Critical behavior of nonequilibrium depinning transitions for vortices driven by current and vortex density.

We study the critical dynamics of vortices associated with dynamic disordering near the depinning transitions driven by dc force (dc current I) and vortex density (magnetic field B). Independent of the driving parameters, I and B, we observe the critical behavior of the depinning transitions, not only on the moving side, but also on the pinned side of the transition, which is the first convincing verification of the theoretical prediction. Relaxation times, [Formula: see text] and [Formula: see text], to reach either the moving or pinned state, plotted against I and B, respectively, exhibit a power-law divergence at the depinning thresholds. The critical exponents of both transitions are, within errors, identical to each other, which are in agreement with the values expected for an absorbing phase transition in the two-dimensional directed-percolation universality class. With an increase in B under constant I, the depinning transition at low B is replaced by the repinning transition at high B in the peak-effect regime. We find a trend that the critical exponents in the peak-effect regime are slightly smaller than those in the low-B regime and the theoretical one, which is attributed to the slight difference in the depinning mechanism in the peak-effect regime.

Tolerance to Stretching in Thiol-Terminated Single-Molecule Junctions Characterized by Surface-Enhanced Raman Scattering.

We investigated the change in the metal-molecule interaction in a 1,4-benzenedithiol (BDT) single-molecule junction using a combination of surface-enhanced Raman scattering spectra and current-voltage curves. During the stretching process, the conductance of the junction systematically decreased, accompanied by an increase in the vibrational energy of the CC stretching mode. By analyzing the current-voltage curves and Raman spectra, we found that the interaction between the π orbital of BDT and the electronic states of Au was diminished by the orientation change of BDT during the stretching process. A comparison with a 4,4'-bipyridine single-molecule junction revealed that the reduction of coupling of the Au-S contacts was smaller than that of Au-pyridine contacts. Therefore, the electronic states originating from the contact geometry are responsible for the tolerance to the stretching of thiol-terminated molecular junctions.

A dose-finding approach for genomic patterns in phase I trials.

Precision medicine is an emerging approach for disease treatment and prevention that accounts for individual variability in genes, environment, and lifestyle. Cancer is a genomic disease; therefore, the dose-efficacy and dose-toxicity relationships for molecularly targeted agents in cancer most likely differ, based on the genomic mutation pattern. The individualized optimal dose - the maximal efficacious dose with a clinically acceptable safety profile - may vary depending on the genomic mutation patterns and should be determined prior to the use of these agents in precision medicine. In addition, genes that influence the individualized optimal doses should be identified in early-phase development. In this study, we propose a novel dose-finding approach to identify the individualized optimal dose for molecularly targeted agents in phase I cancer trials. Individualized optimal dose determination and gene selection were conducted simultaneously based on L1 and L2 penalized regression. Similar to most reported dose-finding approaches, this study considers non-monotonic patterns for dose-efficacy and dose-toxicity relationships, as well as correlations between efficacy and toxicity outcomes based on multinomial distribution. Our dose-finding algorithm is based on the predictive probability calculated with an estimated penalized regression model. We compare the operating characteristics between the proposed and existing methods by simulation studies under various scenarios.

Quantum Criticality inside the Anomalous Metallic State of a Disordered Superconducting Thin Film.

The field-induced superconductor-insulator transition (SIT) in two-dimensional (2D) systems is a famous example of a quantum phase transition. However, an emergence of an anomalous metallic state induced by field has been a long-standing problem in 2D superconductors. While theories predicted that the emergence is attributed to strong phase fluctuations of the superconducting order parameter due to quantum fluctuations, usual resistance measurements have not probed them directly. Here, using Nernst effect measurements, we uncover superconducting fluctuations in the vicinity of the field-induced metallic state in an amorphous Mo_{x}Ge_{1-x} thin film. The field range where the vortex Nernst signals are detectable remains nonzero toward zero temperature, and it locates inside the metallic state defined by the magnetoresistance, indicating that the metallic state results from quantum vortex liquid (QVL) with phase fluctuations due to quantum fluctuations. Slow decay of transport entropy of vortices in the QVL with decreasing temperature suggests that the metallic state originates from broadening of a quantum critical point in SIT.

Critical behavior near the reversible-irreversible transition in periodically driven vortices under random local shear.

When many-particle (vortex) assemblies with disordered distribution are subjected to a periodic shear with a small amplitude [Formula: see text], the particles gradually self-organize to avoid next collisions and transform into an organized configuration. We can detect it from the time-dependent voltage [Formula: see text] (average velocity) that increases towards a steady-state value. For small [Formula: see text], the particles settle into a reversible state where all the particles return to their initial position after each shear cycle, while they reach an irreversible state for [Formula: see text] above a threshold [Formula: see text]. Here, we investigate the general phenomenon of a reversible-irreversible transition (RIT) using periodically driven vortices in a strip-shaped amorphous film with random pinning that causes local shear, as a function of [Formula: see text]. By measuring [Formula: see text], we observe a critical behavior of RIT, not only on the irreversible side, but also on the reversible side of the transition, which is the first under random local shear. The relaxation time [Formula: see text] to reach either the reversible or irreversible state shows a power-law divergence at [Formula: see text]. The critical exponent is determined with higher accuracy and is, within errors, in agreement with the value expected for an absorbing phase transition in the two-dimensional directed-percolation universality class. As [Formula: see text] is decreased down to the intervortex spacing in the reversible regime, [Formula: see text] deviates downward from the power-law relation, reflecting the suppression of intervortex collisions. We also suggest the possibility of a narrow smectic-flow regime, which is predicted to intervene between fully reversible and irreversible flow.

Investigation of Ag and Cu Filament Formation Inside the Metal Sulfide Layer of an Atomic Switch Based on Point-Contact Spectroscopy.

The atomic switches have attracted wide attention owing to their applications in nonvolatile electric devices. The atomic switch is operated by the formation and dissipation of a metallic filament inside a metal sulfide film, which is controlled by a solid electrochemical reaction. Although the metallic filament is considered to consist of metal atoms, the chemical species of the metallic filament are difficult to be identified due to challenges in observing the metallic filament inside the solid. In this study, we report the investigation on the metallic filament in the atomic switch with metal sulfide based on point-contact spectroscopy (PCS). By cooling the atomic switch, the switch voltage increased to 1 V, which allowed for the PCS measurement. The PCS revealed that the metallic filament was composed of Ag atoms in the case of the Pt/Ag2S/Ag atomic switch. We applied this technique to the Pt/Cu2S/Ag and Pt/Ag2S/Cu atomic switches to uncover the formation process of the metallic filament. In both atomic switches, the chemical species of the metallic filament were Ag. The metal atoms were supplied from both the metal electrode and the sulfide layer.

Relationship between dietary patterns and stunting in preschool children: a cohort analysis from Kwale, Kenya.

OBJECTIVES: Stunting is a significant cause of poor cognitive performance and lower school achievement. Stunting is observed among pre-school children in several areas in Africa; however, not all children are affected, and children with and without stunting are seen in the same communities. Therefore, this study aimed to identify nutritional and other factors that prevent stunting that may exist in local communities. STUDY DESIGN: This is a prospective cohort study. METHODS: Data were extracted from the Health and Demographic Surveillance System conducted in Kwale County, Kenya. The cohort consisted of all households with children less than five years old, within a radius of 2.2 km from a local health centre. A dietary pattern (DP) survey with a semi-quantitative food frequency questionnaire was conducted on caretakers of children who were voluntary participated from the cohort between June 2012 and August 2012. Using cluster analysis, the children were assigned to a DP group. Logistic regression analysis was applied to calculate the adjusted odds ratios (aORs) of DPs for stunting controlling for other factors. RESULTS: In total, 402 children were included in the analysis. By cluster analysis, three DPs were identified: protein-rich DP; traditional DP; and traditional DP complemented by breastfeeding. The aOR of a child becoming stunted from a normal height during the study period among children who received a traditional DP compared with those who had a protein-rich DP was 2.78 (95% confidence interval [CI]: 1.02-7.55). However, the aOR for children who were already stunted at the start of the study and had a traditional DP was 1.49 (95% CI: 0.82-2.72). Increased aORs of stunting were observed among children aged over 12 months compared with children aged 6-11 months, and the effects of DPs were modified by age in months from 12 to 35 months; however, the effects were near the null value for children over 36 months of age, although these were not statistically significant. CONCLUSIONS: We found that the traditional DP showed a higher risk for stunting compared with the protein-rich DP, and the most vulnerable age range for stunting was between 12 and 35 months. Interventions to prevent stunting should focus on providing 12- to 35-month-old children with locally available, protein-rich foods.

Stretch dependent electronic structure and vibrational energy of the bipyridine single molecule junction.

We have studied the stretch dependence of the electronic structure and vibrational energy for the 4,4'-bipyridine (BPY) single molecule junction, which was fabricated by the mechanically controllable break junction (MCBJ) using the highly stable nano MCBJ electrodes. The electronic structure and vibrational energy of the single molecule junction were studied by the current-voltage (I-V) curve and surface enhanced Raman scattering (SERS), respectively. The simultaneous SERS and I-V curve measurements revealed the lowest unoccupied molecular orbital (LUMO) and vibrational energy of the C-C stretching mode decreased with an increase in the metal-molecule distance. The molecular orbital energy shift and vibrational energy shift can be explained by the change in the degree of the hybridization of molecular and metal orbitals.

Investigation on the formation process of metal atomic filament for metal sulfide atomic switches by electrical measurement.

We have studied the formation process of the metal atomic filament for metal sulfide atomic switches by electrical measurement. The switching between ON and OFF states of the atomic switch is controlled by the application of the bias voltage for the atomic switches. The SET (OFF â†’ ON) and RESET (ON â†’ OFF) voltages were investigated for the atomic switch where the Ag2S or Cu2S layer were sandwiched between the Pt and Ag or Cu electrodes. The SET and RESET voltages of the Ag/Cu2S/Pt and Cu/Ag2S/Pt were close to those of the Ag/Ag2S/Pt atomic switch, and different from those of the Cu/Cu2S/Pt atomic switch. These results indicated that the dominant chemical species of the making and breaking part of the metal filament was Ag, and that the source of the metal filament was both the sulfide layer and the metal electrode.

Vortex rectenna powered by environmental fluctuations.

A rectenna, standing for a rectifying antenna, is an apparatus which generates d.c. electricity from electric fluctuations. It is expected to realize wireless power transmission as well as energy harvesting from environmental radio waves. To realize such rectification, devices that are made up of internal atomic asymmetry such as an asymmetric junction have been necessary so far. Here we report a material that spontaneously generates electricity by rectifying environmental fluctuations without using atomic asymmetry. The sample is a common superconductor without lowered crystalline symmetry, but, just by putting it in an asymmetric magnetic environment, it turns into a rectifier and starts generating electricity. Superconducting vortex strings only annihilate and nucleate at surfaces, and this allows the bulk electrons to feel surface fluctuations in an asymmetric environment: a vortex rectenna. The rectification and generation can be switched on and off with only a slight change in temperature or external magnetic fields.

Endogenous protein and enzyme fragments induce immunoglobulin E-independent activation of mast cells via a G protein-coupled receptor, MRGPRX2.

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through 2 main pathways, immunoglobulin E-dependent and E-independent activation. In the latter pathway, mast cells are activated by a diverse range of basic molecules (collectively known as basic secretagogues) through Mas-related G protein-coupled receptors (MRGPRs). In addition to the known basic secretagogues, here, we discovered several endogenous protein and enzyme fragments (such as chaperonin-10 fragment) that act as bioactive peptides and induce immunoglobulin E-independent mast cell activation via MRGPRX2 (previously known as MrgX2), leading to the degranulation of mast cells. We discuss the possibility that MRGPRX2 responds various as-yet-unidentified endogenous ligands that have specific characteristics, and propose that MRGPRX2 plays an important role in regulating inflammatory responses to endogenous harmful stimuli, such as protein breakdown products released from damaged or dying cells.

Aberrant accumulation of ErbB4 in progressive supranuclear palsy.

AIMS: The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP). METHODS: The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis. RESULTS: Whereas C-terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C-terminal ErbB4 in PSP. Double immunofluorescence for C-terminal ErbB4 and phospho-tau revealed co-localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N-terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons. CONCLUSIONS: Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.

Adjunctive perampanel in partial-onset seizures: Asia-Pacific, randomized phase III study.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of perampanel, a selective, non-competitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, as an adjunctive treatment for patients with refractory partial-onset seizures (POS) from Asia-Pacific. MATERIALS & METHODS: This multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT01618695) involved patients aged ≥12 years with refractory POS (receiving 1-3 antiepileptic drugs). Patients were randomized (1:1:1:1) to receive once-daily placebo or perampanel 4, 8, or 12 mg over a 6-week titration and 13-week maintenance double-blind period. Enzyme-inducing antiepileptic drugs were equally stratified between groups. The primary efficacy endpoint was percent change in POS frequency per 28 days (double-blind phase vs baseline). Other efficacy endpoints included ≥50% responder rate and seizure freedom. Treatment-emergent adverse events (TEAEs) were also monitored. RESULTS: Of 710 randomized patients, seizure frequency data were available for 704 patients. Median percent changes in POS frequency per 28 days indicated dose-proportional reductions in seizure frequency: -10.8% with placebo and -17.3% (P = .2330), -29.0% (P = .0003), and -38.0% (P < .0001) with perampanel 4, 8, and 12 mg, respectively. In total, 108 (15.3%) patients discontinued treatment; 44 (6.2%) due to TEAEs. TEAEs occurring in ≥5% of patients, and reported at least twice as frequently with perampanel vs placebo, included dizziness and irritability. CONCLUSIONS: Adjunctive perampanel (8 and 12 mg/d) significantly improved seizure control in patients with refractory POS. Safety and tolerability were acceptable at daily doses of perampanel 4-12 mg.

Kinematic analysis of pressing situations in female collegiate football games: New insight into anterior cruciate ligament injury causation.

The most common events during which anterior cruciate ligament (ACL) injuries occur in football are pressing situations. This study aimed to describe the knee and hip joint kinematics during pressing situations in football games to identify kinematic patterns in actions with a high risk for ACL injuries. We filmed 5 female collegiate football matches and identified 66 pressing situations. Five situations with a large distance between the trunk and foot placements in the sagittal plane were analyzed using a model-based image-matching technique. The mean knee flexion angle at initial contact (IC) was 13° (range, 8°-28°) and increased by 11° (95% confidence interval [CI], 3°-14°) at 40 ms after IC. As for knee adduction and rotation angles, the knee positions were close to neutral at IC, and only minor knee angular changes occurred later in the sequences. The mean hip flexion was 25° (range, 8°-43°) at IC and increased by 22° (95% CI, 11°-32°) after 100 ms. The hip was also externally rotated by 7° (range, -19° to 3°) at IC, and gradually rotated internally, reaching 10° of internal rotation (range, -5° to 27°) at 100 ms after IC. This study suggests that the observed knee valgus, internal hip and knee rotation, and static hip flexion previously reported in non-contact ACL injury events are unique to injury situations. In contrast, neither rapid knee valgus nor increased internal rotation was seen in non-injury pressing maneuvers.

Down-regulation of the two-component system and cell-wall biosynthesis-related genes was associated with the reversion to daptomycin susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus.

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

T-bet over-expression regulates aryl hydrocarbon receptor-mediated T helper type 17 differentiation through an interferon (IFN)γ-independent pathway.

Various transcription factors are also known to enhance or suppress T helper type 17 (Th17) differentiation. We have shown previously that the development of collagen-induced arthritis was suppressed in T-bet transgenic (T-bet Tg) mice, and T-bet seemed to suppress Th17 differentiation through an interferon (IFN)-γ-independent pathway, although the precise mechanism remains to be clarified. The present study was designed to investigate further the mechanisms involved in the regulation of Th17 differentiation by T-bet over-expression, and we found the new relationship between T-bet and aryl hydrocarbon receptor (AHR). Both T-bet Tg mice and IFN-γ-/- -over-expressing T-bet (T-bet Tg/IFN-γ-/- ) mice showed inhibition of retinoic acid-related orphan receptor (ROR)γt expression and IL-17 production by CD4+ T cells cultured under conditions that promote Th-17 differentiation, and decreased IL-6 receptor (IL-6R) expression and signal transducer and activator of transcription-3 (STAT-3) phosphorylation in CD4+ T cells. The mRNA expression of ahr and rorc were suppressed in CD4+ T cells cultured under Th-17 conditions from T-bet Tg mice and T-bet Tg/IFN-γ-/- mice. CD4+ T cells of wild-type (WT) and IFN-γ-/- mice transduced with T-bet-expressing retrovirus also showed inhibition of IL-17 production, whereas T-bet transduction had no effect on IL-6R expression and STAT-3 phosphorylation. Interestingly, the mRNA expression of ahr and rorc were suppressed in CD4+ T cells with T-bet transduction cultured under Th17 conditions. The enhancement of interleukin (IL)-17 production from CD4+ T cells by the addition of AHR ligand with Th17 conditions was cancelled by T-bet over-expression. Our findings suggest that T-bet over-expression-induced suppression of Th17 differentiation is mediated through IFN-γ-independent AHR suppression.

Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Atomic step-and-terrace surface of polyimide sheet for advanced polymer substrate engineering.

Typical thermostable and flexible polyimide polymers exhibit many excellent properties such as strong mechanical and chemical resistance. However, in contrast to single-crystal substrates like silicon or sapphire, polymers mostly display disordered and rough surfaces, which may result in instability and degradation of the interfaces between thin films and polymer substrates. As a step toward the development of next-generation polymer substrates, we here report single-atom-layer imprinting onto the polyimide sheets, resulting in an ultrasmooth 0.3 nm high atomic step-and-terrace surface on the polyimides. The ultrasmooth polymer substrates are expected to be applied to the fabrication of nanostructures such as superlattices, nanowires, or quantum dots in nanoscale-controlled electronic devices. We fabricate smooth and atomically stepped indium tin oxide transparent conducting oxide thin films on the imprinted polyimide sheets for future use in organic-based optoelectronic devices processed with nanoscale precision. Furthermore, toward 2D polymer substrate nanoengineering, we demonstrate nanoscale letter writing on the atomic step-and-terrace polyimide surface via atomic force microscopy probe scratching.

Teriparatide improves volumetric bone mineral density and fine bone structure in the UIV+1 vertebra, and reduces bone failure type PJK after surgery for adult spinal deformity.

We conducted a prospective comparative study of the effect of teriparatide therapy for preventing vertebral-failure-type PJK after reconstructive surgery for adult spinal deformity. Prophylactic teriparatide improved the volumetric bone mineral density and fine bone structure of the vertebra above the upper-instrumented vertebra and reduced the incidence of vertebral-failure-type PJK. INTRODUCTION: Proximal junctional kyphosis (PJK) is a complication after corrective surgery for spinal deformity. This study sought to determine whether teriparatide (TP) is an effective prophylactic against PJK type 2 (vertebral fracture) in surgically treated patients with adult spinal deformity (ASD). METHODS: Forty-three patients who started TP therapy immediately after surgery and 33 patients who did not receive TP were enrolled in this prospective case series. These patients were female, over 50, surgically treated for ASD, and followed for at least 2 years. Preoperative and postoperative standing whole-spine X-rays and dual-energy X-ray absorptiometry scans, and multidetector CT images obtained before and 6 months after surgery were used to analyze the bone strength in the vertebra above the upper-instrumented vertebra (UIV+1). RESULTS: Mean age was 67.9 years. After 6 months of treatment, mean hip-bone mineral density (BMD) increased from 0.721 to 0.771 g/cm2 in the TP group and decreased from 0.759 to 0.729 g/cm2 in the control group. This percent BMD change between groups was significant (p < 0.05). The volumetric BMD (326 to 366 mg/cm3) and bone mineral content (BMC) (553 to 622 mg) at UIV+1 were also significantly increased in TP group. The bone volume/tissue volume ratio increased from 46 to 54 % in the TP group, and the trabecular bone thickness and number increased by 14 and 5 %, respectively. At the 2-year follow-up, the PJK type 2 incidence was significantly lower in the TP group (4.6 %) than in the control group (15.2 %; p = .02). CONCLUSIONS: Prophylactic TP treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.