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1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid pathway. Therefore, the overall objective of this study was to evaluate species-differences in glutathione (GSH) dependent in vitro metabolism of HFO-1123 in susceptible versus less susceptible species and humans as a basis for human risk assessment. Biotransformation of HFO-1123 to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH) and subsequent cysteine S-conjugate β-lyase-mediated cleavage of the corresponding cysteine conjugate (1123-CYS) was monitored in hepatic and renal subcellular fractions of mice, rats, minipigs, rabbits, and humans. While 1123-GSH formation occurred at higher rates in rat and rabbit liver S9 compared to minipig and human S9, increased β-lyase cleavage of 1123-CYS was observed in minipig kidney cytosol as compared to cytosolic fractions of other species. Increased β-lyase activity in minipig cytosol was accompanied by time-dependent formation of monofluoroacetic acid (MFA), a highly toxic compound that interferes with cellular energy production via inhibition of aconitase. Consistent with the significantly lower β-lyase activity in human cytosols, the intensity of the MFA signal in human cytosols was only a fraction of the signal obtained in minipig subcellular fractions. Even though the inconsistencies between GSH and β-lyase-dependent metabolism do not allow to draw a firm conclusion on the overall contribution of the mercapturic acid pathway to HFO-1123 biotransformation and toxicity in vivo, the β-lyase data suggest that humans may be less susceptible to HFO-1123 toxicity compared to minipigs. [ABSTRACT FROM AUTHOR]

Chiral molecules can exhibit spin-selective charge emission, which is known as chirality-induced spin selectivity1,2. Despite the constituent light elements of the molecules, their spin polarization can approach or even exceed that of typical ferromagnets. This powerful capability may lead to applications in the chiral spintronics2 field. Although the origin of spin selectivity is elusive, two microscopic phenomena have been suggested based on experimental results: effective enhancement of spin–orbit interactions3 and chirality represented by a pair of oppositely polarized spins4,5. However, the hypotheses remain to be verified. Here we report the simultaneous observation of these two phenomena in an organic chiral superconductor by magnetoresistance measurements in the vicinity of the superconducting transition temperature. A pair of oppositely polarized spins is demonstrated by spatially mapping the spin polarity in an electric alternating current excitation. The obtained spin polarization exceeds that of the Edelstein effect6–10 by several orders of magnitude, which indicates an effective enhancement of the spin–orbit interaction. Our results demonstrate a solid-state analogue of spin accumulations assumed for chiral molecules, and may provide clues to the origin of their molecular counterparts. In addition, the innovative capability of spin-current sourcing will invigorate superconducting spintronics research11.The simultaneous observation of spin–orbit interaction enhancement and chirality represented by a pair of oppositely polarized spins is reported for an organic chiral superconductor in the vicinity of the superconducting transition temperature. [ABSTRACT FROM AUTHOR]

In this work, the problem of radiation scattering by ice crystals typical for cirrus clouds is solved for a 94-GHz radar (wavelength 3189 µm) and a lidar (wavelength 0.355 µm); the ice refractive indices are 1.7864 + 0.0032i and 1.3249 + 0i, respectively. The scattering matrices are calculated within the physical optics approximation and the discrete dipole approximation for the case of randomly oriented particles with sizes from 4 to 1000 µm. The ratio of the radar and lidar backscattering signals in the backward direction (the so-called radar–lidar ratio) is calculated for a wide range of the particle size for typical shapes of cirrus cloud ice crystals. It is shown that this ratio can be used for estimating the size of ice crystals in cirrus clouds. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123)" published in the Archives of Toxicology. The correction addresses an error in the presentation of Figure 5 in the original article. The corrected figure shows the identification of species-differences in the formation of certain metabolites in minipigs, rabbits, and humans. The correction is provided by multiple authors. Springer Nature, the publisher, remains neutral in terms of jurisdictional claims and institutional affiliations. [Extracted from the article]

Ultrafast electronic-phase change in solids by light, called photoinduced phase transition, is a central issue in the field of non-equilibrium quantum physics, which has been developed very recently. In most of those phenomena, charge or spin orders in an original phase are melted by photocarrier generations, while an ordered state is usually difficult to be created from a non-ordered state by a photoexcitation. Here, we demonstrate that a strong terahertz electric-field pulse changes a Mott insulator of an organic molecular compound in κ-(ET)2Cu[N(CN)2]Cl (ET = bis(ethylenedithio)tetrathiafulvalene), to a macroscopically polarized charge-order state; herein, electronic ferroelectricity is induced by the collective intermolecular charge transfers in each dimer. In contrast, in an isostructural compound, κ-(ET)2Cu2(CN)3, which shows the spin-liquid state at low temperatures, a similar polar charge order is not stabilized by the same terahertz pulse. From the comparative studies of terahertz-field-induced second-harmonic-generation and reflectivity changes in the two compounds, we suggest the possibility that a coupling of charge and spin degrees of freedom would play important roles in the stabilization of polar charge order. Photoinduced phase transition is a central issue in the field of non-equilibrium quantum physics. Here, the authors demonstrate that a terahertz electric-field pulse changes a Mott insulator of an organic molecular compound to a macroscopically polarized charge-order state. [ABSTRACT FROM AUTHOR]

The article focuses on a comprehensive collection of alloy phase diagrams for the binary systems. It presents the Silver-Lithium (Ag-Li) phase diagram based on the works wherein the (Ag) liquidus and solidus were assessed thermodynamically. It also highlights the Carbon-Manganese (C-Mn) phase diagram obtained through thermodynamic assessments.

Several diagrams is presented which explains the binary phase diagrams of alloys including silver-ytterbium (Ag-Yb), aluminum-cobalt (Al-Co), and aluminum-iodine (Al-I).

An Erratum to this paper has been published: https://doi.org/10.1134/S1024856023330023 [ABSTRACT FROM AUTHOR]

The article presents several updates on various alloy phase diagrams for binary systems. Topics discussed include the disagreement or inconsistencies among the thermodynamic models of boron-iron (B-FE) phase diagram, the thermodynamic assessment for the chromium-zirconium (Cr-Zr) phase diagram, and the phase diagram for the germanium-nickel (Ge-Ni) phase diagram.

The article offers information on Binary Alloy Phase Diagrams, a collection of alloy phase diagrams for 2159 binary systems and the recent information presents binary phase diagrams for various chemical alloys. These include Aluminium-Neodymium (Al-Nd) phase diagram, Aluminum-Vanadium (Al-V) phase diagram and Bismuth-Ytterbium (Bi-Yb) binary phase diagram.

The article discusses a review of binary phase diagrams designed to provide information on the binary phase diagrams for the Ag-Cl, Br-Pb, Br-Zn, C-Cu, Ce-Zr, Cl-Zn, Fe-Lu, Fe-Tm, Ga-V, Nd-Ti, Nd-Zr and Si-Ta systems that became available after 1990. The criteria for the selection of information for inclusion in the review are systems where no phase diagram was given in, complete diagrams substantially different from earlier version and partial diagrams that alter earlier version.

Solutions of a nonlinear heat equation are numerically computed in the time variable t lying in the complex plane, and possible singularities are sought. It turns out that in the complex half plane $$ \{ \mathfrak {R}[t] \ge 0 \}$$ , where $$\mathfrak {R}$$ denotes the real part of a complex number, there is no singularity other than that which exists on the real line. However, if we compute further in the Riemann surface, new singularities are found. A certain nonlinear Schrödinger equation which is associated with our problem is also computed numerically and we propose a conjecture that it is well-posed globally in time. [ABSTRACT FROM AUTHOR]

The article presents a supplemental literature review of binary phase diagrams. This review checked the thermodynamic consistency of the phase diagrams based on phase rules, including the B-La phase diagram, the B-Zn phase diagram and the Bi-La diagram. It also added reaction tables and crystal structure data.

The compact non-neutral plasma trap systems named 'S-POD' have been developed at Hiroshima University as an experimental simulator of beam dynamics. S-POD is based either on a linear Paul trap or on a Penning trap and can approximately reproduce the collective motion of a relativistic charged-particle beam observed in the center-of-mass frame. We here employ the Paul trap system to investigate the behavior of an ion plasma near a dipole resonance. A simple method is proposed to calibrate the data of secular frequency measurements by using the dipole instability condition. We also show that the transverse density profile of an ion plasma in the trap can be estimated from the time evolution of ion losses caused by the resonance. [ABSTRACT FROM AUTHOR]

The article discusses the supplemental literature review of binary phase diagrams of alloys. Topics include the thermodynamical analysis of new phase diagrams, reaction tables, and crystal structure data. Presented phase diagrams of alloys includes gold-cerium (Au-Ce), boron-praseodymium (B-Pr), and bismuth-gadolinium (Bi-Gd).

The article presents the alloy phase diagrams for several binary systems including aluminum-magnesium (Al-Mg), bismuth-strontium (Bi-Sr) and cerium-copper (Ce-Cu). Tables that depict the crystal structure data of the binary systems are given. The criteria for the selection of information for inclusion in the supplemental literature review of the binary phase diagrams are also mentioned.

Several binary phase diagrams of alloys are presented including silver-cobalt phase diagram based on thermodynamic modeling, silver-erbium phase diagram, and silver-palladium phase diagram based on data using differential scanning calorimetry and Knudsen cell mass spectrometry.

Background: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level.Methods: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA.Results: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells.Conclusions: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy. [ABSTRACT FROM AUTHOR]

The article offers information on the binary phase diagrams of Silver-Holmium, Silver-Terbium and Cadmium-Sodium. Topics discussed include thermodynamic consistency of the new phase diagrams was checked based on phase rules and calculated phase diagram comparison to the old phase diagram with respect to the features including liquidus, solidus and allotropic transformations of constituent elements.

The article offers information on the binary phase diagrams of aluminum-bromine, boron-cadmium and cadmium-magnesium. Topics discussed include thermodynamic consistency of the new phase diagrams was checked based on phase rules and calculated phase diagram comparison to the old phase diagram with respect to the features including liquidus, solidus and allotropic transformations of constituent elements.

The article focuses on binary alloy phase diagrams. It discusses diagrams including Ag (silver)-Ni (nickel), Al (aluminum)-Cu (copper), and Al (aluminum) -Sc (scandium) phase diagrams. Several diagrams of weight percent of iridium, carbon, and scandium and tables showing crystal structure data for Ag-Ni, Al-Cu, and Al-Sc are also presented.

Background:We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II-IIIA non-small cell lung cancer.Methods:Patients received three cycles of docetaxel (60 mg m−2) plus cisplatin (80 mg m−2) and then received S-1 (40 mg m−2 twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients.Results:One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%).Conclusion:The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance. [ABSTRACT FROM AUTHOR]

We fabricated and investigated a plasmonic racetrack resonator with a trench structure. Trench channel plasmon polaritons excited by end-fire coupling at a wavelength of 633 nm are observed in the fabricated racetrack resonator. The racetrack resonator also worked as a plasmonic racetrack resonator. The experimental and simulation results of the electric field distributions are in good agreement. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to establish the maximum tolerated dose of concurrent chemoradiotherapy (cCRT) with conventional administration of the docetaxel (D) plus cisplatin (P) (conv-DP) regimen.Methods: Patients (aged ≤70 years) with unresectable dry stage III non-small-cell lung cancer (NSCLC) and having performance status 0 or 1 and adequate organ function were eligible. They received radiotherapy (60 Gy in 30 fractions) once daily starting on day 2. Concurrent P (day 1; 60 mg/m(2) at Levels 1-3, 80 mg/m(2) at Level 4) and D (day 1; 30 mg/m(2) at Level 1, 40 mg/m(2) at Level 2, 50 mg/m(2) at Levels 3-4) were administered every 4 weeks for 2-4 courses.Results: Eighteen patients were enrolled (stage IIIA/IIIB, 5/13 patients). Three cases of dose-limiting toxicity were observed in this study, although another 3 cases were added at Levels 2 and 3. Radiotherapy was completed in 15 patients. Seventeen patients received more than 2 courses of chemotherapy. Neither Grade 3/4 esophagitis nor severe hematological events were observed at Levels 1-4. However, dose escalation to Level 5 (P [80 mg/m(2)], D [60 mg/m(2)]) was stopped because the Level 5 dose was the recommended dose (RD) of chemotherapy alone for stage IIIB/IV NSCLC in Japan. Therefore, the RD was determined as D50/P80 mg/m(2) in this cCRT. The objective response rate was 89%, and the median survival time was 23.6 months.Conclusions: cCRT with non-split DP was a tolerable and effective regimen, and RD was 50/80 mg/m(2) every 4 weeks. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the risk of common peroneal nerve injury in FM drilling as compared to transtibial drilling in anatomical double-bundle ACL reconstruction. Methods: Ten cadaveric knees without ligament injury or significant arthritis were used for this study. Knees were secured at 90° and 120° of flexion. In transtibial drilling groups, a guide pin was drilled through either the anteromedial bundle (AMB) or posterolateral bundle (PLB) tibial insertion site to either the AMB or PLB femoral insertion site (tibial insertion site-femoral insertion site: AM-AM, PL-PL, PL-AM and AM-PL). In FM drilling groups (FM-AM and FM-PL),the pin was drilled at the AMB or PLB femoral insertion site through the FM. We measured the shortest distance between the point at which the pin ran through the lateral cortex of the femur and the ipsilateral common peroneal nerve at a knee flexion of 90° and 120°. Results: At a knee flexion of 90°, the shortest mean distance to the common peroneal nerve was 15.3 mm in the FM-PL group, 13.4 mm in the FM-AM group, 27.9 mm in the PL-PL group, 30.8 mm in the AM-AM group, 37.8 mm in the PL-AM group and 29.5 mm in the AM-PL group. At a knee of flexion 120°, the mean distance was 17.3 mm in the FM-PL group, 18.1 mm in the FM-AM group, 32.2 mm in the PL-PL group, 36.6 mm in the AM-AM group, 38.0 mm in the PL-AM group and 35.2 mm in the AM-PL group. Significant differences were observed between 90° and 120° of knee flexion in the FM-AM, PL-PL, AM-AM and AM-PL groups ( P < 0.05).Significant differences were observed at flex 90° between the FM-AM group and AM-AM group, and between the FM-AM group and PL-AM group. Significant differences were observed at flex 120° between the FM-AM group and AM-AM group, between the FM-AM group and PL-AM group and between the FM-PL group and AM-PL group. Conclusion: The distance to the peroneal nerve in FM drilling was significantly longer at 120° than at 90° of knee flexion. Therefore, the risk of peroneal injury using FM drilling should decrease at a higher angle of knee flexion. [ABSTRACT FROM AUTHOR]

Photonic cavities have emerged as an indispensable tool to control and manipulate harmonic motion in opto/electromechanical systems. Invariably, in these systems a high-quality-factor photonic mode is parametrically coupled to a high-quality-factor mechanical oscillation mode. This entails the demanding challenges of either combining two physically distinct systems, or else optimizing the same nanostructure for both mechanical and optical properties. In contrast to these approaches, here we show that the cavity can be realized by the second oscillation mode of the same mechanical oscillator. A piezoelectric pump generates strain-induced parametric coupling between the first and the second mode at a rate that can exceed their intrinsic relaxation rate. This leads to a mechanically induced transparency in the second mode which plays the role of the phonon cavity, the emergence of parametric normal-mode splitting and the ability to cool the first mode. Thus, the mechanical oscillator can now be completely manipulated by a phonon cavity. [ABSTRACT FROM AUTHOR]

The lattice parameters of a Nd 1111 Fe-pnictide superconductor, NdFeAsOF, were accurately measured using X-ray diffraction between 20 K and 280 K. A very small change in the lattice parameter could be detected in the superconducting phase. This change can be attributed to a spontaneous strain generated in the superconducting phase by the coupling between a superconducting order parameter and the strain. The present results are compared with the thermal expansion coefficients of Ba (FeCo)As, in addition to the previous lattice parameter measurements of YBaCuO, MgB, LaSrCuO, and BaKBiO. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The activation of platelet-derived growth factor receptor-β (PDGFR-β) signalling is increased in the glomeruli and tubules of diabetic animals. In this study, we examined the role of PDGFR-β signalling during the development of diabetic nephropathy. Methods: We recently generated pancreatic beta cell-specific Ca/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice (CaMKIIα mice), which show very high plasma glucose levels up to 55.5 mmol/l and exhibit the features of diabetic nephropathy. These mice were crossed with conditional knockout mice in which Pdgfr-β (also known as Pdgfrb) was deleted postnatally. The effect of the deletion of the Pdgfr-β gene on diabetic nephropathy in CaMKIIα mice was evaluated at 10 and 16 weeks of age. Results: The plasma glucose concentrations and HbA levels were elevated in the CaMKIIα mice from 4 weeks of age. Variables indicative of diabetic nephropathy, such as an increased urinary albumin/creatinine ratio, kidney weight/body weight ratio and mesangial area/glomerular area ratio, were observed at 16 weeks of age. The postnatal deletion of the Pdgfr-β gene significantly decreased the urinary albumin/creatinine ratio and mesangial area/glomerular area ratio without affecting the plasma glucose concentration. Furthermore, the increased oxidative stress in the kidneys of the CaMKIIα mice as shown by the increased urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the increased expression of NAD(P)H oxidase 4 (NOX4), glutathione peroxidase 1 (GPX1) and manganese superoxide dismutase (MnSOD) was decreased by Pdgfr-β gene deletion. Conclusions/interpretation: The activation of PDGFR-β signalling contributes to the progress of diabetic nephropathy, with an increase in oxidative stress and mesangial expansion in CaMKIIα mice. [ABSTRACT FROM AUTHOR]

The kinetics of diethyl dithiophosphate adsorption on chalcopyrite and tennantite has been studied by UV-visible spectroscopy at pH values of 4, 6, and 9. The concentration of diethyl dithiophosphate in the solution has been monitored as a function of time and pH for both minerals. It was found that the adsorption tendency of diethyl dithiophosphate on both minerals decreased with the increasing pH treatments. This is due to the existence of metal hydroxide species onto the mineral surface in more alkaline condition inhibiting the adsorption of diethyl dithiophosphate species. In comparison to that of chalcopyrite, tennantite possessed slightly higher adsorption of diethyl dithiophosphate in acid condition, while vice versa correlation observed at other pH treatments at where the coverage of metal hydroxide species obtained higher than that of chalcopyrite showing that the rate oxidation of tennantite is higher. An adsorption mechanism has been proposed and tested against the experimental kinetic data. Both the kinetic data and flotation studies are consistent with the proposed mechanism. [ABSTRACT FROM AUTHOR]

Competition between electron localization and delocalization in Mott insulators underpins the physics of strongly correlated electron systems. Photoexcitation, which redistributes charge, can control this many-body process on the ultrafast timescale. So far, time-resolved studies have been carried out in solids in which other degrees of freedom, such as lattice, spin or orbital excitations, dominate. However, the underlying quantum dynamics of 'bare' electronic excitations has remained out of reach. Quantum many-body dynamics are observed only in the controlled environment of optical lattices where the dynamics are slower and lattice excitations are absent. By using nearly single-cycle near-infrared pulses, we have measured coherent electronic excitations in the organic salt ET-F2TCNQ, a prototypical one-dimensional Mott insulator. After photoexcitation, a new resonance appears, which oscillates at 25 THz. Time-dependent simulations of the Mott-Hubbard Hamiltonian reproduce the oscillations, showing that electronic delocalization occurs through quantum interference between bound and ionized holon-doublon pairs. [ABSTRACT FROM AUTHOR]

Partially fluorinated metal oxides were studied for manufacturing dichloropentafluoropropanes (CF3CF2CHCl2 and CCl2FCF2CHClF) and controlling the selectivity of their isomers. When activated by elemental fluorine or dichlorodifluoromethane, metal oxides such as TiO2, HfO2, Al2O3, and ZrO2, exhibited catalytic activity in the reaction of dichlorofluoromethane with tetrafluoroethylene. In the case of the TiO2 catalyst, the more fluorine incorporated, the higher the selectivity was for the CCl2FCF2CHClF formation. The fluorine-activated TiO2 catalyst was identified by XRD and XPS as a mixture of TiO2 and partially fluorinated TiO2 including TiOF2. [ABSTRACT FROM AUTHOR]

Full-scale three-dimensional (3D) models offer a useful tool in preoperative planning, allowing full-scale stereoscopic recognition from any direction and distance with tactile feedback. Although skills and implants have progressed with various innovations, rheumatoid cervical spine surgery remains challenging. No previous studies have documented the usefulness of full-scale 3D models in this complicated situation. The present study assessed the utility of full-scale 3D models in rheumatoid cervical spine surgery. Polyurethane or plaster 3D models of 15 full-sized occipitocervical or upper cervical spines were fabricated using rapid prototyping (stereolithography) techniques from 1-mm slices of individual CT data. A comfortable alignment for patients was reproduced from CT data obtained with the patient in a comfortable occipitocervical position. Usefulness of these models was analyzed. Using models as a template, appropriate shape of the plate-rod construct could be created in advance. No troublesome Halo-vests were needed for preoperative adjustment of occipitocervical angle. No patients complained of dysphasia following surgery. Screw entry points and trajectories were simultaneously determined with full-scale dimensions and perspective, proving particularly valuable in cases involving high-riding vertebral artery. Full-scale stereoscopic recognition has never been achieved with any existing imaging modalities. Full-scale 3D models thus appear useful and applicable to all complicated spinal surgeries. The combination of computer-assisted navigation systems and full-scale 3D models appears likely to provide much better surgical results. [ABSTRACT FROM AUTHOR]

Recent clinical trials have clearly demonstrated that the administration with β-blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of β-blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to β-blockers among 80 patients with CHF owing to idiopathic dilated cardiomyopathy. The polymorphisms of NET T-182C (P=0.019), ADRA1D T1848A (P=0.023) and ADRA1D A1905G (P=0.029) were associated with the improvement of left ventricular fractional shortening (LVFS) by β-blockers. Furthermore, combined genotype analysis of NET T-182C and ADRA1D T1848A revealed a significant difference in LVFS improvement among genotype groups (P=0.011). These results suggest that NET (T-182C) and ADRA1D (T1848A and A1905G) polymorphisms are predictive markers of the response to β-blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the β-blocker therapy in CHF.The Pharmacogenomics Journal (2008) 8, 78–84; doi:10.1038/sj.tpj.6500450; published online 3 April 2007 [ABSTRACT FROM AUTHOR]

Recently, we identified a novel human virus with a circular DNA genome of 3.2 kb, tentatively designated as torque teno midi virus (TTMDV), with a genomic organization resembling those of torque teno virus (TTV) of 3.8–3.9 kb and torque teno mini virus (TTMV) of 2.8–2.9 kb. To investigate the extent of genomic variability of TTMDV genomes, the full-length sequence was determined for 15 TTMDV isolates obtained from viremic individuals in Japan. The 15 TTMDV isolates comprised 3175–3230 bases and shared 67.0–90.3% identities with each other, and were only 68.4–73.0% identical to the 3 reported TTMDV isolates over the entire genome. TTMDV possessed a genomic organization with four open reading frames (ORF1–ORF4) with characteristic sequence motifs and stem and loop structures with high GC content, similar to TTV and TTMV. The total of 18 TTMDV genomes differed by up to 60.7% from each other in the amino acid sequence of ORF1 (658–677 amino acids), but segregated phylogenetically into the same cluster, which was distantly related to the TTVs and TTMVs. These results indicate that TTMDV with a circular DNA genome of 3.2 kb, has an extremely high degree of genomic variability, and is classifiable into a third group in the genus Anellovirus. [ABSTRACT FROM AUTHOR]

Effects of using ZnO:Al (AZO) transparent conducting oxide films on the performance of the hydrogenated amorphous Si (a-Si:H) solar cells are studied. AZO films are prepared by the sol-gel method. Rapid thermal annealing (RTA) in vacuum of these films results in a decrease in resistivity. AZO films exhibit a high transmittance in the visible region and excellent resistance against hydrogen radical exposure. The light-trapping effect is proven by a measured decrease in the transmittance and reflectance spectra of the textured AZO/glass structure with a RMS roughness of 67.5 nm. It is concluded that highly textured AZO/glass structures enhance the photocurrent in a-Si:H-based thin film solar cells. [ABSTRACT FROM AUTHOR]

Hepatitis E is rare in Japan but is occurring more frequently than previously thought. To investigate whether de novo subclinical infection of hepatitis E virus (HEV) has recently increased in Japan, HEV RNA was assayed in serum samples obtained from 4019 Japanese voluntary blood donors with alanine aminotransferase (ALT) of ≥61 IU/l, who are likely to have ongoing HEV infection, during 1991–2006. The overall rates of IgG-class antibody to HEV (anti-HEV IgG), anti-HEV IgM/IgA and HEV RNA among 3185 donors in 2004–2006 were comparable with those among 594 donors in 1998 (5.3 vs. 5.2%, 0.2 vs. 0.5%, and 0.2 vs. 0.3%, respectively). Among blood donors with ALT ≥ 201 IU/l in three groups according to the year of blood collection (1991–1995 [ n = 156], 1996–1999 [ n = 116] and 2004–2006 [ n = 61]), there were no appreciable differences in the prevalence of anti-HEV IgG (5.8, 4.3, and 6.6%, respectively), anti-HEV IgM/IgA (1.9, 3.4, and 3.3%, respectively) and HEV RNA (1.3, 3.4, and 3.3%, respectively). The eleven HEV isolates obtained in the present study differed from each other by 1.7–22.8% in the ORF2 sequence and segregated into genotype 3 or 4. The occurrence rate of subclinical infection with divergent HEV strains has essentially remained unchanged during 1991–2006 in Japan. [ABSTRACT FROM AUTHOR]

The interaction between viral capsid proteins and specific molecules exposed on the plasma membrane of the cells is involved in the viral tropism. A human adenovirus (Ad) belonging to subgroups A, C, D, E and F infects cells via the interaction between the fiber knob and the primary receptor, the coxsackievirus and adenovirus receptor (CAR). Conventional human adenovirus type 5 (hAd5) vectors show efficient transduction in CAR-positive cells; in contrast, hAd5 vector application is limited by poor transduction into cells lacking CAR expression. In the present study, to broaden the tropism of hAd5 vectors, we generated hAd5 vectors containing the TAT peptide, which is a protein transduction domain derived from human immunodeficiency virus, in the HI loop of the fiber knob (Ad-TAT(HI)-L2) or the C-terminus of the fiber knob (Ad-TAT(C)-L2). In CAR-negative adherent cells, Ad-TAT(HI)-L2 and Ad-TAT(C)-L2 showed approximately 50- to 500-fold higher gene expression than the conventional hAd5 vector (Ad-L2). Ad-TAT(HI)-L2 was also more efficient than Ad-L2 in blood cell lines and in two types of primary cultured human vascular smooth muscle cells, which are almost refractory to Ad-L2. Furthermore, Ad-TAT(HI)-L2 was more efficient than other types of fiber-modified Ad vectors, which harbor an RGD (Arg-Gly-Asp) or a poly-lysine (KKKKKKK;K7) peptide in the HI loop or the C-terminus of the fiber knob, respectively. Ad-TAT(HI)-L2 efficiently transduced the organs in levels and patterns that were roughly similar to those of Ad-L2 after being systemically injected into mice. To the best of our knowledge, this study is the first report showing that hAd5 vectors containing the TAT peptide in the fiber knob could efficiently transduce cells independently of CAR. These Ad vectors should be useful for gene functional analysis and gene therapy.Gene Therapy (2007) 14, 1160–1165; doi:10.1038/sj.gt.3302969; published online 17 May 2007 [ABSTRACT FROM AUTHOR]

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age 70 and performance status 0–2, or age <70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m−2 IV on days 1–3. The SPE arm received cisplatin 25 mg m−2 IV on days 1–3 and etoposide 80 mg m−2 IV on days 1–3. Both regimens were given with granulocyte colony-stimulating factor support in a 21–28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3–4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P=0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk–benefit balance.British Journal of Cancer (2007) 97, 162–169. doi:10.1038/sj.bjc.6603810 www.bjcancer.com Published online 19 June 2007 [ABSTRACT FROM AUTHOR]

Although the potential significance of hepatitis B surface antigen (HBsAg) mutants for failure of immunization has been studied in some endemic countries, whether the “a” determinant variants are responsible for vaccine failure in Mongolia remains unknown. Fifty-nine HBsAg-positive children (age: 8.8 ± 0.9 years) who had been observed during the nationwide survey of vaccinated cohorts conducted in 2004 were subjected to molecular analyses of hepatitis B virus (HBV). Partial S gene sequences encoding amino acids (aa) 40–171 of HBsAg were determined in 57 children (96.6%) who had detectable HBV DNA. Phylogenetic analysis of the S gene sequences revealed that genotype D accounted for 93.0% and genotype A for 5.3%. Only one child (1.7%) had HBVs of genotypes A and D. HBsAg mutations were found in 17 (29.8%) children ranging from 1 to 4 aa per subject (mean ± SD, 1.6 ± 0.9 aa). Pro127Thr and Thr118Ala were the most common substitutions, which occurred in 6 (10.5%) and 3 (5.3%) subjects, respectively; none had Gly145Arg. There were no significant associations in the prevalence of HBsAg mutations with age, sex, residential area, or vaccination status against hepatitis B. Analysis of the deduced amino acid sequence of the entire preS1/preS2/S gene revealed that eight genotype D isolates and one genotype A isolate were quite similar to previously-reported wild-type isolates, suggesting that they are essentially wild-type, but not vaccine-induced mutants. In conclusion, the results demonstrate that hepatitis B surface gene mutants do not play a significant role in vaccination failure in Mongolia. [ABSTRACT FROM AUTHOR]

Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.Oncogene (2007) 26, 349–359. doi:10.1038/sj.onc.1209799; published online 14 August 2006 [ABSTRACT FROM AUTHOR]

Non-neutral plasmas composed of 106 to 107 Ar + ions were confined in a linear Paul trap which had a non-harmonic electrostatic potential in axial direction. Axial resonances were observed by applying additional RF electric field and detecting axially ejected ions. It was found that the resonance frequencies shifted as a function of the ion number, the amplitude of additional RF electric field, and the applied electrostatic potential for the axial confinement. [ABSTRACT FROM AUTHOR]

The expression of IFNβ in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNβ on Reg expression, and the implications of this in terms of autoimmunity. Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNβ mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNβ on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. Reg2 was upregulated in islets from the NOD RIP-HuIFNβ mice at the onset of the autoimmune attack. IFNβ upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNβ. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNβ-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes. [ABSTRACT FROM AUTHOR]