216 research outputs found

    Heralded generation of entangled photon pairs

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    Entangled photons are a crucial resource for quantum communication and linear optical quantum computation. Unfortunately, the applicability of many photon-based schemes is limited due to the stochastic character of the photon sources. Therefore, a worldwide effort has focused in overcoming the limitation of probabilistic emission by generating two-photon entangled states conditioned on the detection of auxiliary photons. Here we present the first heralded generation of photon states that are maximally entangled in polarization with linear optics and standard photon detection from spontaneous parametric down-conversion. We utilize the down-conversion state corresponding to the generation of three photon pairs, where the coincident detection of four auxiliary photons unambiguously heralds the successful preparation of the entangled state. This controlled generation of entangled photon states is a significant step towards the applicability of a linear optics quantum network, in particular for entanglement swapping, quantum teleportation, quantum cryptography and scalable approaches towards photonics-based quantum computing

    Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

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    Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

    DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation.

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    Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array "waves", and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance

    The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

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    Although the murine immune response to Venezuelan equine encephalitis virus (VEEV) is well-characterized, little is known about the human antibody response to VEEV. In this study we used phage display technology to isolate a panel of 11 VEEV-specfic Fabs from two human donors. Seven E2-specific and four E1-specific Fabs were identified and mapped to five E2 epitopes and three E1 epitopes. Two neutralizing Fabs were isolated, E2-specific F5 and E1-specific L1A7, although the neutralizing capacity of L1A7 was 300-fold lower than F5. F5 Fab was expressed as a complete IgG1 molecule, F5 native (n) IgG. Neutralization-escape VEEV variants for F5 nIgG were isolated and their structural genes were sequenced to determine the theoretical binding site of F5. Based on this sequence analysis as well as the ability of F5 to neutralize four neutralization-escape variants of anti-VEEV murine monoclonal antibodies (mapped to E2 amino acids 182–207), a unique neutralization domain on E2 was identified and mapped to E2 amino acids 115–119

    Experimental One-Way Quantum Computing

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    Standard quantum computation is based on sequences of unitary quantum logic gates which process qubits. The one-way quantum computer proposed by Raussendorf and Briegel is entirely different. It has changed our understanding of the requirements for quantum computation and more generally how we think about quantum physics. This new model requires qubits to be initialized in a highly-entangled cluster state. From this point, the quantum computation proceeds by a sequence of single-qubit measurements with classical feedforward of their outcomes. Because of the essential role of measurement a one-way quantum computer is irreversible. In the one-way quantum computer the order and choices of measurements determine the algorithm computed. We have experimentally realized four-qubit cluster states encoded into the polarization state of four photons. We fully characterize the quantum state by implementing the first experimental four-qubit quantum state tomography. Using this cluster state we demonstrate the feasibility of one-way quantum computing through a universal set of one- and two-qubit operations. Finally, our implementation of Grover's search algorithm demonstrates that one-way quantum computation is ideally suited for such tasks.Comment: 36 pages, 6 figures, 2 table

    Night nursing – staff's working experiences

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    <p>Abstract</p> <p>Background</p> <p>Although the duties and working conditions of registered, and enrolled nurses have previously been described from different perspectives, they have not been examined from the night nursing aspect. The aim of the study was to describe the night nursing staff's working experiences.</p> <p>Methods</p> <p>The design of the study is qualitative and descriptive. Interviews were conducted with 10 registered and 10 enrolled nurses working as night staff at a Swedish University Hospital. The interview guide was thematic and concerned the content of their tasks, as well as the working conditions that constitute night nursing. In addition, the interviews were transcribed verbatim and analyzed using content analysis.</p> <p>Results</p> <p>The night duties have to be performed under difficult conditions that include working silently in dimmed lighting, and making decisions when fatigue threatens. According to the night staff, its main goals are to provide the patients with rest and simultaneously ensure qualified care. Furthermore, the night nursing staff must prepare the ward for the daytime activities.</p> <p>Conclusion</p> <p>The most important point is the team work, which developed between the registered and enrolled nurses and how necessary this team work is when working at night. In order for nurses working at night to be fully appreciated, the communication between day and night staff in health care organizations needs to be developed. Furthermore, it is important to give the night staff opportunities to use its whole field of competence.</p

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

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    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

    Alternative splicing of exon 10 in the tau gene as a target for treatment of tauopathies

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    Tau aggregation is one of the major features in Alzheimer's disease and in several other tauopathies, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), and progressive supranuclear palsy (PSP). More than 35 mutations in the tau gene have been identified from FTDP-17 patients. A group of these mutations alters splicing of exon 10, resulting in an increase in exon 10 inclusion into tau mRNA. Abnormal splicing with inclusion of exon 10 into tau mRNA has also been observed in PSP and AD patients. These results indicate that abnormal splicing of exon 10, leading to the production of tau with exon 10, is probably one of the mechanisms by which tau accumulates and aggregates in tauopathic brains. Therefore, modulation of exon 10 splicing in the tau gene could potentially be targeted to prevent tauopathies. To identify small molecules or compounds that could potentially be developed into drugs to treat tauopathies, we established a cell-based high-throughput screening assay. In this review, we will discuss how realistic, specific biological molecules can be found to regulate exon 10 splicing in the tau gene for potential treatment of tauopathies

    The effects of stimulus complexity on the preattentive processing of self-generated and nonself voices: an ERP study

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    The ability to differentiate one's own voice from the voice of somebody else plays a critical role in successful verbal self-monitoring processes and in communication. However, most of the existing studies have only focused on the sensory correlates of self-generated voice processing, whereas the effects of attentional demands and stimulus complexity on self-generated voice processing remain largely unknown. In this study, we investigated the effects of stimulus complexity on the preattentive processing of self and nonself voice stimuli. Event-related potentials (ERPs) were recorded from 17 healthy males who watched a silent movie while ignoring prerecorded self-generated (SGV) and nonself (NSV) voice stimuli, consisting of a vocalization (vocalization category condition: VCC) or of a disyllabic word (word category condition: WCC). All voice stimuli were presented as standard and deviant events in four distinct oddball sequences. The mismatch negativity (MMN) ERP component peaked earlier for NSV than for SGV stimuli. Moreover, when compared with SGV stimuli, the P3a amplitude was increased for NSV stimuli in the VCC only, whereas in the WCC no significant differences were found between the two voice types. These findings suggest differences in the time course of automatic detection of a change in voice identity. In addition, they suggest that stimulus complexity modulates the magnitude of the orienting response to SGV and NSV stimuli, extending previous findings on self-voice processing.This work was supported by Grant Numbers IF/00334/2012, PTDC/PSI-PCL/116626/2010, and PTDC/MHN-PCN/3606/2012, funded by the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and the Fundo Europeu de Desenvolvimento Regional through the European programs Quadro de Referencia Estrategico Nacional and Programa Operacional Factores de Competitividade, awarded to A.P.P., and by FCT Doctoral Grant Number SFRH/BD/77681/2011, awarded to T.C.info:eu-repo/semantics/publishedVersio
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