Entangled Photons from Small Quantum Dots

We discuss level schemes of small quantum-dot turnstiles and their applicability in the production of entanglement in two-photon emission. Due to the large energy splitting of the single-electron levels, only one single electron level and one single hole level can be made resonant with the levels in the conduction band and valence band. This results in a model with nine distinct levels, which are split by the Coulomb interactions. We show that the optical selection rules are different for flat and tall cylindrically symmetric dots, and how this affects the quality of the entanglement generated in the decay of the biexciton state. The effect of charge carrier tunneling and of a resonant cavity is included in the model.Comment: 10 pages, 8 figure

A marine isotope stage 11 coastal Acheulian workshop with associated wood at Amanzi Springs Area 1, South Africa

Amanzi Springs is a series of inactive thermal springs located near Kariega in the Eastern Cape of South Africa. Excavations in the 1960s exposed rare, stratified Acheulian-bearing deposits that were not further investigated over the next 50 years. Reanalysis of the site and its legacy collection has led to a redefined stratigraphic context for the archaeology, a confirmed direct association between Acheulian artefacts and wood, as well as the first reliable age estimates for the site. Thermally transferred optically stimulated luminescence and post-infrared infrared stimulated luminescence dating indicates that the Acheulian deposits from the Amanzi Springs Area 1 spring eye formed during Marine Isotope Stage (MIS) 11 at ~ 404-390 ka. At this time, higher sea levels of ~13-14m would have placed Amanzi Springs around 7 km from a ria that would have formed along what is today the Swartkops River, and which likely led to spring reactivation. This makes the Amanzi Springs Area 1 assemblage an unusual occurrence of a verified late occurring, seaward, open-air Acheulian occupation. The Acheulian levels do not contain any Middle Stone Age (MSA) elements such as blades and points that have been documented in the interior of South Africa at this time. However, a small number of stone tools from the upper layers of the artefact zone, and originally thought of as intrusive, have been dated to ~190 ka, at the transition between MIS 7 to 6, and represent the first potential MSA identified at the site.Andy I. R. HerriesID, Lee J. Arnold, Giovanni Boschian, Alexander F. Blackwood, Coen Wilson, Tom Mallett, Brian ArmstrongID, Martina DemuroID, Fiona Petchey, Matthew Meredith-Williams, Paul Penzo-Kajewski, Matthew V. Caruan

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

A marine isotope stage 13 Acheulian sequence from the Amanzi Springs Area 2 Deep Sounding excavation, Eastern Cape, South Africa.

Renewed research at Amanzi Springs has increased resolution on the timing and technology of the Acheulian industry in South Africa. The archeology from the Area 1 spring eye has recently been dated to MIS 11 (∼404-390 ka), and analyses revealed significant technological variability when compared to other southern African Acheulian assemblages. We expand on these results in presenting new luminescence dating and technological analyses of Acheulian stone tools from three artifact-bearing surfaces exposed within the White Sands unit of the Deep Sounding excavation in the Area 2 spring eye. The two lowest surfaces (Surfaces 3 and 2) are sealed within the White Sands and dated between ∼534 to 496 ka and ∼496 to 481 ka (MIS 13), respectively. Surface 1 represents materials deflated onto an erosional surface that cut the upper part of the White Sands (∼481 ka; late MIS 13), which occurred before the deposition of younger Cutting 5 sediments (<408-<290 ka; MIS 11-8). Archaeological comparisons reveal that the older Surface 3 and 2 assemblages are predominated by unifacial and bifacial core reduction and relatively thick, cobble-reduced large cutting tools. In contrast, the younger Surface 1 assemblage is characterized by discoidal core reduction and thinner large cutting tools, mostly made from flake blanks. Typological similarities between the older Area 2 White Sands and younger Area 1 (404-390 ka; MIS 11) assemblages further suggest long-term continuity in site function. We hypothesize Amanzi Springs represent a workshop locality that Acheulian hominins repeatedly visited to access unique floral, faunal, and raw material resources from at least ∼534 to 390 ka.Matthew V. Caruana, Coen G. Wilson, Lee J. Arnold, Alexander F. Blackwood, Martina Demuro, Andy I.R. Herrie