Investigating the Mechanisms Driving Referent Selection and Retention in Toddlers at Typical and Elevated Likelihood for Autism Spectrum Disorder.

It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., ). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words

Computational Method for Estimating DNA Copy Numbers in Normal Samples, Cancer Cell Lines, and Solid Tumors Using Array Comparative Genomic Hybridization

Genomic copy number variations are a typical feature of cancer. These variations may influence cancer outcomes as well as effectiveness of treatment. There are many computational methods developed to detect regions with deletions and amplifications without estimating actual copy numbers (CN) in these regions. We have developed a computational method capable of detecting regions with deletions and amplifications as well as estimating actual copy numbers in these regions. The method is based on determining how signal intensity from different probes is related to CN, taking into account changes in the total genome size, and incorporating into analysis contamination of the solid tumors with benign tissue. Hidden Markov Model is used to obtain the most likely CN solution. The method has been implemented for Affymetrix 500K GeneChip arrays and Agilent 244K oligonucleotide arrays. The results of CN analysis for normal cell lines, cancer cell lines, and tumor samples are presented. The method is capable of detecting copy number alterations in tumor samples with up to 80% contamination with benign tissue. Analysis of 178 cancer cell lines reveals multiple regions of common homozygous deletions and strong amplifications encompassing known tumor suppressor genes and oncogenes as well as novel cancer related genes

Structure Modeling of All Identified G Protein–Coupled Receptors in the Human Genome

G protein–coupled receptors (GPCRs), encoded by about 5% of human genes, comprise the largest family of integral membrane proteins and act as cell surface receptors responsible for the transduction of endogenous signal into a cellular response. Although tertiary structural information is crucial for function annotation and drug design, there are few experimentally determined GPCR structures. To address this issue, we employ the recently developed threading assembly refinement (TASSER) method to generate structure predictions for all 907 putative GPCRs in the human genome. Unlike traditional homology modeling approaches, TASSER modeling does not require solved homologous template structures; moreover, it often refines the structures closer to native. These features are essential for the comprehensive modeling of all human GPCRs when close homologous templates are absent. Based on a benchmarked confidence score, approximately 820 predicted models should have the correct folds. The majority of GPCR models share the characteristic seven-transmembrane helix topology, but 45 ORFs are predicted to have different structures. This is due to GPCR fragments that are predominantly from extracellular or intracellular domains as well as database annotation errors. Our preliminary validation includes the automated modeling of bovine rhodopsin, the only solved GPCR in the Protein Data Bank. With homologous templates excluded, the final model built by TASSER has a global C(α) root-mean-squared deviation from native of 4.6 Å, with a root-mean-squared deviation in the transmembrane helix region of 2.1 Å. Models of several representative GPCRs are compared with mutagenesis and affinity labeling data, and consistent agreement is demonstrated. Structure clustering of the predicted models shows that GPCRs with similar structures tend to belong to a similar functional class even when their sequences are diverse. These results demonstrate the usefulness and robustness of the in silico models for GPCR functional analysis. All predicted GPCR models are freely available for noncommercial users on our Web site (http://www.bioinformatics.buffalo.edu/GPCR)

Association Between Advanced Age and Vascular Disease in Different Arterial Territories A Population Database of Over 3.6 Million Subjects

ObjectivesThis study sought to determine the relationship between vascular disease in different arterial territories and advanced age.BackgroundVascular disease in the peripheral circulation is associated with significant morbidity and mortality. There is little data to assess the prevalence of different phenotypes of vascular disease in the very elderly.MethodsOver 3.6 million self-referred participants from 2003 to 2008 who completed a medical and lifestyle questionnaire in the United States were evaluated by screening ankle brachial indices <0.9 for peripheral artery disease (PAD), and ultrasound imaging for carotid artery stenosis (CAS) >50% and abdominal aortic aneurysm (AAA) >3 cm. Participants were stratified by decade of life. Multivariate logistic regression analysis was used to estimate odds of disease in different age categories.ResultsOverall, the prevalence of PAD, CAS, and AAA, was 3.7%, 3.9%, and 0.9%, respectively. Prevalence of any vascular disease increased with age (40 to 50 years: 2%, 51 to 60 years: 3.5%, 61 to 70 years: 7.1%, 71 to 80 years: 13.0%, 81 to 90 years: 22.3%, 91 to 100 years: 32.5%; p < 0.0001). Prevalence of disease in each vascular territory increased with age. After adjustment for sex, race/ethnicity, body mass index, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterolemia, and exercise, the odds of PAD (odds ratio [OR]: 2.14; 95% confidence interval [CI]: 2.12 to 2.15), CAS (OR: 1.80; 95% CI: 1.79 to 1.81), and AAA (OR: 2.33; 95% CI: 2.30 to 2.36) increased with every decade of life.ConclusionsThere is a dramatic increase in the prevalence of PAD, CAS, and AAA with advanced age. More than 20% and 30% of octogenarians and nonagenarians, respectively, have vascular disease in at least 1 arterial territory

On-chip interference of single photons from an embedded quantum dot and an external laser

In this work, we demonstrate the on-chip two-photon interference between single photons emitted by a single self-assembled InGaAs quantum dot and an external laser. The quantum dot is embedded within one arm of an air-clad directional coupler which acts as a beam-splitter for incoming light. Photons originating from an attenuated external laser are coupled to the second arm of the beam-splitter and then combined with the quantum dot photons, giving rise to two-photon quantum interference between dissimilar sources. We verify the occurrence of on-chip Hong-Ou-Mandel interference by cross-correlating the optical signal from the separate output ports of the directional coupler. This experimental approach allows us to use classical light source (laser) to assess in a single step the overall device performance in the quantum regime and probe quantum dot photon indistinguishability on application realistic time scales.Comment: 5 pages, 3 figure

Photon Statistics of Filtered Resonance Fluorescence

Spectral filtering of resonance fluorescence is widely employed to improve single photon purity and indistinguishability by removing unwanted backgrounds. For filter bandwidths approaching the emitter linewidth, complex behaviour is predicted due to preferential transmission of components with differing photon statistics. We probe this regime using a Purcell-enhanced quantum dot in both weak and strong excitation limits, finding excellent agreement with an extended sensor theory model. By changing only the filter width, the photon statistics can be transformed between antibunched, bunched, or Poissonian. Our results verify that strong antibunching and a sub-natural linewidth cannot simultaneously be observed, providing new insight into the nature of coherent scattering.Comment: Main manuscript 7 pages with 4 figures, supplementary material of 4 page

Observation of large spontaneous emission rate enhancement of quantum dots in a broken-symmetry slow-light waveguide

Quantum states of light and matter can be manipulated on the nanoscale to provide a technological resource for aiding the implementation of scalable photonic quantum technologies [1-3]. Experimental progress relies on the quality and efficiency of the coupling between photons and internal states of quantum emitters [4-6]. Here we demonstrate a nanophotonic waveguide platform with embedded quantum dots (QDs) that enables both Purcell-enhanced emission and strong chiral coupling. The design uses slow-light effects in a glide-plane photonic crystal waveguide with QD tuning to match the emission frequency to the slow-light region. Simulations were used to map the chirality and Purcell enhancement depending on the position of a dipole emitter relative to the air holes. The highest Purcell factors and chirality occur in separate regions, but there is still a significant area where high values of both can be obtained. Based on this, we first demonstrate a record large radiative decay rate of 17 ns^-1 (60 ps lifetime) corresponding to a 20 fold Purcell enhancement. This was achieved by electric-field tuning of the QD to the slow-light region and quasi-resonant phonon-sideband excitation. We then demonstrate a 5 fold Purcell enhancement for a dot with high degree of chiral coupling to waveguide modes, substantially surpassing all previous measurements. Together these demonstrate the excellent prospects for using QDs in scalable implementations of on-chip spin-photonics relying on chiral quantum optics.Comment: 15 pages, 4 figures, 1 table. Supporting information is available upon request to the corresponding autho

Interfacing a quantum dot spin with a photonic circuit

A scalable optical quantum information processor is likely to be a waveguide circuit with integrated sources, detectors, and either deterministic quantum-logic or quantum memory elements. With microsecond coherence times, ultrafast coherent control, and lifetime-limited transitions, semiconductor quantum-dot spins are a natural choice for the static qubits. However their integration with flying photonic qubits requires an on-chip spin-photon interface, which presents a fundamental problem: the spin-state is measured and controlled via circularly-polarised photons, but waveguides support only linear polarisation. We demonstrate here a solution based on two orthogonal photonic nanowires, in which the spin-state is mapped to a path-encoded photon, thus providing a blue-print for a scalable spin-photon network. Furthermore, for some devices we observe that the circular polarisation state is directly mapped to orthogonal nanowires. This result, which is physically surprising for a non-chiral structure, is shown to be related to the nano-positioning of the quantum-dot with respect to the photonic circuit