Silicon Atomic Quantum Dots Enable Beyond-CMOS Electronics

We review our recent efforts in building atom-scale quantum-dot cellular automata circuits on a silicon surface. Our building block consists of silicon dangling bond on a H-Si(001) surface, which has been shown to act as a quantum dot. First the fabrication, experimental imaging, and charging character of the dangling bond are discussed. We then show how precise assemblies of such dots can be created to form artificial molecules. Such complex structures can be used as systems with custom optical properties, circuit elements for quantum-dot cellular automata, and quantum computing. Considerations on macro-to-atom connections are discussed.Comment: 28 pages, 19 figure

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Human lactobacilli as supplementation of clindamycin to patients with bacterial vaginosis reduce the recurrence rate; a 6-month, double-blind, randomized, placebo-controlled study

<p>Abstract</p> <p>Background</p> <p>The primary objective of this study was to investigate if supplementary lactobacilli treatment could improve the initial cure rate after vaginal clindamycin therapy, and secondly, if lactobacilli as repeated adjunct treatment during 3 menstrual cycles could lengthen the time to relapse after initial cure.</p> <p>Methods</p> <p>Women (n = 100) with bacterial vaginosis diagnosed by Amsel criteria were after informed consent offered vaginal clindamycin therapy followed by vaginal gelatine capsules containing either 10⁹freeze-dried lactobacilli or identical placebo capsules for 10 days during 3 menstrual cycles in a double-blind, randomized, placebo-controlled trial.</p> <p>Results</p> <p>The initial intent to treat (ITT) analysis for the one-month cure rate was 64% in the lactobacilli group and 78% in the placebo group (p > 0.05). However, any patient with missing or unclassified smears at the initial visit who continued the study and whose next smear indicated a cure was included in the cured group; the study also excluded two of the patients in the lactobacilli group who reported that they did not take any vaginal capsules. With consideration to these population changes, the initial cure rate would be 77% in the lactobacilli group. The 76 cured women were followed for 6 menstrual cycles or until relapse within that time span. At the end of the study, 64.9% (24/37) of the lactobacilli treated women were still BV-free compared to 46.2% (18/39) of the placebo treated women. Comparison of the two groups regarding "Time from cure to relapse" was statistically significant (p = 0.027) in favour of the lactobacilli treatment. Adjuvant therapy with lactobacilli contributed significantly to avoidance of relapse with a proportional Hazard Risk ratio (HR) of 0.73 (0.54–0.98) (p < 0.05)</p> <p>Conclusion</p> <p>The study shows that supplementary treatment combining two different strains of probiotic lactobacilli does not improve the efficacy of BV therapy during the first month of treatment, but for women initially cured, adjunct treatment of lactobacilli during 3 menstrual cycles lengthens the time to relapse significantly in that more women remained BV free at the end of the 6-month follow up.</p> <p>Trial registration number</p> <p>ISRCTN62879834</p

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

BACKGROUND: Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy) is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. METHODS: Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796) who were initiated during the study on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276). The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. RESULTS: During the 1-year period, only a third (35.7%) of the patients were treated predominately with monotherapy (>300 days). Most patients (57.7%) had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days). Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043) or quetiapine (p = .002). The number of monotherapy days was significantly greater for olanzapine than quetiapine (p < .001), but not for olanzapine versus risperidone, or for risperidone versus quetiapine-initiated patients. CONCLUSION: Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic polypharmacy for prolonged periods is very common during the treatment of schizophrenia patients in usual care settings. In addition, in this non-randomized naturalistic observational study, the most commonly used atypical antipsychotics significantly differed on the rate and duration of antipsychotic monotherapy. Reasons for and the impact of the predominant use of polypharmacy will require further study

Did Corporate Governance Compliance Have an Impact on Auditor Selection and Quality? Evidence From FTSE 350

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.This paper examines the possible effects of corporate governance (GC) on audit quality (AQ) among the FTSE 350 companies. Using a sample of 180 companies from 2012 to 2017 (i.e., 1080 firm-year observations) a binary logistic model has been employed to investigate the CG-AQ nexus. This analysis was supported by conducting a probit logistic model as a sensitivity analysis. Our findings are associative of a heterogeneous impact of CG on AQ post the implementation of the 2012 CG reforms in the UK. For example, although institutional ownership and management ownership are positively associated with auditor selection and AQ, board independence, non-executive directors and audit committee are not attributed to AQ in the UK. This implies that corporate compliance with good CG practices has a limited impact on the decision to select a Big4 auditor in the UK. Despite the limitations of our study, we hope it can motivate further investigations in this area

Origin of Secretin Receptor Precedes the Advent of Tetrapoda: Evidence on the Separated Origins of Secretin and Orexin

At present, secretin and its receptor have only been identified in mammals, and the origin of this ligand-receptor pair in early vertebrates is unclear. In addition, the elusive similarities of secretin and orexin in terms of both structures and functions suggest a common ancestral origin early in the vertebrate lineage. In this article, with the cloning and functional characterization of secretin receptors from lungfish and X. laevis as well as frog (X. laevis and Rana rugulosa) secretins, we provide evidence that the secretin ligand-receptor pair has already diverged and become highly specific by the emergence of tetrapods. The secretin receptor-like sequence cloned from lungfish indicates that the secretin receptor was descended from a VPAC-like receptor prior the advent of sarcopterygians. To clarify the controversial relationship of secretin and orexin, orexin type-2 receptor was cloned from X. laevis. We demonstrated that, in frog, secretin and orexin could activate their mutual receptors, indicating their coordinated complementary role in mediating physiological processes in non-mammalian vertebrates. However, among the peptides in the secretin/glucagon superfamily, secretin was found to be the only peptide that could activate the orexin receptor. We therefore hypothesize that secretin and orexin are of different ancestral origins early in the vertebrate lineage

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

<i>Cis</i> P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI