properties required for an active material, and it is extremely essential to exert its potential. In the present study, the strategy of coating a metal at a single particle level by an electroless deposition method was applied to enhance the cycling performance of phosphorus-based negative electrodes for Na-ion batteries. The deposition morphology and composition of the Ni coating layer were characterized by field-emission scanning electron microscopy, scanning transmission electron microscopy, and X-ray diffraction. In the 5 wt % Ni coating, an amorphous Ni layer of several nanometers thickness was homogeneously formed on the phosphorus surface, whereas a shell layer having a 200 nm thickness was formed in the order of Ni12P5, NiP2, NiP3, and metallic Ni from the surface toward the center in the 30 wt % Ni coating. Electrochemical impedance spectroscopic measurements clarified that the good electron transport proceeded throughout the developed conduction pathway to promote the phase transition to trisodium phosphide (Na3P), leading to a high reversible capacity for phosphorus; the as-prepared black phosphorus showed only a reversible capacity of 140 mA h g-1 at the 60th cycle, whereas the 30 wt % Ni-coated composite delivered a relatively high capacity of 780 mA h g(P)-1. In addition, the expansion ratio of the electrode after the 30th desodiation was the lowest among the three kinds of electrodes. By contrast, cracks and exfoliation of the active material layer from the current collector were confirmed in the as-prepared black phosphorus. These results demonstrate that the upgraded performance accomplished using the 30 wt % Ni-coated composite with the Ni/Ni-P layer is due to the synergetic effects of the electron conduction channel and a buffer matrix against a large volumetric change (∼400%) in phosphorus during the charge-discharge reactions.

[In vitro antibacterial activities of telithromycin against clinical isolates of Neisseria gonorrhoeae].

In vitro antibacterial activity of telithromycin (TEL) against the isolates of Neisseria gonorrhoeae (212 isolates) derived from urine or genital secretion in 2002 (April to December) was examined in comparison with those of macrolides (erythromycin [EM], clarithromycin [CAM]), penicillins (penicillin G [PCG]), cephems (cefodizime [CDZM], cefixime [CFIX]), quinolones (levofloxacin [LVFX]), tetracyclines (minocycline [MINO]), and aminoglycosides (spectinomycin [SPCM]). The MIC of TEL was ranged from < or = 0.039 to 0.25 microg/mL and the MIC50 and MIC90 of TEL were respectively 0.125 and 0.25 microg/mL, which were the lowest values compared with those of other oral antibacterial agents measured. When compared TEL with other agents in the order of the MIC50 and MIC90, TEL was more superior to EM and CAM (both eight times), MINO (four times and twice), and LVFX (16 and 64 times). The MIC90 of TEL was superior in twice though the MIC50 was the same in comparison with CFIX. The CDZM resistant strain did not exist and SPCM also inhibit growth with 32 microg/mL or less that was the breakpoint MIC excluding one stock though the PCG sensitive strain was only 1.4% in the injection drug. However, clinical breakpoint MIC is not established, but the efficacy of TEL is prospective because of its high antibacterial activity to inhibit growth of all stocks for gonococcus with 0.25 microg/mL. It is expected that TEL can become an oral antibiotic recommended for treatment of gonococcus if dosage and administration are considered.

[Molecular analytical evaluation of macrolide- and ketolide-resistant Streptococcus pneumoniae--mechanism of action of telithromycin and resistance to it].

PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a worldwide epidemiologic survey for investigating drug susceptibility against major bacterial pathogens in respiratory tract infections, and that is also designed to identify the action mechanism of telithromycin (TEL), a ketolide antibacterial agent, on the resistant Streptococcus pneumoniae and the resistance mechanism for TEL on the TEL-resistant S. pneumoniae strain, in addition to determine macrolide/ketolide resistant S. pneumoniae activities of TEL using molecular analysis. TEL exerted the antibacterial action on the macrolide-resistant S. pneumoniae regardless maintaining the macrolide-resistant mechanism and exhibited the potent antibacterial activity against all of ermB gene-positive strains, mefA gene-positive strains and ribosome variants. This result was considered to reflect the fact that TEL did not induce resistance to ermB and had extremely low ability to select resistant strain by mutation. These actions of TEL were considered to be derived from its novel chemical structure and might be characteristics of ketolides not possessed by macrolides. In the survey of PROTEKT in 1999 to 2002, among 13,864 strains of S. pneumoniae isolated worldwide, ketolide-resistant strain (TEL MIC > or = 4 microg/ml) was observed in 10 strains (0.07%). MIC of these 10 strains was 4 or 8 microg/mL and all of these strains were ermB-positive strains. Based on this fact, potential involvement of adenine demethylase (ermB gene product) was considered in the background of development of ketolide-resistant S. pneumoniae.

[NSAID ulcer (H. pylori, treatment, prevention)].

Although it has been reported that NSAID ulcer has been increasing in western countries, the epidemiology and treatment or prevention of this type of peptic ulcer have not been fully studied. Recently 'Guideline for the treatment of gastric ulcer' has been published in Japan. Based on the data described in the guideline, at present it is recommended to use misoprostol, protonpump inhibitor, or high dose of H2 receptor in the prevention of NSAID ulcer. In the treatment of NSAID ulcer, to stop NSAID and/or to use misoprostol or protonpump inhibitor are recommended.