High-fidelity initialization and control of electron and nuclear spins in a four-qubit register.

Single electron spins bound to multi-phosphorus nuclear spin registers in silicon have demonstrated fast (0.8 ns) two-qubit SWAP gates and long spin relaxation times (~30 s). In these spin registers, when the donors are ionized, the nuclear spins remain weakly coupled to their environment, allowing exceptionally long coherence times. When the electron is present, the hyperfine interaction allows coupling of the spin and charge degrees of freedom for fast qubit operation and control. Here we demonstrate the use of the hyperfine interaction to enact electric dipole spin resonance to realize high-fidelity ( F = 10 0 - 6 + 0 %) initialization of all the nuclear spins within a four-qubit nuclear spin register. By controllably initializing the nuclear spins to ⇓ ⇓ ⇓ , we achieve single-electron qubit gate fidelities of F = 99.78 ± 0.07% (Clifford gate fidelities of 99.58 ± 0.14%), above the fault-tolerant threshold for the surface code with a coherence time of T 2 * = 12 µ s .

The outer membrane Omp85-like protein P39 influences metabolic homeostasis in mature Arabidopsis thaliana.

The Omp85 proteins form a large membrane protein family in bacteria and eukaryotes. Omp85 proteins are composed of a C-terminal ß-barrel-shaped membrane domain and one or more N-terminal polypeptide transport-associated (POTRA) domains. However, Arabidopsis thaliana contains two genes coding for Omp85 proteins without a POTRA domain. One gene is designated P39, according to the molecular weight of the encoded protein. The protein is targeted to plastids and it was established that p39 has electrophysiological properties similar to other Omp85 family members, particularly to that designated as Toc75V/Oep80. We analysed expression of the gene and characterised two T-DNA insertion mutants, focusing on alterations in photosynthetic activity, plastid ultrastructure, global expression profile and metabolome. We observed pronounced expression of P39, especially in veins. Mutants of P39 show growth aberrations, reduced photosynthetic activity and changes in plastid ultrastructure, particularly in the leaf tip. Further, they display global alteration of gene expression and metabolite content in leaves of mature plants. We conclude that the function of the plastid-localised and vein-specific Omp85 family protein p39 is important, but not essential, for maintenance of metabolic homeostasis of full-grown A. thaliana plants. Further, the function of p39 in veins influences the functionality of other plant tissues. The link connecting p39 function with metabolic regulation in mature A. thaliana is discussed.

Economic Evaluation of a Pilot School-Based Dental Checkup Program.

The objectives of this study were to perform an economic evaluation of a targeted school-based dental checkup program in northern metropolitan Melbourne, Victoria. A 12-mo retrospective case-control cohort analysis using the decision tree method evaluated the incremental cost-utility and cost-effectiveness ratio (ICUR/ICER) for passive standard care dental services and an outreach pilot intervention completed in 2013. A societal perspective was adopted. A total of 273 children ( n = 273) aged between 3 and 12 y met the inclusion/exclusion criteria: 128 in the standard care group and 145 in the intervention group. The total society costs included health sector costs, patient/family costs, and productivity losses in 2014 Australian dollars. Outcome measures were evaluated using quality-adjusted tooth years (QATY) and the combined deciduous and permanent decayed, missing, and filled teeth prevented (DMFT-prevented). A generic outcome variable was created to determine the impact of the intervention to reach underserved populations based on government concession eligibility (cardholder status). Uncertainties were incorporated using 95% confidence intervals. The mean total society cost per child is $463 and $291 ( P = 0.002), QATY utility difference is 0.283 and 0.293 ( P = 0.937), effectiveness difference is 0.16 and 0.10 ( P = 0.756), and cardholder status is 50.0% and 66.2% ( P = 0.007), respectively, for the standard care and intervention groups. On average per child, there was a cost saving of $172 and improvement of 0.01 QATY, with an additional proportion of 16.2% of cardholder children reached. The calculated ICER was $3,252 per DMFT-prevented. The intervention dominates standard care for QATY and per 1% cardholder reached outcome measures. Our study found the pilot checkup program was largely less costly and more effective compared with the current standard care. Further research is needed to quantify the value of outreach interventions to prevent dental caries development and progression in populations from low socioeconomic status. Knowledge Transfer Statement: The findings of this research demonstrated that an outreach dental program can be less costly and more effective than standard models of dental care. It showed that a school-based dental checkup program is beneficial despite other opinions that dental screening is ineffective as a method to improve public dental health. There is fiscal economic evidence to support broader expansion of similar programs locally and internationally to reduce dental caries for children from low-income families.

Enabling high solubility of ZnO in TiO2 by nanolamination of atomic layer deposition.

Zn-doped TiO2 nanotubes were fabricated by nanolaminated packing of alternating layers of TiO2 and ZnO by atomic layer deposition (ALD) using a polycarbonate (PC) membrane as a template. With 400 cycles of ALD, the nanotubes with a thickness of 28 nm and an outer diameter of 220 nm were obtained after removing the PC membrane by annealing at 450 °C. The doping concentration of ZnO in TiO2 depends on the precursor cycle ratio of ZnO to TiO2. With the precursor cycle ratio of ZnO : TiO2 at 0.04, a uniform bulk solubility of ∼8 at% is obtained, and the surface concentration of Zn is even higher, ∼16 at%. From the depth profiles measured by secondary ion mass spectrometry, Zn is uniformly distributed across the thickness, which is further confirmed by analyses of X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectroscopy. Additionally, from the transmission electron microscopic observation, the highly doped anatase TiO2 exhibits some regions of severe deformation that results in localized solid-state amorphization.

Inhibition of peripheral blood natural killer cell cytotoxicity in patients with myasthenia gravis treated with plasmapheresis.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder that may involve natural killer (NK) cells. Although NK cells are part of the innate immune system, they also influence adaptive immune responses. Double-filtration plasmapheresis (DFP) is an effective therapy for MG crisis. Thus, we examined the effects of DFP on the cytotoxicity of NK cells. METHODS: A total of 20 patients with MG and 16 healthy controls were recruited for the study. Ficoll-Paque-isolated peripheral blood mononuclear cells (PBMCs) and K562 cells were used as the effector and target cells, respectively. NK cell cytotoxicity was analyzed using flow cytometry immediately before and after DFP and upon course completion. RESULTS: Double-filtration plasmapheresis treatment decreased significantly the NK cell cytotoxicity in patients with MG, especially in good responders, those who were positive for acetylcholine receptor (AChR) antibodies, and those receiving immunosuppressants. CONCLUSIONS: The decrease in NK cell cytotoxicity after DFP and the decline of AChR antibody titer were observed in good responders indicating that this could benefit patients with MG.

An atomic force microscope study of thermal behavior of phospholipid monolayers on mica.

We observed by using atomic force microscope (AFM) phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) monolayers on mica being annealed and cooled to a selection of temperatures through steps of 2-4 degrees C/min. The annealed phospholipid monolayers started to disappear at 45-50 degrees C and disappeared completely above 60-63 degrees C under AFM observation. The phospholipid monolayers reformed when the samples were cooled below 60 degrees C and developed from fractal into compact monolayer films with decreasing temperatures. Simultaneously the height of the reformed phospholipid films also increased with decreasing temperatures from 0.4 nm to the value before annealing. The observed thermal features are attributed to a phase-transition process that upon heating to above 45-50 degrees C, the lipids condensed in the monolayers transform into a low-density expanded phase in which the lipids are invisible to AFM, and the transformation continues and completes at 60-63 degrees C. The lipid densities of the expanded phase inferred from the dissociated area of the condensed phase are observed to be a function of the temperature. The behavior contrasts with a conventional first-order phase transition commonly seen in the Langmuir films. The temperature-dependent height and shape of the reformed phospholipid films during cooling are argued to arise from the adjustment of the packing and molecular tilting (with respect to the mica surface) of the phospholipids in order to accommodate more condensed phospholipids.

Universal behavior of membranes with sterols.

Lanosterol is the biosynthetic precursor of cholesterol and ergosterol, sterols that predominate in the membranes of mammals and lower eukaryotes, respectively. These three sterols are structurally quite similar, yet their relative effects on membranes have been shown to differ. Here we study the effects of cholesterol, lanosterol, and ergosterol on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipid bilayers at room temperature. Micropipette aspiration is used to determine membrane material properties (area compressibility modulus), and information about lipid chain order (first moments) is obtained from deuterium nuclear magnetic resonance. We compare these results, along with data for membrane-bending rigidity, to explore the relationship between membrane hydrophobic thickness and elastic properties. Together, such diverse approaches demonstrate that membrane properties are affected to different degrees by these structurally distinct sterols, yet nonetheless exhibit universal behavior.

Fasting stimulates tuberoinfundibular dopaminergic neuronal activity and inhibits prolactin secretion in oestrogen-primed ovariectomized rats: involvement of orexin A and neuropeptide Y.

Fasting up-regulates central orexigenic systems including orexin A and neuropeptide Y (NPY) and it also inhibits the secretion of prolactin. We hypothesized that fasting may act through orexin A and NPY to influence tuberoinfundibular dopaminergic (TIDA) neurones, the major regulator of prolactin secretion. The effects of orexin A and NPY on TIDA neuronal activity and prolactin secretion were determined in oestrogen-primed ovariectomized rats, and the effects of fasting and the involvement of orexin A and NPY were tested. Orexin A, NPY and its analogs were administered through preimplanted intracerebroventricular (i.c.v.) cannulae. TIDA neuronal activity was determined by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4-dihydroxyphenylalanine in the median eminence. i.c.v. injection of NPY (10 microg) or orexin A (1 microg) concomitantly increased median eminence DOPAC and decreased serum prolactin concentrations. The effect of NPY was mimicked by a Y1 receptor agonist at lower doses (0.1 and 1 microg) and no additive effect was observed when orexin A and the Y1 agaonist were coadministered. Moreover, a Y1 receptor antagonist, BIBP, not only blocked the effect of Y1 agaonist, but also that of orexin A. Treatment with BIBP alone decreased median eminence DOPAC and increased serum prolactin concentrations, indicating that endogenous NPY may play a role. Moreover, fasting for 48 h significantly increased TIDA neuronal activity, both in the morning and afternoon, and the effect was reversed by treatment with either BIBP or an antibody against orexin A. The findings support our hypothesis that fasting stimulates TIDA neuronal activity and inhibits prolactin secretion through up-regulated central orexin A and NPY systems.

Association of blood arsenic levels with increased reactive oxidants and decreased antioxidant capacity in a human population of northeastern Taiwan.

Arsenic is a notorious environmental toxicant known as both a carcinogen and an atherogen in human beings, but the pathogenic mechanisms are not completely understood. In cell culture studies, trivalent arsenic enhanced oxidative stress in a variety of mammalian cells, and this association may be closely associated with the development of arsenic-related diseases. To investigate the effect of arsenic exposure on oxidative stress in humans, we conducted a population study to determine the relationships of blood arsenic to reactive oxidants and antioxidant capacity at the individual level. We recruited 64 study subjects ages 42-75 years from residents of the Lanyang Basin on the northeast coast of Taiwan, where arsenic content in well water varies from 0 to > or = 3,000 microg/L. We used a chemiluminescence method, with lucigenin as an amplifier for measuring superoxide, to measure the plasma level of reactive oxidants. We used the azino-diethyl-benzthiazoline sulphate method to determine the antioxidant capacity level in plasma of each study subject. We determined arsenic concentration in whole blood by hydride formation with an atomic absorption spectrophotometer. The average arsenic concentration in whole blood of study subjects was 9.60 +/- 9.96 microg/L (+/- SD) with a range from 0 to 46.50 microg/L. The level of arsenic concentration in whole blood of study subjects showed a positive association with the level of reactive oxidants in plasma (r = +0.41, p = 0.001) and an inverse relationship with the level of plasma antioxidant capacity (r = -0.30, p = 0.014). However, we found no significant association (p = 0.266) between levels of plasma reactive oxidants and antioxidant capacity. Our results also show that the lower the primary arsenic methylation capability, the lower the level of plasma antioxidant capacity (p = 0.029). These results suggest that ingestion of arsenic-contaminated well water may cause deleterious effects by increasing the level of reactive oxidants and decreasing the level of antioxidant capacity in plasma of individuals. Persistent oxidative stress in peripheral blood may be a mechanism underlying the carcinogenesis and atherosclerosis induced by long-term arsenic exposure.

Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans.

The neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein (neurofibromin). Although it is known to possess Ras GTPase-activating protein (GAP) activity, the cellular role of neurofibromin remains unclear. Here we used yeast two-hybrid screening to identify neurofibromin-interacting proteins. Syndecan-2, a transmembrane heparan sulfate proteoglycan (HSPG), was isolated as a binding partner for two distinct regions of the neurofibromin protein. We subsequently found that neurofibromin can bind all four mammalian syndecans. NF1 interaction requires the transmembrane domain and a membrane-proximal region of the cytoplasmic tail of syndecan, but not the C terminus of syndecan known to bind to CASK, a membrane-associated guanylate kinase (MAGUK). Neurofibromin, syndecans, and CASK have overlapping subcellular distributions in axons and synapses of neurons, as shown by biochemical fractionation and immunostaining. Moreover, neurofibromin exists in a complex with syndecan and CASK in vivo, as evidenced by their coimmunoprecipitation from rat brain. Our findings suggest that interaction with different members of the syndecan family may be a mechanism for localizing neurofibromin to specialized domains of the plasma membrane.

Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids, antioxidant enzyme activities and bone density.

OBJECTIVE: To investigate isoflavone supplementation on plasma lipids, erythrocyte antioxidant enzyme activities and bone mineral density in postmenopausal women. STUDY DESIGN: Thirty-seven postmenopausal women were given 150 mg/d of isoflavone supplements twice daily for six months. Blood was sampled before and after supplementation, at three and six months. RESULTS: There were no significant differences in plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride concentrations or erythrocyte antioxidant enzyme activities after three and six months of supplementation when compared with the baseline. No significant changes were noted in calcaneus bone mineral density after supplementing isoflavones for six months. CONCLUSION: The antioxidant effect of isoflavones in normal postmenopausal women is not obvious, and supplementation with isoflavone alone may not have a hypocholesterolemic effect. Since the duration of this study was too short with respect to bone density, longer studies are needed to clarify the bone-sparing effect of isoflavone supplementation.

Tbr1 regulates differentiation of the preplate and layer 6.

During corticogenesis, early-born neurons of the preplate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections. Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had molecular and functional defects. Cajal-Retzius cells expressed decreased levels of Reelin, resulting in a reeler-like cortical migration disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic determinant for the differentiation of early-born glutamatergic neocortical neurons and provide insights into the functions of these neurons as regulators of cortical development.

Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90.

Members of the postsynaptic density-95 (PSD-95)/SAP90 family of membrane-associated guanylate kinase (MAGUK) proteins function as multimodular scaffolds that organize protein-signaling complexes at neuronal synapses. MAGUK proteins contain PDZ, Src homology 3 (SH3), and guanylate kinase (GK)-like domains, all of which can function as sites for specific protein-protein interactions. We report here a direct protein-protein interaction between the SH3 domain and the GK region in the PSD-95 family of MAGUKs. The SH3 domain of the PSD-95 family appears to have an atypical binding specificity, because the classical SH3 binding (-P-X-X-P-) motif is absent from the GK domain. Although SH3-GK binding can occur in either an intramolecular or intermolecular manner, the intramolecular mode is preferred, possibly because of additional tertiary interactions available when the SH3 and GK domains are adjacent in the same polypeptide. Mutations disrupting the intramolecular SH3-GK interaction do not interfere with PSD-95 association with the K(+) channel Kv1.4 or with the GK domain-binding protein GKAP. The same mutations, however, inhibit the clustering of Kv1.4 by PSD-95, suggesting that the intramolecular SH3-GK interaction may modulate the clustering activity of PSD-95.

Negative regulation of expression of the Bacillus megaterium bmlP1 gene by the bmlP1 3' flanking region.

We report that the expression of the Bacillus megaterium bmlP1 gene is subject to negative regulation by the bmlP1 3' flanking region. This repression occurred both in B. megaterium and in Escherichia coli. When the bmlP1 promoter was replaced with a heterologous promoter or when the orientation of the bmlP1 3' flanking region was reversed, the inhibitory effect was still observed. However, the bmlP1 3' flanking region was unable to exert repression on a heterologous gene when fused downstream in either orientation, and it was incapable of acting in trans. Dot blot and Northern blot analyses revealed that the repression occurred at the RNA level. Deletion analysis showed that the regulatory site responsible for the repression is located within a 116-bp region immediately following the bmlP1 gene. Possible mechanisms for this repression are discussed.

Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2.

Membrane-associated guanylate kinases (MAGUKs) contain multiple protein-binding domains that allow them to assemble specific multiprotein complexes in particular regions of the cell. CASK/LIN-2, a MAGUK required for EGF receptor localization and signalling in Caenorhabditis elegans, contains a calmodulin-dependent protein kinase-like domain followed by PDZ, SH3 and guanylate kinase-like domains. In adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins neurexin and syndecan and the cytoplasmic proteins Mint/LIN-10 and Veli/LIN-7. Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development. CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. Our findings show that a MAGUK which is usually associated with cell junctions has a transcription regulation function.