Surface-state Coulomb repulsion accelerates a metal-insulator transition in topological semimetal nanofilms.

The emergence of quantization at the nanoscale, the quantum size effect (QSE), allows flexible control of matter and is a rich source of advanced functionalities. A QSE-induced transition into an insulating phase in semimetallic nanofilms was predicted for bismuth a half-century ago and has regained new interest with regard to its surface states exhibiting nontrivial electronic topology. Here, we reveal an unexpected mechanism of the transition by high-resolution angle-resolved photoelectron spectroscopy combined with theoretical calculations. Anomalous evolution and degeneracy of quantized energy levels indicate that increased Coulomb repulsion from the surface states deforms a quantum confinement potential with decreasing thickness. The potential deformation strongly modulates spatial distributions of quantized wave functions, which leads to acceleration of the transition beyond the original QSE picture. This discovery establishes a complete picture of the long-discussed transition and highlights a new class of size effects dominating nanoscale transport in systems with metallic surface states.

DUSP1 promotes senescence of retinoblastoma cell line SO-Rb5 cells by activating AKT signaling pathway.

OBJECTIVE: Retinoblastoma seriously threats to human health and life. Molecular targeted therapy of retinoblastoma supplies the direction of research in the future. This study aims to investigate the impact of DUSP1 on human retinoblastoma SO-Rb5 cell senescence. MATERIALS AND METHODS: Angiotensin II (AGII) was used to induce human retinoblastoma SO-Rb5 cell senescence model. DUSP1 over-expression plasmid and small interfere RNA (siRNA) were transfected into SO-Rb5 cells by Lipofectamine. Dual specificity phosphatase 1 (DUSP1), p53, p16, and protein kinase B (Akt) signaling expressions were detected with Western blot assay. SH-6 was applied to inhibit Akt signaling in SO-Rb5 cells. Cell senescence was evaluated by using ß-galactosidase test. RESULTS: DUSP1 level increased in SO-Rb5 cells induced by AGII. Senescence protein p53 and p16 significantly upregulated in SO-Rb5 cell senescence model, together with ß-galactosidase staining. DUSP1 plasmid transfection significantly enhanced DUSP expression, triggered SO-Rb5 cell senescence, and inhibited Akt signaling activation. DUSP1 siRNA exhibited the opposite effects. SH-6 significantly increased SO-Rb5 cell senescence induced by AGII through inhibiting Akt signaling. CONCLUSIONS: DUSP1 facilitated human retinoblastoma SO-Rb5 cell senescence induced by AGII through inhibiting Akt signaling pathway.

Two-dimensional electronic transport and surface electron accumulation in MoS2.

Because the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface because of the absence of dangling bonds. However, here we show that the surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n-doping source. The surface electron concentration of MoS2 is nearly four orders of magnitude higher than that of its inner bulk. Substantial thickness-dependent conductivity in MoS2 nanoflakes was observed. The transfer length method suggested the current transport in MoS2 following a two-dimensional behavior rather than the conventional three-dimensional mode. Scanning tunneling microscopy and angle-resolved photoemission spectroscopy measurements confirmed the presence of surface electron accumulation in this layered material. Notably, the in situ-cleaved surface exhibited a nearly intrinsic state without electron accumulation.

Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Anisotropy in the thermal hysteresis of resistivity and charge density wave nature of single crystal SrFeO3-δ: X-ray absorption and photoemission studies.

The local electronic and atomic structures of the high-quality single crystal of SrFeO3-δ (δ~0.19) were studied using temperature-dependent x-ray absorption and valence-band photoemission spectroscopy (VB-PES) to investigate the origin of anisotropic resistivity in the ab-plane and along the c-axis close to the region of thermal hysteresis (near temperature for susceptibility maximum, Tm~78 K). All experiments herein were conducted during warming and cooling processes. The Fe L 3,2-edge X-ray linear dichroism results show that during cooling from room temperature to below the transition temperature, the unoccupied Fe 3d e g states remain in persistently out-of-plane 3d 3z2-r2 orbitals. In contrast, in the warming process below the transition temperature, they change from 3d 3z2-r2 to in-plane 3d x2-y2 orbitals. The nearest-neighbor (NN) Fe-O bond lengths also exhibit anisotropic behavior in the ab-plane and along the c-axis below Tm. The anisotropic NN Fe-O bond lengths and Debye-Waller factors stabilize the in-plane Fe 3d x2-y2 and out-of-plane 3d 3z2-r2 orbitals during warming and cooling, respectively. Additionally, a VB-PES study further confirms that a relative band gap opens at low temperature in both the ab-plane and along the c-axis, providing the clear evidence of the charge-density-wave nature of SrFeO3-δ (δ~0.19) single crystal.

Electronic and atomic structures of the Sr3Ir4Sn13 single crystal: A possible charge density wave material.

X-ray scattering (XRS), x-ray absorption near-edge structure (XANES) and extended x-ray absorption fine structure (EXAFS) spectroscopic techniques were used to study the electronic and atomic structures of the high-quality Sr3Ir4Sn13 (SIS) single crystal below and above the transition temperature (T* ≈ 147 K). The evolution of a series of modulated satellite peaks below the transition temperature in the XRS experiment indicated the formation of a possible charge density wave (CDW) in the (110) plane. The EXAFS phase derivative analysis supports the CDW-like formation by revealing different bond distances [Sn1(2)-Sn2] below and above T* in the (110) plane. XANES spectra at the Ir L3-edge and Sn K-edge demonstrated an increase (decrease) in the unoccupied (occupied) density of Ir 5d-derived states and a nearly constant density of Sn 5p-derived states at temperatures T < T* in the (110) plane. These observations clearly suggest that the Ir 5d-derived states are closely related to the anomalous resistivity transition. Accordingly, a close relationship exists between local electronic and atomic structures and the CDW-like phase in the SIS single crystal.

Proving Nontrivial Topology of Pure Bismuth by Quantum Confinement.

The topology of pure Bi is controversial because of its very small (∼10 meV) band gap. Here we perform high-resolution angle-resolved photoelectron spectroscopy measurements systematically on 14-202 bilayer Bi films. Using high-quality films, we succeed in observing quantized bulk bands with energy separations down to ∼10 meV. Detailed analyses on the phase shift of the confined wave functions precisely determine the surface and bulk electronic structures, which unambiguously show nontrivial topology. The present results not only prove the fundamental property of Bi but also introduce a capability of the quantum-confinement approach.

The common CARD14 gene missense polymorphism rs11652075 (c.C2458T/p.Arg820Trp) is associated with psoriasis: a meta-analysis.

Recent genetic evidence suggests a robust association of the CARD14 single nucleotide polymorphism rs11652075 (c.C2458T/p.Arg820Trp) and other rare mutations in this gene with psoriasis. To assess whether combined data support the relationship between CARD14 rs11652075 and susceptibility to this disease, we conducted a meta-analysis. PubMed (MEDLINE), EMBASE, Web of Science, and the Cochrane Library were searched for relevant papers published in English. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effect models. Heterogeneity between studies was assessed using the Cochran's Q and I2 statistics. A total of five published studies, including 32,807 psoriasis patients and 45,458 controls, met our inclusion criteria and were included in the meta-analysis. The pooled OR of the association between the minor allele of this polymorphism and psoriasis was 0.877 (95%CI = 0.834-0.922; P < 0.001). In a stratified analysis, pooled ORs relating to European and Asian ancestry were 0.883 (95%CI = 0.822-0.948) and 0.872 (95%CI = 0.812-0.936), respectively. Those calculated for studies with case sample sizes above and below 1000 were 0.912 (95%CI = 0.870- 0.956) and 0.824 (95%CI = 0.734-0.924), respectively. No publication bias was present, and the exclusion of any single dataset did not substantially alter the corresponding pooled ORs. Due to the limited data available regarding clinical classification of cases and genotypes, subgroup stratification by clinical type was not performed. Our results demonstrate a significant association between the CARD14 rs11652075 polymorphism and psoriasis.

Development of a millimetrically scaled biodiesel transesterification device that relies on droplet-based co-axial fluidics.

In this study, we investigated a fluidic system that adheres to new concepts of energy production. To improve efficiency, cost, and ease of manufacture, a millimetrically scaled device that employs a droplet-based co-axial fluidic system was devised to complete alkali-catalyzed transesterification for biodiesel production. The large surface-to-volume ratio of the droplet-based system, and the internal circulation induced inside the moving droplets, significantly enhanced the reaction rate of immiscible liquids used here - soybean oil and methanol. This device also decreased the molar ratio between methanol and oil to near the stoichiometric coefficients of a balanced chemical equation, which enhanced the total biodiesel volume produced, and decreased the costs of purification and recovery of excess methanol. In this work, the droplet-based co-axial fluidic system performed better than other methods of continuous-flow production. We achieved an efficiency that is much greater than that of reported systems. This study demonstrated the high potential of droplet-based fluidic chips for energy production. The small energy consumption and low cost of the highly purified biodiesel transesterification system described conforms to the requirements of distributed energy (inexpensive production on a moderate scale) in the world.

Association between atopic dermatitis-related single nucleotide polymorphisms rs4722404 and psoriasis vulgaris in a southern Chinese cohort.

Genome-wide association studies have identified a single nucleotide polymorphism (SNP), rs4722404, in the caspase recruitment domain family member 11 (CARD11) gene, which is associated with atopic dermatitis. Previous genetic studies have also reported genomic similarities between psoriasis and atopic dermatitis. However, little is known regarding the association between rs4722404 and psoriasis vulgaris (PsV). The aim of this study was to evaluate the relationship between rs4722404 and the risk and clinical features of PsV in a southern Chinese Han cohort. This hospital-based case-control study included 355 patients with PsV and 213 control subjects (N = 568); the samples were analyzed using a standard SNaPshot assay. We identified no association between the SNP and risk of PsV. However, a stratified analysis according to the age of onset, family history, and psoriasis area and severity index sub-phenotypes revealed a significant correlation between the C allele and CC+CT genotype of rs4722404 and an increased risk of early-onset PsV (≤40 years) compared to that of late-onset PsV (>40 years) (odds ratio, OR = 1.486; P = 0.026 for C allele and OR = 1.718, P = 0.023 for CC+CT genotype). The results of this study suggested that the SNP rs4722404 in CARD11 could increase the risk of early-onset PsV. Further studies must analyze the potential function of CARD11 in the pathogenesis of PsV.

Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study.

BACKGROUND: A cross-sectional retrospective study suggested a link between allergic diseases and Parkinson's disease. However, the temporal association between asthma and Parkinson's disease remains unknown. METHODS: From the Taiwan National Health Insurance Research Database, 10 455 patients who were diagnosed with asthma between 1998 and 2008 and aged ≥45 years and 41 820 age- and sex-matched controls were selected for our study and observed until the end of 2011. Those who developed Parkinson's disease during the follow-up period were identified. We also examined the asthma severity, as indicated by the frequency of admission (times per year) for asthma exacerbation, and the risk of subsequent Parkinson's disease. RESULTS: Patients with asthma had an increased risk of developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval [CI]: 2.20-4.36) after we adjusted for demographic data, health system use, medical comorbidities, and medication use. Sensitivity tests yielded consistent findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04-4.13) and first 3 years (HR: 2.46, 95% CI: 1.64-3.69). Patients with asthma who had more frequent admissions (times per year) during the follow-up period exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95% CI: 5.88-45.91; 1-2: 12.69, 95% CI: 5.03-31.71; 0-1: HR: 2.92, 95% CI: 1.91-4.49). CONCLUSION: Patients with asthma had an elevated risk of developing Parkinson's disease later in life, and we observed a dose-dependent relationship between greater asthma severity and a higher risk of subsequent Parkinson's disease.

Anomalous spectral features of a neutral bilayer graphene.

Graphene and its bilayer are two-dimensional systems predicted to show exciting many-body effects near the neutrality point. The ideal tool to investigate spectrum reconstruction effects is angle-resolved photoemission spectroscopy (ARPES) as it probes directly the band structure with information about both energy and momentum. Here we reveal, by studying undoped exfoliated bilayer graphene with ARPES, two essential aspects of its many-body physics: the electron-phonon scattering rate has an anisotropic k-dependence and the type of electronic liquid is non-Fermi liquid. The latter behavior is evident from an observed electron-electron scattering rate that scales linearly with energy from 100 meV to 600 meV and that is associated with the proximity of bilayer graphene to a two-dimensional quantum critical point of competing orders.

Snapshots of Dirac fermions near the Dirac point in topological insulators.

The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.

Expression of ß-glucuronidase on the surface of bacteria enhances activation of glucuronide prodrugs.

Extracellular activation of hydrophilic glucuronide prodrugs by ß-glucuronidase (ßG) was examined to increase the therapeutic efficacy of bacteria-directed enzyme prodrug therapy (BDEPT). ßG was expressed on the surface of Escherichia coli by fusion to either the bacterial autotransporter protein Adhesin (membrane ßG (mßG)/AIDA) or the lipoprotein (lpp) outermembrane protein A (mßG/lpp). Both mßG/AIDA and mßG/lpp were expressed on the bacterial surface, but only mßG/AIDA displayed enzymatic activity. The rate of substrate hydrolysis by mßG/AIDA-BL21cells was 2.6-fold greater than by pßG-BL21 cells, which express periplasmic ßG. Human colon cancer HCT116 cells that were incubated with mßG/AIDA-BL21 bacteria were sensitive to a glucuronide prodrug (p-hydroxy aniline mustard ß-D-glucuronide, HAMG) with an half maximal inhibitory concentration (IC50) value of 226.53±45.4 µM, similar to the IC50 value of the active drug (p-hydroxy aniline mustard, pHAM; 70.6±6.75 µM), indicating that mßG/AIDA on BL21 bacteria could rapidly and efficiently convert HAMG to an active anticancer agent. These results suggest that surface display of functional ßG on bacteria can enhance the hydrolysis of glucuronide prodrugs and may increase the effectiveness of BDEPT.

CHMP6 and VPS4A mediate the recycling of Ras to the plasma membrane to promote growth factor signaling.

While Ras is well-known to function on the plasma membrane (PM) to mediate growth factor signaling, increasing evidence suggests that Ras has complex roles in the cytoplasm. To uncover these roles, we screened a cDNA library and isolated H-Ras-binding proteins that also influence Ras functions. Many isolated proteins regulate trafficking involving endosomes; CHMP6/VPS20 and VPS4A, which interact with ESCRT-III (Endosomal Sorting Complex Required for Transport-III), were chosen for further study. We showed that the binding is direct and occurs in endosomes. Furthermore, the binding is most efficient when H-Ras has a functional effector-binding loop, and is GTP-bound and ubiquitylated. CHMP6 and VPS4A also bound to N-Ras but not K-Ras. Repressing CHMP6 and VPS4A blocked Ras-induced transformation, which correlated with inefficient Ras localization to the PM as measured by cell fractionation and photobleaching. Moreover, silencing CHMP6 and VPS4A also blocked epidermal growth factor receptor (EGFR) recycling. These data suggest that Ras interacts with key ESCRT-III components to promote recycling of itself and EGFR back to the PM to create a positive feedback loop to enhance growth factor signaling.

Study of gastric fluid induced cytokine and chemokine expression in airway smooth muscle cells and airway remodeling.

Asthma is a chronic airway inflammatory disease. Chronic aspiration by gastric fluid in gastroesophageal reflux disease (GERD) is considered a primary inflammatory factor exacerbating or predisposing patients to asthma. Airway smooth muscle cells (SMCs) are considered an important component in airway remodeling. To investigate the role of gastric fluid in airway SMC inflammation and airway remodeling, we examined gastric fluid-induced cytokine and chemokine profiles, airway SMC migration and matrix metalloproteinase expression in rat primary rat airway SMCs. The T helper cell type 2 (Th2) cytokines interleukin 4, interleukin 6 and tumor necrosis factor 2 (TNF-α) and the chemokines, lipopolysaccharide-induced CXC chemokine (LIX/CXCL5), cytokine-induced neutrophil chemoattractant 2 (CINC-2), CINC-3, fractalkine, ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor were induced by gastric fluid in primary cultured rat airway SMCs. Migration of rat airway SMCs was enhanced by gastric fluid and conditioned medium. The migration of rat airway SMCs enhanced by gastric fluid was associated with actin polymerization and activation of focal adhesion kinase. Matrix metalloproteinase 2 expressions in airway SMCs was enhanced by gastric fluid and conditioned medium. The results suggest potential mechanisms by which gastric fluid aspiration might influence SMC-mediated airway remodeling.

Hospital systems for the detection and prevention of adverse drug events.

In its 2006 report "Preventing Medication Errors," the Institute of Medicine (IOM) estimated that more than 1.5 million preventable adverse drug events (ADEs) occur annually in the United States. Many organizations, including the IOM, the Institute for Safe Medication Practices, the US Food and Drug Administration, and the Leap Frog Group for Patient Safety have advocated the implementation of technologies to reduce ADEs, particularly in the hospital setting. Many technologies have emerged in recent years to reduce ADEs at various points in the medication use process; however, interfacing some of these key technologies with existing hospital systems poses significant challenges.

Optimal electron doping of a C60 monolayer on Cu(111) via interface reconstruction.

We demonstrate the charge state of C60 on a Cu(111) surface can be made optimal, i.e., forming C60(3-) as required for superconductivity in bulk alkali-doped C60, purely through interface reconstruction rather than with foreign dopants. We link the origin of the C60(3-) charge state to a reconstructed interface with ordered (4x4) 7-atom vacancy holes in the surface. In contrast, C60 adsorbed on unreconstructed Cu(111) receives a much smaller amount of electrons. Our results illustrate a definitive interface effect that affects the electronic properties of molecule-electrode contact.

Novel electronic structure induced by a highly strained oxide interface with incommensurate crystal fields.

The misfit oxide, Bi2Ba1.3K0.6Co2.1O7.94, made of alternating rocksalt-structured [BiO/BaO] layers and hexagonal CoO2 layers, was studied by angle-resolved photoemission spectroscopy, revealing the electronic structure of a highly strained oxide interface. We found that low-energy states are confined within individual sides of the interface, but scattered by the incommensurate crystal field from the other side. Furthermore, the high strain on the rocksalt layer induces large charge transfer to the CoO2 layer, and a novel effect, the interfacial enhancement of electron-phonon interactions, is discovered.