Production of heralded pure single photons from imperfect sources using cross phase modulation

Realistic single-photon sources do not generate single photons with certainty. Instead they produce statistical mixtures of photons in Fock states $\ket{1}$ and vacuum (noise). We describe how to eliminate the noise in the output of the sources by means of another noisy source or a coherent state and cross phase modulation (XPM). We present a scheme which announces the production of pure single photons and thus eliminates the vacuum contribution. This is done by verifying a XPM related phase shift with a Mach-Zehnder interferometer.Comment: 8 pages, 8 EPS figures, RevTeX4. Following changes have been made in v.3: Title and abstract slightly changed; numerous minor revisions and clarifications within the text; an appendix with three new figures has been added. In version v4 we have included a supplementary analysis of our scheme that takes into account absorption losses. Our analysis is heuristic and based on a phenomenological model, which is independent of the physical realization of the proposed scheme. We have estimated upper bounds up to which absorption losses can be tolerated, so as our scheme to improve the efficiency of single photon sources still works. Accepted for publication in Phys. Rev.

Heralded single-photon generation using imperfect single-photon sources and a two-photon-absorbing medium

We propose a setup for a heralded, i.e. announced generation of a pure single-photon state given two imperfect sources whose outputs are represented by mixtures of the single-photon Fock state $\ket{1}$ with the vacuum $\ket{0}$. Our purification scheme uses beam splitters, photodetection and a two-photon-absorbing medium. The admixture of the vacuum is fully eliminated. We discuss two potential realizations of the scheme.Comment: 22 pages, 8 figures (LaTeX). In version v2 we have slightly modified our setup so as to increase the success probability of single-photon generation by a factor of two. In addition, in an appendix we discuss alternative realizations of single-photon generation without a Mach-Zehnder interferometer. Three new figures have been added. Version v3 is a revised version published in Phys. Rev. A. It contains numerous minor corrections and clarifications. A new figure has been added in order to clarify our convention regarding labelling the field modes. The action of the beam splitters in the Schroedinger picture is introduced. A new reference has been include

Photon number resolving detection using time-multiplexing

Detectors that can resolve photon number are needed in many quantum information technologies. In order to be useful in quantum information processing, such detectors should be simple, easy to use, and be scalable to resolve any number of photons, as the application may require great portability such as in quantum cryptography. Here we describe the construction of a time-multiplexed detector, which uses a pair of standard avalanche photodiodes operated in Geiger mode. The detection technique is analysed theoretically and tested experimentally using a pulsed source of weak coherent light.Comment: 20 pages, 14 figures, accepted to Journal of Modern Optic

Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR

Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients

Potential for Powered Flight Neared by Most Close Avialan Relatives, but Few Crossed Its Thresholds

Uncertainties in the phylogeny of birds (Avialae) and their closest relatives have impeded deeper understanding of early theropod flight. To help address this, we produced an updated evolutionary hypothesis through an automated analysis of the Theropod Working Group (TWiG) coelurosaurian phylogenetic data matrix. Our larger, more resolved, and better-evaluated TWiG-based hypothesis supports the grouping of dromaeosaurids + troodontids (Deinonychosauria) as the sister taxon to birds (Paraves) and the recovery of Anchiornithinae as the earliest diverging birds. Although the phylogeny will continue developing, our current results provide a pertinent opportunity to evaluate what we know about early theropod flight. With our results and available data for vaned feathered pennaraptorans, we estimate the potential for powered flight among early birds and their closest relatives. We did this by using an ancestral state reconstruction analysis calculating maximum and minimum estimates of two proxies of powered flight potential—wing loading and specific lift. These results confirm powered flight potential in early birds but its rarity among the ancestors of the closest avialan relatives (select unenlagiine and microraptorine dromaeosaurids). For the first time, we find a broad range of these ancestors neared the wing loading and specific lift thresholds indicative of powered flight potential. This suggests there was greater experimentation with wing-assisted locomotion before theropod flight evolved than previously appreciated. This study adds invaluable support for multiple origins of powered flight potential in theropods (≥3 times), which we now know was from ancestors already nearing associated thresholds, and provides a framework for its further study. Video Abstract: [Figure presented] Pei et al. use an updated phylogeny of early birds and their closest relatives to reconstruct powered flight potential, showing it evolved at least three times. Many ancestors of the closest bird relatives neared thresholds of powered flight potential, suggesting broad experimentation with wing-assisted locomotion before theropod flight evolved.Fil: Pei, Rui. Institute Of Vertebrate Paleontology And Paleoanthropology Chinese Academy Of Sciences; ChinaFil: Pittman, Michael B.. The University Of Hong Kong; Hong KongFil: Goloboff, Pablo Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Dececchi, T. Alexander. Mount Marty College; Estados UnidosFil: Habib, Michael B.. Natural History Museum Of Los Angeles County; Estados UnidosFil: Kaye, Thomas G.. Foundation For Scientific Advancement; Estados UnidosFil: Larsson, Hans C. E.. Mcgill University; CanadáFil: Norell, Mark A.. American Museum of Natural History; Estados UnidosFil: Brusatte, Stephen L.. University of Edinburgh; Reino UnidoFil: Xu, Xing. Institute Of Vertebrate Paleontology And Paleoanthropology Chinese Academy Of Sciences; Chin

<em>MAPT </em>expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies

The MAPT (microtubule-associated protein tau) locus is one of the most remarkable in neurogenetics due not only to its involvement in multiple neurodegenerative disorders, including progressive supranuclear palsy, corticobasal degeneration, Parksinson's disease and possibly Alzheimer's disease, but also due its genetic evolution and complex alternative splicing features which are, to some extent, linked and so all the more intriguing. Therefore, obtaining robust information regarding the expression, splicing and genetic regulation of this gene within the human brain is of immense importance. In this study, we used 2011 brain samples originating from 439 individuals to provide the most reliable and coherent information on the regional expression, splicing and regulation of MAPT available to date. We found significant regional variation in mRNA expression and splicing of MAPT within the human brain. Furthermore, at the gene level, the regional distribution of mRNA expression and total tau protein expression levels were largely in agreement, appearing to be highly correlated. Finally and most importantly, we show that while the reported H1/H2 association with gene level expression is likely to be due to a technical artefact, this polymorphism is associated with the expression of exon 3-containing isoforms in human brain. These findings would suggest that contrary to the prevailing view, genetic risk factors for neurodegenerative diseases at the MAPT locus are likely to operate by changing mRNA splicing in different brain regions, as opposed to the overall expression of the MAPT gene

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients

INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. METHODS: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. RESULTS: After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7–3.9%), 10.7% (95% CI 6.3–14.9%), and 15.5% (95% CI 7.6–22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5–7.9%), 17.8% (95% CI 11.8–23.3%), and 19.9% (95% CI 14.2–25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. CONCLUSION: In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients

Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers

BACKGROUND: Inadequate oxygen (hypoxia) triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1α protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1α RNA in renal cells, and it could be diminished by reducing HIF-1α expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer

Probing the Functional Impact of Sequence Variation on p53-DNA Interactions Using a Novel Microsphere Assay for Protein-DNA Binding with Human Cell Extracts

The p53 tumor suppressor regulates its target genes through sequence-specific binding to DNA response elements (REs). Although numerous p53 REs are established, the thousands more identified by bioinformatics are not easily subjected to comparative functional evaluation. To examine the relationship between RE sequence variation—including polymorphisms—and p53 binding, we have developed a multiplex format microsphere assay of protein-DNA binding (MAPD) for p53 in nuclear extracts. Using MAPD we measured sequence-specific p53 binding of doxorubicin-activated or transiently expressed p53 to REs from established p53 target genes and p53 consensus REs. To assess the sensitivity and scalability of the assay, we tested 16 variants of the p21 target sequence and a 62-multiplex set of single nucleotide (nt) variants of the p53 consensus sequence and found many changes in p53 binding that are not captured by current computational binding models. A group of eight single nucleotide polymorphisms (SNPs) was examined and binding profiles closely matched transactivation capability tested in luciferase constructs. The in vitro binding characteristics of p53 in nuclear extracts recapitulated the cellular in vivo transactivation capabilities for eight well-established human REs measured by luciferase assay. Using a set of 26 bona fide REs, we observed distinct binding patterns characteristic of transiently expressed wild type and mutant p53s. This microsphere assay system utilizes biologically meaningful cell extracts in a multiplexed, quantitative, in vitro format that provides a powerful experimental tool for elucidating the functional impact of sequence polymorphism and protein variation on protein/DNA binding in transcriptional networks