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When laser radiation is skilfully applied, atoms and molecules can be cooled1–3, allowing the precise measurements and control of quantum systems. This is essential for the fundamental studies of physics as well as practical applications such as precision spectroscopy4–7, ultracold gases with quantum statistical properties8–10 and quantum computing. In laser cooling, atoms are slowed to otherwise unattainable velocities through repeated cycles of laser photon absorption and spontaneous emission in random directions. Simple systems can serve as rigorous testing grounds for fundamental physics—one such case is the purely leptonic positronium11,12, an exotic atom comprising an electron and its antiparticle, the positron. Laser cooling of positronium, however, has hitherto remained unrealized. Here we demonstrate the one-dimensional laser cooling of positronium. An innovative laser system emitting a train of broadband pulses with successively increasing central frequencies was used to overcome major challenges posed by the short positronium lifetime and the effects of Doppler broadening and recoil. One-dimensional chirp cooling was used to cool a portion of the dilute positronium gas to a velocity distribution of approximately 1 K in 100 ns. A major advancement in the field of low-temperature fundamental physics of antimatter, this study on a purely leptonic system complements work on antihydrogen13, a hadron-containing exotic atom. The successful application of laser cooling to positronium affords unique opportunities to rigorously test bound-state quantum electrodynamics and to potentially realize Bose–Einstein condensation14–18 in this matter–antimatter system.The one-dimensional laser cooling of positronium enables testing of quantum electrodynamics and could realize Bose–Einstein condensation in positronium. [ABSTRACT FROM AUTHOR]

Injecting high-energy heavy ions in the electronic stopping regime into solids can create cylindrical damage zones called latent ion tracks. Although these tracks form in many materials, none have ever been observed in diamond, even when irradiated with high-energy GeV uranium ions. Here we report the first observation of ion track formation in diamond irradiated with 2–9 MeV C60 fullerene ions. Depending on the ion energy, the mean track length (diameter) changed from 17 (3.2) nm to 52 (7.1) nm. High resolution scanning transmission electron microscopy (HR-STEM) indicated the amorphization in the tracks, in which π-bonding signal from graphite was detected by the electron energy loss spectroscopy (EELS). Since the melting transition is not induced in diamond at atmospheric pressure, conventional inelastic thermal spike calculations cannot be applied. Two-temperature molecular dynamics simulations succeeded in the reproduction of both the track formation under MeV C60 irradiations and the no-track formation under GeV monoatomic ion irradiations. While high-energy heavy ions create cylindrical damage zones called ion tracks in many materials, diamond was an exception for a long time. The authors have succeeded in creating the ion tracks in diamond utilizing 2−9MeV C60 fullerene ion irradiation and studied the structure of the tracks. [ABSTRACT FROM AUTHOR]

Cellulose nanofibers (CNFs), which are plant-derived materials, have recently garnered considerable attention owing to their excellent mechanical properties, such as their low weight and high Young's modulus. Novel methods for producing 100% CNF bulk structural materials have been developed. However, the tribological properties of CNFs have not been investigated thus far although their mechanical properties are known and are comparable to those of some conventional structural materials. In this study, the tribological properties of a novel biomass material, 100% CNF molding, were investigated based on CNF/steel contacts under dry and boundary lubrication conditions at various temperatures. The friction test results showed that the friction coefficient and wear volume of the CNF molding increased with the test temperature of the CNF/steel tribopair under dry-sliding conditions. Conversely, no significant temperature dependence of the friction and wear properties was observed upon lubrication with a pure polyalfaolefin. The surface analytical results revealed that the amorphization of the CNF molding progressed on the worn surface, especially under dry-sliding conditions at a high temperature. All the results suggested that the friction and wear performance of the 100% CNF moldings strongly depends on the sliding test conditions, and the amorphization process of the CNF molding can affect its friction and wear performance. [ABSTRACT FROM AUTHOR]

Consider an oriented curve Γ in a domain D in the plane R 2 . Thinking of D as a piece of paper, one can make a curved folding in the Euclidean space R 3 . This can be expressed as the image of an "origami map" Φ : D → R 3 such that Γ is the singular set of Φ , the word "origami" coming from the Japanese term for paper folding. We call the singular set image C : = Φ (Γ) the crease of Φ and the singular set Γ the crease pattern of Φ . We are interested in the number of origami maps whose creases and crease patterns are C and Γ , respectively. Two such possibilities have been known. In the authors' previous work, two other new possibilities and an explicit example with four such non-congruent distinct curved foldings were established. In this paper, we determine the possible values for the number N of congruence classes of curved foldings with the same crease and crease pattern. As a consequence, if C is a non-closed simple arc, then N = 4 if and only if both Γ and C do not admit any symmetries. On the other hand, when C is a closed curve, there are infinitely many distinct possibilities for curved foldings with the same crease and crease pattern, in general. [ABSTRACT FROM AUTHOR]

We demonstrate a new operation mode of thermal gas sensor based on thermal capacity extraction with identification algorithm. The system is a silicon microstructure covered with zeolites operated at constant temperature while stimulated by heat pseudo-random sequence. The proposed detection principle is demonstrated at room temperature and atmospheric pressure through the detection of gas water molecules with an hydrophilic FAU-type zeolite coating. The identification algorithm is a continuous-time closed-loop identification algorithm based on the instrumental variable principle. [ABSTRACT FROM AUTHOR]

The RILEM AAR-13 test procedure is not a test method by itself; rather it is a procedure applying alkali wrapping to concrete prisms during test exposure to assess the expansion potential of alkali-silica reaction. When combined with procedures of other test methods, for example AAR-10 or AAR-11, it becomes a full test procedure. The wrapping procedure described was originally proposed by a technical committee of the Japan Concrete Institute "Technical Committee on Performance Based Design and Maintenance Scenario with Controlling ASR Deterioration". The procedure includes a detailed description of the materials to be used for wrapping, procedures for calculation of alkalinity of the solution that aims to simulate the pore solution of the concrete prism depending on the alkali content of the concrete, and finally specific procedures for storage and measurements of the prisms. The procedure of calculating the alkalinity of the solution to be applied for the wrapping is assumed to be conservative because no subtraction is made for assumed alkali binding by the hydrates or alkali absorption by the aggregates. The alkali content is estimated by adding the alkali contribution from all concrete constituents (except the aggregates) including the supplementary cementitious materials (SCMs). [ABSTRACT FROM AUTHOR]

Since the first experimental observation of all-optical switching phenomena, intensive research has been focused on finding suitable magnetic systems that can be integrated as storage elements within spintronic devices and whose magnetization can be controlled through ultra-short single laser pulses. We report here atomistic spin simulations of all-optical switching in multilayered structures alternating n monolayers of Tb and m monolayers of Co. By using a two temperature model, we numerically calculate the thermal variation of the magnetization of each sublattice as well as the magnetization dynamics of [ Tb n / Co m ] multilayers upon incidence of a single laser pulse. In particular, the condition to observe thermally-induced magnetization switching is investigated upon varying systematically both the composition of the sample (n,m) and the laser fluence. The samples with one monolayer of Tb as [ Tb 1 / Co 2 ] and [ Tb 1 / Co 3 ] are showing thermally induced magnetization switching above a fluence threshold. The reversal mechanism is mediated by the residual magnetization of the Tb lattice while the Co is fully demagnetized in agreement with the models developed for ferrimagnetic alloys. The switching is however not fully deterministic but the error rate can be tuned by the damping parameter. Increasing the number of monolayers the switching becomes completely stochastic. The intermixing at the Tb/Co interfaces appears to be a promising way to reduce the stochasticity. These results predict for the first time the possibility of TIMS in [Tb/Co] multilayers and suggest the occurrence of sub-picosecond magnetization reversal using single laser pulses. [ABSTRACT FROM AUTHOR]

Calabi and Cheng-Yau's Bernstein-type theorem asserts that an entire zero mean curvature graph in Lorentz–Minkowski (n + 1) -space R 1 n + 1 which admits only space-like points is a hyperplane. Recently, the third and fourth authors proved a line theorem for hypersurfaces at their degenerate light-like points. Using this, we give an improvement of the Bernstein-type theorem, and we show that an entire zero mean curvature graph in R 1 n + 1 consisting only of space-like or light-like points is a hyperplane. This is a generalization of the first, third and fourth authors' previous result for n = 2 . [ABSTRACT FROM AUTHOR]

Damaged regions of cylindrical shapes called ion tracks, typically in nano-meters wide and tens micro-meters long, are formed along the ion trajectories in many insulators, when high energy ions in the electronic stopping regime are injected. In most cases, the ion tracks were assumed as consequences of dense electronic energy deposition from the high energy ions, except some cases where the synergy effect with the nuclear energy deposition plays an important role. In crystalline Si (c-Si), no tracks have been observed with any monomer ions up to GeV. Tracks are formed in c-Si under 40 MeV fullerene (C60) cluster ion irradiation, which provides much higher energy deposition than monomer ions. The track diameter decreases with decreasing the ion energy until they disappear at an extrapolated value of ~ 17 MeV. However, here we report the track formation of 10 nm in diameter under C60 ion irradiation of 6 MeV, i.e., much lower than the extrapolated threshold. The diameters of 10 nm were comparable to those under 40 MeV C60 irradiation. Furthermore, the tracks formed by 6 MeV C60 irradiation consisted of damaged crystalline, while those formed by 40 MeV C60 irradiation were amorphous. The track formation was observed down to 1 MeV and probably lower with decreasing the track diameters. The track lengths were much shorter than those expected from the drop of Se below the threshold. These track formations at such low energies cannot be explained by the conventional purely electronic energy deposition mechanism, indicating another origin, e.g., the synergy effect between the electronic and nuclear energy depositions, or dual transitions of transient melting and boiling. [ABSTRACT FROM AUTHOR]

Consider a constant mean curvature immersion F : U (⊂ R n) → M into an arbitrary Lorentzian (n + 1) -manifold M. A point o ∈ U is called a light-like point if the first fundamental form d s 2 of F degenerates at o. We denote by B F the determinant function of the symmetric matrix associated to d s 2 with respect to a local coordinate system at o. A light-like point o is said to be degenerate if the exterior derivative of B F vanishes at o. We show that if o is a degenerate light-like point, then the image of F contains a light-like geodesic segment of M passing through f(o) (cf. Theorem E). This explains why several known examples of constant mean curvature hypersurface in the Lorentz–Minkowski (n + 1) -space form R 1 n + 1 contain light-like lines on their sets of light-like points, under a suitable regularity condition of F. Several related results are also given. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. Methods: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. Results: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. Conclusion: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention. [ABSTRACT FROM AUTHOR]

We have already reported multi-photon excitation of tris(2,2′-bipyridyl)ruthenium complex [Ru(bpy)32+] by femtosecond pulse laser with near infrared wavelength as the light sources, the multi-photon sensitized polymerization of pyrrole and the 3D printing (photo-fabrication) system of polypyrrole (PPy) by 3D scanning of the laser focal point. In the present study, the 3D printing of PPy into a Nafion sheet was carried out to evaluate the electronic conductivity of the product micro-structures formed by multi-photon sensitized polymerization. When the PPy straight line structure was drawn in the direction of the optical axis (vertical), relatively higher conductivity values (Max 410 Scm−1) were obtained in the fully-doped state. The values of over 102 Scm−1 indicated the Drude model of electrical conduction, therefore, the micro-structures would be applied to a metamaterial. On the other hand, 1 or 2 orders of magnitude lower conductivity values were obtained from the crooked line structures drawn in the vertical and horizontal directions. This difference in the conductivity would be affected by the distorted cross section of the PPy deposition and the electrically overlapping of each deposition particle. [ABSTRACT FROM AUTHOR]

We investigate the relation between quadrics and their Christoffel duals on the one hand, and certain zero mean curvature surfaces and their Gauss maps on the other hand. To study the relation between timelike minimal surfaces and the Christoffel duals of 1-sheeted hyperboloids we introduce para-holomorphic elliptic functions. The curves of type change for real isothermic surfaces of mixed causal type turn out to be aligned with the real curvature line net. [ABSTRACT FROM AUTHOR]

Purpose: The diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) is able to diagnose DIC accurately and promptly. The aim of this retrospective study is to evaluate the degree of association between each parameter of JAAM DIC criteria and the diagnosis of trauma induced DIC (T-DIC) utilizing thromboelastometry (ROTEM). Methods: Trauma patients transported to our hospital with ROTEM performed in the emergency department between January 2013 and December 2015 were enrolled in this study. We evaluated (1) the characteristics of T-DIC, (2) the relationships between T-DIC and each parameter of the JAAM DIC criteria and (3) the diagnostic accuracies of each parameter for T-DIC by statistical measurement. Results: All 72 patients (21 T-DIC and 51 control) were included in primary analysis. T-DIC was significantly related to younger age, more severe trauma scores, more cases of massive transfusions, and remarkable coagulation abnormality detected by standard coagulation tests. In the cases of T-DIC, ROTEM showed longer clotting time, lower acceleration, lower clot firmness, and inhibited fibrinolysis in EXTEM/INTEM. Within the JAAM DIC score, PT-INR ≥1.2 was the most accurate factor for T-DIC diagnosis; sensitivity 60.0%, specificity 100.0%, and accuracy 88.7%. PT-INR ≥1.2 was statistically correlated with the JAAM DIC score ( p < 0.001, r = 0.709). The univariate analysis based on 1.2 of PT-INR indicated statistical differences in most categories of ROTEM, which is similar to analysis performed for the presence and absence of T-DIC. Conclusions: Among JAAM DIC criteria, the PT-INR ≥1.2 was the most accurate factor for both the diagnosis of T-DIC and the evaluation of its severity. [ABSTRACT FROM AUTHOR]

Gels have superior features such as high water content, permeability, extremely low friction, and biocompatibility, which are not found in the normal solids materials, because these features are due to their soft and wet properties. Now artificial gels approach the natural gels of the human body in property. In this study the frictional behavior of shape memory gel (SMG) was investigated. In addition to its shape-memory characteristic, SMG has low friction characteristics and better wear resistance than conventional gels. Its shape-memory characteristic is related to temperature. SMG is expected to be of practical use in medical and mechanical materials. This is because the SMG does not need chemical fixation, healing, placed around on object, and cools to conform to and grip the object, can expand it. This allows a decrease in solvent use and thus a decrease of patient burden in medical care, easier machine assembling and the design of machines with reduced part numbers, and the miniaturization of machines. In this study, implication water rate of SMGs of different composition is measured, and power by changing implication water rate reports the characteristic, and we performed the friction behavior of SMG for the purpose of the use to the underwater apparatus. [ABSTRACT FROM AUTHOR]

We discuss the Guichard duality for conformally flat hypersurfaces in a Euclidean ambient space. This duality gives rise to a Goursat-type transformation for conformally flat hypersurfaces, which is generically essential. Using a suitable representation of the associated family of a conformally flat hypersurface in Euclidean space, its dual as well as conformal images of their canonical principal Guichard net(s) are recovered from the family. It is shown that the hypersurface and its dual can be reconstructed from a Ribaucour pair of Guichard nets. [ABSTRACT FROM AUTHOR]

Background:Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor.Methods:A total of five pancreatic cancer murine models (two cell line-based xenografts (CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg−1, q3d × 4) alone or GEM plus iRGD peptide (8 μmol kg−1). Evaluation of NRP1 expression in xenografts and 48 clinical cancer specimens was performed by immunohistochemistry (IHC).Results:We identified a subset of pancreatic cancer models that showed NRP1 overexpression sensitive to iRGD co-administration. Treatment with GEM plus iRGD peptide resulted in a significant tumour reduction compared with GEM monotherapy in CXs, but not remarkable in TGs. Potential targets of iRGD were characterised as cases showing NRP1 overexpression (IHC-2+/3+), and these accounted for 45.8% of the clinical specimens.Conclusions:Internalised RGD peptide enhances the effects of co-administered drugs in pancreatic cancer models, its efficacy is however only appreciable in those employing cell lines. Therefore, the clinical application needs to be given careful consideration. [ABSTRACT FROM AUTHOR]

Objectives: Purpose: To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. Subjects and methods: Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. Results: Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfatocopherol were not significant following adjustments for smoking. Conclusion: Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects. [ABSTRACT FROM AUTHOR]

Purpose: Since 2006, we have been performing minimally invasive plate osteosynthesis with a palmar locking plate and without division of the pronator quadratus muscle for repairing distal radial fractures. The purpose of this study was to present the surgical technique we have developed and to retrospectively evaluate the clinical outcomes. Methods: Twenty patients were treated with this technique between January and December 2007. The range of motion of the wrist and forearm, grip strength, and the quick disability of the arm, shoulder, and hand score were assessed at the latest follow-up examination, and postoperative complications were evaluated. Results: The average ranges of flexion and extension of the wrist were 55° and 60°, respectively. The average ranges of supination and pronation of the forearm were 88° and 86°, respectively. The average grip strength of the treated side was 71 % of that of the uninjured side. The average quick disability of the arm, shoulder, and hand score was 13.4 points. No patient had loss of fracture reduction, implant failure, deep infection, or tendon or nerve problems. Conclusions: The small skin incisions of this technique are advantageous from the aesthetic viewpoint. Minimally invasive plate osteosynthesis is one of the options for the treatment of distal radial fractures. [ABSTRACT FROM AUTHOR]

Controlling the position of a magnetic domain wall with electric current may allow for new types of non-volatile memory and logic devices. To be practical, however, the threshold current density necessary for domain wall motion must be reduced below present values. Intrinsic pinning due to magnetic anisotropy, as recently observed in perpendicularly magnetized Co/Ni nanowires, has been shown to give rise to an intrinsic current threshold Jth0. Here, we show that domain wall motion can be induced at current densities 40% below Jth0 when an external magnetic field of the order of the domain wall pinning field is applied. We observe that the velocity of the domain wall motion is the vector sum of current- and field-induced velocities, and that the domain wall can be driven against the direction of a magnetic field as large as 2,000 Oe, even at currents below Jth0. We show that this counterintuitive phenomenon is triggered by Walker breakdown, and that the additive velocities provide a unique way of simultaneously determining the spin polarization of current and the Gilbert damping constant. [ABSTRACT FROM AUTHOR]

Purpose: BMS-690514 is a novel oral tyrosine kinase inhibitor of ErbB and vascular endothelial growth factor receptor. This open-label phase I dose-escalation study (ClinicalTrials.gov Identifier: NCT00516451) aimed to assess the safety, preliminary efficacy, pharmacokinetics, and pharmacodynamics of BMS-690514 in Japanese patients with advanced or metastatic solid tumors.Methods: Patients with advanced or metastatic solid tumors received oral BMS-690514 once daily continuously until disease progression or intolerable toxicity occurred. Dose-limiting toxicity (DLT) was evaluated from the first dose to Day 29. Dose levels at 100 and 200 mg were investigated. Assessments included adverse events, tumor response, pharmacokinetics, pharmacodynamics, 2 [18F] fluoro-2-deoxyglucose positron-emitting tomography, and epidermal growth factor receptor and K-ras mutations.Results: BMS-690514 at the dose of 100 mg (n = 3) or 200 mg (n = 3) was administered once daily to totally nine patients and was well tolerated up to 200 mg. No treatment-related serious adverse events or DLTs were reported. Frequently observed treatment-related AEs were acne, diarrhea, dry skin, hypertension, stomatitis, blood fibrinogen increased, hemoglobin decreased, pruritus, and hypoalbuminemia. These were generally reported as Grade 1 and 2. Five of 9 patients (56 %) had stable disease. Plasma concentrations of BMS-690514 reached Cmax within 3 h and declined with an effective half-life of approximately 10 and 12 h at 100 and 200 mg, respectively.Conclusions: Oral BMS-690514 was well tolerated in Japanese patients with advanced or metastatic solid tumors up to 200 mg. [ABSTRACT FROM AUTHOR]

The effect of the addition of propylene carbonate (PC) on the ion transport behaviour of nanocomposite polymer electrolytes having composition of polyethylene oxide-hexafluorophosphoric acid-fumed silica has been studied. The ionic conductivity of 6.89 × 10 S cm at 298 K has been obtained for these electrolytes along with good mechanical and thermal properties. The variation of H NMR linewidth with temperature shows line narrowing at the glass transition and melting temperature of the electrolytes which suggests the onset of long-range ion translational motion. The increase in ionic conductivity with the addition of PC is related to the transformation of these electrolytes to the amorphous phase which has been supported by X-ray diffraction results. The polymer electrolytes are thermally stable up to around 498 K and hence are suitable for various applications. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the features of chest computed tomography (CT) in children with swine-origin influenza A (H1N1) virus (S-OIV).Materials and Methods: The study population consisted of 16 children with laboratory-confirmed S-OIV infection (12 boys, 4 girls), with an age range of 5-10 years (mean 6.3 years). Pneumonia was suspected in these patients based on clinical features or confirmed by radiography. All subjects underwent CT for close evaluation of pneumonia, including characteristics, distribution, extent, and other findings such as pleural effusion, pneumothorax, and pneumomediastinum.Results: The predominant CT finding was consolidation plus ground-grass opacity (GGO) (11/16, 69%). The consolidation-dominant pattern was found in 10 of 16 (66%) patients, and 1 (6%) was GGO-dominant. One (6%) had only GGO. In all, 7 of the 16 patients had segmental or lobar consolidation. Abnormal opacities were primarily distributed in the central lung zone (8/16, 50%) and were multifocal (15/16, 94%). Four showed atelectasis (4/16, 25%). Pneumomediastinum was observed in 4 of 16 (25%). One patient had negative radiographic findings but was positive on CT.Conclusion: Multifocal consolidation with central distribution is a common CT finding in children with S-OIV, but there are few GGO-dominant cases. Widespread consolidation (segmental or lobar) is also common. [ABSTRACT FROM AUTHOR]

Purpose: LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Methods: Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. Results: LY2181308 was administered to 14 patients, aged 44-73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. Conclusions: LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy. [ABSTRACT FROM AUTHOR]

Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m2) and CY (120 mg/kg) or melphalan (210 mg/m2), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼180 mg/m2) and melphalan (140 mg/m2) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5±15.0% for MAST group and 85.0±8.0% for RIST group, and the 3-year OS rate was 54.5±15.0% for MAST group and 95.0±4.9% for RIST group (P=0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV. [ABSTRACT FROM AUTHOR]

Background: Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC).Methods: Patients with unresectable stage IIIA or IIIB NSCLC were treated with nedaplatin (NP) at 50 mg m(-2) and irinotecan (CPT) at 60 mg m(-2) on days 1 and 8 every 4 weeks for two to four cycles with concurrent TRT (2 Gy per day, total 60 Gy).Results: All 35 patients were able to receive a total of 60 Gy. Adverse effects and events in chemotherapy with TRT were grade 3 or 4 anaemia, neutropenia and thrombocytopenia, which occurred in 3.0%, 32.8% and 6.0% of patients, respectively. There was no grade 3 pneumonitis or oesophagitis. Adverse effects and events in chemotherapy alone were mild. There was no treatment-related death. An overall response rate was 94.3%. The median progression-free and overall survivals were 13.0 and 36.0 months, respectively. The 5-year disease-free and overall survival rates were 25.7% and 40.0%, respectively.Conclusion: NP and CPT treatment with concurrent TRT is effective and safe for patients with unresectable, locally advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis reflects the presence of hypoxia, which can be indicative of an aggressive tumour phenotype. The aim of this study was to investigate whether histological necrosis is a useful predictor of outcome in patients with pancreatic ductal carcinoma (PDC).Methods: We reviewed histopathological findings in 348 cases of PDC in comparison with clinicopathological information. We counted small necrotic foci (micronecrosis) as necrosis, in addition to massive necrosis that had been only defined as necrosis in previous studies. The reproducibility of identifying histological parameters was tested by asking five independent observers to blindly review 51 examples of PDC.Results: Both micronecrosis and massive necrosis corresponded to hypoxic foci expressing carbonic anhydrase IX detected by immunohistochemistry. Multivariate survival analysis showed that histological necrosis was an independent predictor of poor outcome in terms of both disease-free survival (DFS) and disease-specific survival (DSS) of PDC patients. In addition, metastatic status, and lymphatic, venous, and intrapancreatic neural invasion were independent prognostic factors for shorter DFS and metastatic status, margin status, lymphatic invasion, and intrapancreatic neural invasion were independent prognostic factors for DSS. The interobserver reproducibility of necrosis identification among the five independent observers was 'almost perfect' (κ-value of 0.87).Conclusion: Histological necrosis is a simple, accurate, and reproducible predictor of postoperative outcome in PDC patients. [ABSTRACT FROM AUTHOR]

Background: Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion.Methods: In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay.Results: Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients.Conclusion: These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM. [ABSTRACT FROM AUTHOR]

Disrupted-in-schizophrenia 1 (DISC1) is a promising susceptibility gene for major mental illness. Recent studies have implicated DISC1 in key neurodevelopmental processes, including neurite outgrowth, neuronal migration and proliferation. Here, we report that DISC1 regulates cell–cell and cell–matrix adhesion and neurite outgrowth. DISC1 overexpression increased expression of the adherence junction protein N-cadherin and enhanced cell–cell adhesion. The increased N-cadherin accumulated in the areas of cell–cell contact. DISC1 overexpression also enhanced cell–matrix adhesion by inducing expression of β1-integrin protein. In the presence of nerve growth factor (NGF), DISC1 overexpression increased β1-integrin expression at the cell membrane and growth cone. NGF-induced neurite extension was enhanced by DISC1, and anti-β1-integrin antibody reduced the neurite outgrowth of DISC1-overexpressing cells to the control level. Furthermore, DISC1 also regulated N-cadherin and β1-integrin expression at the cell membrane in primary neurons. We conclude that DISC1 regulates cell–cell adhesion and cell–matrix adhesion by regulating the expression of adhesion molecules. [ABSTRACT FROM AUTHOR]

A Mott insulator is a material that is insulating because of strong Coulomb repulsions between electrons. Doping charge carriers, electrons or holes into a Mott insulator can induce high-temperature superconductivity. Thus, what exactly happens when a charge carrier is doped into a Mott insulator is a key question in many-body physics. To address this issue, ideally one should start from a zero-doping state and be able to introduce both holes and electrons in the dilute limit. However, such an idealized experiment has been impossible because of the lack of suitable materials. Here we show that a new ‘ambipolar’ cuprate makes it possible for the first time to cross the zero-doping state in the same material, which in turn allows us to address the physics of the extremely low-doping region. Surprisingly, we found that the antiferromagnetic ground state sharply changes between electron- and hole-doped sides, and this change is dictated by the existence of only 0.1 ppm of charge carriers. Moreover, we observed that the Néel temperature TN shows an unexpected reduction in a narrow range centred at the zero-doping state, across which the system exhibits asymmetric behaviours in transport measurements. Our findings reveal the inherently different nature of electron and hole doping in the dilute limit of a Mott-insulating cuprate. [ABSTRACT FROM AUTHOR]

Diabetogenic loci for type 2 diabetes have been mapped to mouse chromosome (Chr) 11 and 14 in the Nagoya–Shibata–Yasuda (NSY) mouse, an animal model of type 2 diabetes. We aimed to obtain direct evidence of these genes on each chromosome and to clarify their function and interaction in conferring susceptibility to type 2 diabetes. We established three consomic strains homozygous for diabetogenic NSY-Chr11, NSY-Chr14 or both on the control C3H background (C3H-11NSY, C3H-14NSY and C3H-11NSY14NSY, respectively), and monitored diabetes-related phenotypes longitudinally. The glucokinase gene was sequenced as a positional candidate gene on Chr11. C3H-11NSY mice showed hyperglycaemia associated with impaired insulin secretion and age-dependent insulin resistance without obesity. C3H-14NSY mice exhibited hyperglycaemia mainly due to insulin resistance, with a slight increase in percentage body fat. C3H-11NSY14NSY double consomic mice showed marked hyperglycaemia and obesity, which was not observed in single consomic strains. Sequences of the glucokinase gene were allelically variant between NSY and C3H mice. These data provide direct evidence that Chr11 and Chr14 harbour major susceptibility genes for type 2 diabetes. These two chromosomes interact to cause more severe hyperglycaemia and obesity, which was not observed with the presence of either single chromosome, indicating different modes of gene–gene interaction depending on the phenotype. Marked changes in the phenotypes retained in the consomic strains will facilitate fine mapping and the identification of the responsible genes and their interaction with each other, other genes and environmental factors. [ABSTRACT FROM AUTHOR]