Hydrogen Bonding Propagated Phase Separation in Quasi-Epitaxial Single Crystals: A Pd-Br Molecular Insulator.

In condensed matter, phase separation is strongly related to ferroelasticity, ferroelectricity, ferromagnetism, electron correlation, and crystallography. These ferroics are important for nano-electronic devices such as non-volatile memory. However, the quantitative information regarding the lattice (atomic) structure at the border of phase separation is unclear in many cases. Thus, to design electronic devices at the molecular level, a quantitative electron-lattice relationship must be established. Herein, we elucidated a PdII-PdIV/PdIII-PdIII phase transition and phase separation mechanism for [Pd(cptn)2Br]Br2 (cptn = 1R,2R-diaminocyclopentane), propagated through a hydrogen-bonding network. Although the Pd···Pd distance was used to determine the electronic state, the differences in the Pd···Pd distance and the optical gap between Mott-Hubbard (MH) and charge-density-wave (CDW) states were only 0.012 Å and 0.17 eV, respectively. The N-H···Br···H-N hydrogen-bonding network functioned as a jack, adjusting the structural difference dynamically, and allowing visible ferroelastic phase transition/separation in a fluctuating N2 gas flow. Additionally, the effect of the phase separation on the spin susceptibility and electrical conductivity were clarified to represent the quasi-epitaxial crystals among CDW-MH states. These results indicate that the phase transitions and separations could be controlled via atomic and molecular level modifications, such as the addition of hydrogen bonding.

Subcycle mid-infrared coherent transients at 4 MHz repetition rate applicable to light-wave-driven scanning tunneling microscopy.

We produce subcycle mid-infrared (MIR) pulses at a 4 MHz repetition rate via the optical rectification (OR) of sub-10 fs near-infrared pulses delivered by an optical parametric chirped pulse amplifier. The coherent MIR pulses generated in a GaSe crystal under an ultrabroadband phase-matching condition contain only 0.58-0.85 oscillation cycles within the full width at half-maximum of the intensity envelope. The use of OR enables excellent phase stability of 56 mrad over 5.6 h, which is confirmed by field-resolved detection using electro-optic sampling. An electromagnetic simulation using a finite integration technique reveals that the peak field strength can easily exceed 10 V/nm owing to the field enhancement resulting from focusing MIR pulses onto a tunnel junction.

Surface-mediated spin dynamics probed by optical-pump-probe scanning tunneling microscopy.

In current materials science and technologies, surface effects on carrier and spin dynamics in functional materials and devices are of great importance. In this paper, we present the surface-sensitive probing of electron spin dynamics, performed by optical-pump-probe scanning tunneling microscopy (OPP-STM). Time-resolved spin lifetime information on a manganese (Mn)-deposited GaAs(110) surface was successfully obtained for the first time. With increasing Mn density via in situ evaporation, a nonlinear change in the spin lifetime in the picosecond range was clearly observed, while directly confirming the Mn density by STM. In comparison with the results obtained by the conventional OPP method, we have also demonstrated that the observed nonlinear spin lifetime behavior was surface-mediated, which can be characterized using only the surface-sensitive OPP-STM technique.

Dynamic probe of ZnTe(110) surface by scanning tunneling microscopy.

The reconstructed surface structure of the II-VI semiconductor ZnTe (110), which is a promising material in the research field of semiconductor spintronics, was studied by scanning tunneling microscopy/spectroscopy (STM/STS). First, the surface states formed by reconstruction by the charge transfer of dangling bond electrons from cationic Zn to anionic Te atoms, which are similar to those of IV and III-V semiconductors, were confirmed in real space. Secondly, oscillation in tunneling current between binary states, which is considered to reflect a conformational change in the topmost Zn-Te structure between the reconstructed and bulk-like ideal structures, was directly observed by STM. Third, using the technique of charge injection, a surface atomic structure was successfully fabricated, suggesting the possibility of atomic-scale manipulation of this widely applicable surface of ZnTe.

Externally-triggerable optical pump-probe scanning tunneling microscopy with a time resoloution of tens-picosecond.

Photoinduced carrier dynamics of nanostructures play a crucial role in developing novel functionalities in advanced materials. Optical pump-probe scanning tunneling microscopy (OPP-STM) represents distinctive capabilities of real-space imaging of such carrier dynamics with nanoscale spatial resolution. However, combining the advanced technology of ultrafast pulsed lasers with STM for stable time-resolved measurements has remained challenging. The recent OPP-STM system, whose laser-pulse timing is electrically controlled by external triggers, has significantly simplified this combination but limited its application due to nanosecond temporal resolution. Here we report an externally-triggerable OPP-STM system with a temporal resolution in the tens-picosecond range. We also realize the stable laser illumination of the tip-sample junction by placing a position-movable aspheric lens driven by piezo actuators directly on the STM stage and by employing an optical beam stabilization system. We demonstrate the OPP-STM measurements on GaAs(110) surfaces, observing carrier dynamics with a decay time of [Formula: see text] ps and revealing local carrier dynamics at features including a step edge and a nanoscale defect. The stable OPP-STM measurements with the tens-picosecond resolution by the electrical control of laser pulses highlight the potential capabilities of this system for investigating nanoscale carrier dynamics of a wide range of functional materials.

Physical performance and knee osteoarthritis among community-dwelling women in Japan: the Hizen-Oshima Study, cross-sectional study.

Osteoarthritis (OA) is the most common chronic joint disorder. Relationships between knee OA and physical performance have been examined, but mainly in patients with knee OA. Clarifying the relationship between knee OA and physical performance among community-dwelling individuals is thus important. Subjects comprised 563 community-dwelling Japanese women. Radiographic knee OA was defined as Kellgren-Lawrence criteria grade 2 or higher. Painful knee OA was defined as radiographic OA combined with knee pain. We evaluated performance-based measures of physical functioning. Student's t tests were used to compare continuous variables. Adjusted means of performance-based measures were compared between groups using general linear modeling methods. Mean age was 64.3 years. Women with radiographic OA were older than those without OA (P < 0.0001). BMI was greater in women with radiographic OA than in women without OA (P < 0.0001). In univariate analysis, women with radiographic OA displayed worse physical functioning than women without OA, with longer chair stand time, longer walking time, and shorter functional reach. Performance-based measurements with painful OA resembled those with radiographic OA. Age- and BMI-adjusted means of chair stand time and walking time were longer in women with radiographic or painful knee OA than in women without OA (P < 0.0001 each). Furthermore, chair stand and walking took longer for women with painful knee OA than for women with radiographic knee OA. Women with knee OA showed deteriorated performance of chair stand and walking. Painful knee OA was associated with poorer performance than radiographic knee OA.

Versatile Post-Doping toward Two-Dimensional Semiconductors.

We have developed a simple and straightforward way to realize controlled postdoping toward 2D transition metal dichalcogenides (TMDs). The key idea is to use low-kinetic-energy dopant beams and a high-flux chalcogen beam simultaneously, leading to substitutional doping with controlled dopant densities. Atomic-resolution transmission electron microscopy has revealed that dopant atoms injected toward TMDs are incorporated substitutionally into the hexagonal framework of TMDs. The electronic properties of doped TMDs (Nb-doped WSe2) have shown drastic change and p-type action with more than 2 orders of magnitude increase in current. Position-selective doping has also been demonstrated by the postdoping toward TMDs with a patterned mask on the surface. The postdoping method developed in this work can be a versatile tool for 2D-based next-generation electronics in the future.

Cross-sectional and longitudinal studies of three-dimensional stereotactic surface projection SPECT analysis in Parkinson's disease.

Although dementia is increasingly recognized as a common feature in Parkinson's disease (PD), its pathological substrate remains unknown. We conducted cross-sectional and longitudinal brain perfusion SPECT analyses to explore changes during the course of developing dementia in PD. Fifty-five patients originally diagnosed with PD were imaged in the cross-sectional study. Twenty-one of these, nine without dementia and 12 with dementia (PDD), were included in the longitudinal study to observe perfusion changes during the course of their disease. Data were analyzed using three-dimensional stereotactic surface projection SPECT analysis. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose PD and the revised criteria for the clinical diagnosis of dementia with Lewy bodies for PDD. The cross-sectional study showed that patients with PDD had significantly reduced perfusion in the right posterior cingulate, the right precuneus and the left posterior cingulate area. In the longitudinal study, significantly reduced perfusion was observed in the left anterior frontal gyrus in PD without dementia, and in the right inferior parietal lobule in those that developed PDD. We suggest that a relationship exists between developing dementia in PDD and reduced perfusion in the posterior parietal area.

Evolution of local conductance pathways in a single-molecule junction studied using the three-dimensional dynamic probe method.

Understanding of the dynamics of the bonding states of molecules with electrodes while the molecular conformation is changed is particularly important for elucidating the details of electrochemical devices as well as molecular devices in which the reaction dynamics of the electrodes and molecules plays an important role, such as in fuel cells, catalysis and bioelectrochemical devices. However, it has been difficult to make measurements when the distance between counter electrodes is short, namely, the molecule is raised from a lying form, almost parallel and close to the electrodes, toward a standing form and vice versa. We previously have developed a method called the three-dimensional (3D) dynamic probe method, which enables conductance measurement while the conformation of a single-molecule junction is precisely controlled by scanning tunneling microscopy (STM) techniques. Here, by combining this method with density functional theory (DFT) calculations, it has become possible to simultaneously consider the effects of the dynamics of molecular structures and the bonding states at the electrodes on the local transmission pathways, local-bond contributions to conductance. Here, by performing an analysis on 1,4-benzenediamine (BDA) and 1,4-benzenedithiol (BDT) single molecule junctions, we have observed, for the first time, the effect of a change in the molecular conformations and bonding states on the local transmission pathways for a short Au electrode distance condition.

Continuous Heteroepitaxy of Two-Dimensional Heterostructures Based on Layered Chalcogenides.

The in-plane connection and layer-by-layer stacking of atomically thin layered materials are expected to allow the fabrication of two-dimensional (2D) heterostructures with exotic physical properties and future engineering applications. However, it is currently necessary to develop a continuous growth process that allows the assembly of a wide variety of atomic layers without interface degradation, contamination, and/or alloying. Herein, we report the continuous heteroepitaxial growth of 2D multiheterostructures and nanoribbons based on layered transition metal dichalcogenide (TMDC) monolayers, employing metal organic liquid precursors with high supply controllability. This versatile process can avoid air exposure during growth process and enables the formation of in-plane heterostructures with ultraclean atomically sharp and zigzag-edge straight junctions without defects or alloy formation around the interface. For the samples grown directly on graphite, we have investigated the local electronic density of states of atomically sharp heterointerface by scanning tunneling microscopy and spectroscopy, together with first-principles calculations. These results demonstrate an approach to realizing diverse nanostructures such as atomic layer-based quantum wires and superlattices and suggest advanced applications in the fields of electronics and optoelectronics.

The effect of nitrogen lone-pair interaction on the conduction in a single-molecule junction with amine-Au bonding.

We have applied our previously developed three-dimensional dynamic probe method to analyze the conductance in a Au-/1,4-benzenediamine (BDA)/Au single molecule junction. This structure is a typically used example to demonstrate the high performance of the break junction (BJ) method for measuring conductance with small variations, however, details of the interaction of the nitrogen (N) lone-pair in the amine group with a Au electrode, which is considered to have a fundamental role in determining the conductance of the single molecule junction with the amine, have not yet been clarified and still remain an important issue to be resolved. In this study, we have succeeded, for the first time, in observing the site-dependent change in conductance of this system while the molecular conformation was accurately controlled, and the results were well reproduced by a simulation taking account of the effect of the N lone-pair in an amine bonding with a Au electrode.

Umbilical metastasis from breast cancer related with tumor marker elevation.

We describe a 53-year-old woman with tumor marker abnormality caused by an umbilical metastasis from breast cancer. She had undergone breast conservation therapy (BCT) for breast cancer (T2N1M0) 9 years previously. Umbilical metastasis was detected 9 months after tumor marker elevation was first noted. After resection of the umbilical metastasis, tumor marker level decreased immediately and normalized. The patient is alive without other metastasis.

Revealing the Conformational Dynamics in a Single-Molecule Junction by Site- and Angle-Resolved Dynamic Probe Method.

Single-molecule junctions have been extensively studied because of their high potential for future nanoscale device applications as well as their importance in basic studies for molecular science and technology. However, since the bonding sites at an electrode and the molecular tilt angles, for example, cannot be determined experimentally, analyses have been performed assuming the structures of such interactive key factors, with uncertainties and inconsistencies remaining in the proposed mechanisms. We have developed a methodology that enables the probing of conformational dynamics in single-molecule junctions simultaneously with the direct characterization of molecular bonding sites and tilt angles. This technique has revealed the elemental processes in single-molecule junctions, which have not been clarified using conventional methods. The mechanisms of the molecular dynamics in 1,4-benzenedithiol and 4,4'-bipyridine single-molecule junctions, which, for example, produce binary conductance switching of different types, were clearly discriminated and comprehensively explained.

Attractive interaction between Mn atoms on the GaAs(110) surface observed by scanning tunneling microscopy.

Scanning tunneling microscopy/spectroscopy (STM/STS) was carried out to investigate the structures of Mn atoms deposited on a GaAs(110) surface at room temperature to directly observe the characteristics of interactions between Mn atoms in GaAs. Mn atoms were paired with a probability higher than the random distribution, indicating an attractive interaction between them. In fact, re-pairing of unpaired Mn atoms was observed during STS measurement. The pair initially had a new structure, which was transformed during STS measurement into one of those formed by atom manipulation at 4 K. Mn atoms in pairs and trimers were aligned in the <110> direction, which is theoretically predicted to produce a high Curie temperature.

Modulation of electrical potential and conductivity in an atomic-layer semiconductor heterojunction.

Semiconductor heterojunction interfaces have been an important topic, both in modern solid state physics and in electronics and optoelectronics applications. Recently, the heterojunctions of atomically-thin transition metal dichalcogenides (TMDCs) are expected to realize one-dimensional (1D) electronic systems at their heterointerfaces due to their tunable electronic properties. Herein, we report unique conductivity enhancement and electrical potential modulation of heterojunction interfaces based on TMDC bilayers consisted of MoS2 and WS2. Scanning tunneling microscopy/spectroscopy analyses showed the formation of 1D confining potential (potential barrier) in the valence (conduction) band, as well as bandgap narrowing around the heterointerface. The modulation of electronic properties were also probed as the increase of current in conducting atomic force microscopy. Notably, the observed band bending can be explained by the presence of 1D fixed charges around the heterointerface. The present findings indicate that the atomic layer heterojunctions provide a novel approach to realizing tunable 1D electrical potential for embedded quantum wires and ultrashort barriers of electrical transport.

CYP17 polymorphism as a risk factor of tamoxifen-induced hepatic steatosis in breast cancer patients.

Oral administration of tamoxifen, an endocrine therapy for breast cancer, often induces hepatic steatosis (THS, tamoxifen-induced hepatic steatosis) as a complication, which can progress to non-alcoholic steatohepatitis (NASH). The development of this complication is strongly associated with three clinical risk factors; specifically, insulin resistance, central obesity, and hypertriglyceridemia, however a genetic predisposition to THS has yet to be investigated. The aim of this study is to determine whether genetic polymorphism of the P450c17alpha enzyme coded for by the CYP17 gene, responsible for regulating serum estrogen, has an association with THS. After obtaining informed consent from 180 eligible breast cancer patients treated with tamoxifen, DNA was collected and analyzed by restriction fragment length polymorphism assay and classified into alleles defined as A1 and A2. The absence or presence and extent of THS was evaluated by calculating the liver/spleen (L/S) ratio based on Hounsfield units with a CT scanner. Administration of tamoxifen led to THS (L/S ratio <0.9) in 57 (31.7%) of 180 patients while the remaining 123 (68.3%) patients did not develop THS. A significant difference in the distribution of CYP17 genotypes was observed between patients who developed THS and those who did not (P=0.021). A significantly higher frequency of the A2 allele was seen in the THS group (odds ratio, 1.90; 95% confidence interval, 1.21-2.99). Our study provides the first evidence that CYP17 polymorphism participates in the development of THS, and sheds light on the genetic causes of this side effect and genetic differences between tamoxifen-treated individuals.

Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide.

The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis.

CYP17 polymorphism and tamoxifen-induced hepatic steatosis.

Hepatic steatosis is a frequent complication, which sometimes develops nonalcoholic steatohepatitis (NASH), in breast cancer patients treated with tamoxifen, a potent antagonist of estrogen. Recently we reported the impairment of fatty acid beta-oxidation and the enhancing fatty infiltration to hepatocytes in aromatase deficiency (ArKO) mice as the estrogen deficiency models. This experimental observation let us speculate strong link between estrogen and hepatic steatosis. In this study, we investigated whether a polymorphism in the cytochrome P450c17alpha gene (CYP17), which is associated with circulating estrogen levels, influences the development of tamoxifen-induced hepatic steatosis. This consecutive study included 180 breast cancer patients undergoing tamoxifen treatment. Genomic DNA extracted from the peripheral blood of each patient was analyzed by restriction fragment length polymorphism (defined as the A1 and A2 alleles). The extent of hepatic steatosis was assessed by computed tomography (CT) as the liver/spleen (L/S) ratio. While receiving adjuvant tamoxifen, 57 of 180 patients developed hepatic steatosis (L/S ratio <0.9) without obvious changes in body mass index (BMI). We observed a significant association between the A2/A2 genotype and the development of hepatic steatosis compared with the A1/A1 genotype [odds ratio (OR), 3.60; 95% confidence interval (C.I.)=1.42-9.10]. The A1/A2 genotype was at an intermediately increased risk of hepatic steatosis (OR, 2.24; 95% C.I.=0.99-5.08). The presence of the A2 allele possibly increased the progression of hepatic steatosis with a gene dosage effect (P=0.06). Our results suggest that functional polymorphism in CYP17 may be involved in determining susceptibility of tamoxifen-induced hepatic steatosis.

In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic steatohepatitis using semiquantative (123)I-BMIPP liver scan.

Recent progress of studies in NASH displays multi-disciplinary characters of the pathogeneses. Despite these advances, the strategic use of imaging modalities such as CT, US, and MRI, remains a relatively low priority in clinical situations, because these can only visualize the presence of fatty infiltration to the hepatic parenchyma, impossible to figure out the dynamic function of NASH liver. Morphological alteration such as CT value, MR signal intensity and echo-grade do not distinguish NASH from simple fatty liver. In this presentation, from a radiologic viewpoint, we show the feasibility of in vivo fatty acid imaging with (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP). BMIPP is an (123)I labeled fatty acid analog for imaging damaged myocardium, using conventional nuclear imaging equipment. Under normal conditions, the energy source for myocardial utilization is dependent on the beta-oxidation of fatty acids. For energy production in ischemic myocardium, the drastic switch from reduced beta-oxidation of fatty acids to glucose metabolism is well known. BMIPP can detect the area of reduced fatty acids metabolism on myocardial imaging and the data can be converted into semiquantitative analysis. Therefore, we speculate that the use of BMIPP to in vivo hepatic imaging in NASH could highlight a lot of matters of NASH. Details of this presentation include: (1) Hepatic imaging with BMIPP; (2) Clearance of BMIPP from NASH liver; (3) semiquantitative analysis of hepatic BMIPP clearance and clinical features of NASH; (4) Profiles of NASH categorized by BMIPP imaging and (5) Preliminary data of BMIPP clearance in patients with Tamoxifen-induced NASH. The core of our stance in this presentation is searching for valuable advice on clinical use of BMIPP in patients with NASH from specialists in the field of HEPATOLOGY.

Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients.

PURPOSE: The purpose of this study was to evaluate the predictive value of six different biological factors for neoadjuvant chemotherapy (NAC) in breast conservation treatment (BCT) for invasive breast cancer. MATERIALS AND METHODS: Thirty invasive breast cancer patients (31 breasts) who received NAC as BCT and needle biopsy before chemotherapy were included in this study. Breast cancer tissue was obtained with an 18G core needle with ultrasound guidance. Patients received two to five courses of CAF (cyclophosphamide 600 mg/m(2), pirarubicin 20-40 mg, 5-fluorouracil 600 mg/m(2)). Tissue sections from formalin-fixed paraffin-embedded blocks were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER (human epidermal growth factor receptor)-2, p53 protein, Bcl-2, and MIB-1 (Ki-67). Tumor reduction rate was assessed by MRI before and after chemotherapy. RESULTS: The tumor reduction rate did not differ according to the number of courses of chemotherapy administered. In both the univariate and multivariate analyses, HER-2-negative status was the only significant predictive factor of response (P<0.05). There was no correlation between response and hormone receptors, MIB-1, p53 protein, or Bcl-2 expression. CONCLUSION: This study suggests that breast cancer cells that overexpress HER-2 may be resistant to low-doses of anthracycline-based chemotherapy.