214 research outputs found

    Optomechanics with a position-modulated Kerr-type nonlinear coupling

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    Cavity optomechanics has proven to be a field of research rich with possibilities for studying motional cooling, squeezing, quantum entanglement, and metrology in solid-state systems. While to date most studies have focused on the modulation of the cavity frequency by the moving element, the emergence of new materials will soon allow us to explore the influences of nonlinear optical effects. We therefore study in this work the effects due to a nonlinear position-modulated self-Kerr interaction and find that this leads to an effective coupling that scales with the square of the photon number, meaning that significant effects appear even for very small nonlinearities. This strong effective coupling can lead to lower powers required for motional cooling and the appearance of multistability in certain regimes

    High real-space resolution measurement of the local structure of Ga_1-xIn_xAs using x-ray diffraction

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    High real-space resolution atomic pair distribution functions (PDF)s from the alloy series Ga_1-xIn_xAs have been obtained using high-energy x-ray diffraction. The first peak in the PDF is resolved as a doublet due to the presence of two nearest neighbor bond lengths, Ga-As and In-As, as previously observed using XAFS. The widths of nearest, and higher, neighbor pairs are analyzed by separating the strain broadening from the thermal motion. The strain broadening is five times larger for distant atomic neighbors as compared to nearest neighbors. The results are in agreement with model calculations.Comment: 4 pages, 5 figure

    Theoretical investigation of carbon defects and diffusion in Ξ±-quartz

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    The geometries, formation energies, and diffusion barriers of carbon point defects in silica (Ξ±-quartz) have been calculated using a charge-self-consistent density-functional based nonorthogonal tight-binding method. It is found that bonded interstitial carbon configurations have significantly lower formation energies (on the order of 5 eV) than substitutionals. The activation energy of atomic C diffusion via trapping and detrapping in interstitial positions is about 2.7 eV. Extraction of a CO molecule requires an activation energy <3.1 eV but the CO molecule can diffuse with an activation energy <0.4 eV. Retrapping in oxygen vacancies is hinderedβ€”unlike for O2β€”by a barrier of about 2 eV

    Mix of methods is needed to identify adverse events in general practice: A prospective observational study

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    Contains fulltext : 69425.pdf ( ) (Open Access)BACKGROUND: The validity and usefulness of incident reporting and other methods for identifying adverse events remains unclear. This study aimed to compare five methods in general practice. METHODS: In a prospective observational study, with five general practitioners, five methods were applied and compared. The five methods were physician reported adverse events, pharmacist reported adverse events, patients' experiences of adverse events, assessment of a random sample of medical records, and assessment of all deceased patients. RESULTS: A total of 68 events were identified using these methods. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. No overlap between the methods was detected. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. CONCLUSION: A mix of methods is needed to identify adverse events in general practice

    RIG-I Mediates Innate Immune Response in Mouse Neurons Following Japanese Encephalitis Virus Infection

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    Neuroinflammation associated with Japanese encephalitis (JE) is mainly due to the activation of glial cells with subsequent release of proinflammatory mediators from them. The recognition of viral RNA, in part, by the pattern recognition receptor retinoic acid-inducible gene I (RIG-I) has been indicated to have a role in such processes. Even though neurons are also known to express this receptor, its role after JE virus (JEV) infections is yet to be elucidated.Upon infecting murine neuroblastoma cells and primary cortical neurons with JEV the expression profile of key proinflammatory cyto/chemokines were analyzed by qRT-PCR and bead array, both before and after ablation of RIG-I. Immunoblotting was performed to evaluate the levels of key molecules downstream to RIG-I leading to production of proinflammatory mediators. Changes in the intracellular viral antigen expression were confirmed by intracellular staining and immunoblotting. JEV infection induced neuronal expression of IL-6, IL-12p70, MCP-1, IP-10 and TNF-Ξ± in a time-dependent manner, which showed significant reduction upon RIG-I ablation. Molecules downstream to RIG-I showed significant changes upon JEV-infection, that were modulated following RIG-I ablation. Ablation of RIG-I in neurons also increased their susceptibility to JEV.In this study we propose that neurons are one of the potential sources of proinflammatory cyto/chemokines in JEV-infected brain that are produced via RIG-I dependent pathways. Ablation of RIG-I in neurons leads to increased viral load and reduced release of the cyto/chemokines

    Genome-Scale Validation of Deep-Sequencing Libraries

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    Chromatin immunoprecipitation followed by high-throughput (HTP) sequencing (ChIP-seq) is a powerful tool to establish protein-DNA interactions genome-wide. The primary limitation of its broad application at present is the often-limited access to sequencers. Here we report a protocol, Mab-seq, that generates genome-scale quality evaluations for nucleic acid libraries intended for deep-sequencing. We show how commercially available genomic microarrays can be used to maximize the efficiency of library creation and quickly generate reliable preliminary data on a chromosomal scale in advance of deep sequencing. We also exploit this technique to compare enriched regions identified using microarrays with those identified by sequencing, demonstrating that they agree on a core set of clearly identified enriched regions, while characterizing the additional enriched regions identifiable using HTP sequencing

    Conserved Expression of the Glutamate NMDA Receptor 1 Subunit Splice Variants during the Development of the Siberian Hamster Suprachiasmatic Nucleus

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    Glutamate neurotransmission and the N-methyl-D-aspartate receptor (NMDAR) are central to photic signaling to the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). NMDARs also play important roles in brain development including visual input circuits. The functional NMDAR is comprised of multiple subunits, but each requiring the NR1 subunit for normal activity. The NR1 can be alternatively spliced to produce isoforms that confer different functional properties on the NMDAR. The SCN undergoes extensive developmental changes during postnatal life, including synaptogenesis and acquisition of photic signaling. These changes are especially important in the highly photoperiodic Siberian hamster, in which development of sensitivity to photic cues within the SCN could impact early physiological programming. In this study we examined the expression of NR1 isoforms in the hamster at different developmental ages. Gene expression in the forebrain was quantified by in situ hybridization using oligonucleotide probes specific to alternatively spliced regions of the NR1 heteronuclear mRNA, including examination of anterior hypothalamus, piriform cortex, caudate-putamen, thalamus and hippocampus. Gene expression analysis within the SCN revealed the absence of the N1 cassette, the presence of the C2 cassette alone and the combined absence of C1 and C2 cassettes, indicating that the dominant splice variants are NR1-2a and NR1-4a. Whilst we observe changes at different developmental ages in levels of NR1 isoform probe hybridization in various forebrain structures, we find no significant changes within the SCN. This suggests that a switch in NR1 isoform does not underlie or is not produced by developmental changes within the hamster SCN. Consistency of the NR1 isoforms would ensure that the response of the SCN cells to photic signals remains stable throughout life, an important aspect of the function of the SCN as a responder to environmental changes in quality/quantity of light over the circadian day and annual cycle

    Equity in utilization of antiretroviral therapy for HIV-infected people in South Africa: a systematic review

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    INTRODUCTION: About half a million people in South Africa are deprived of antiretroviral therapy (ART), and there is little systematic knowledge on who they are – e.g. by severity of disease, sex, or socio-economic status (SES). We performed a systematic review to determine the current quantitative evidence-base on equity in utilization of ART among HIV-infected people in South Africa. METHOD: We conducted a literature search based on the Cochrane guidelines. A study was included if it compared for different groups of HIV infected people (by sex, age, severity of disease, area of living, SES, marital status, ethnicity, religion and/or sexual orientation (i.e. equity criteria)) the number initiating/adhering to ART with the number who did not. We considered ART utilization inequitable for a certain criterion (e.g. sex) if between groups (e.g. men versus women) significant differences were reported in ART initiation/adherence. RESULTS: Twelve studies met the inclusion criteria. For sex, 2 out of 10 studies that investigated this criterion found that men are less likely than women to utilize ART, while the other 8 found no differences. For age, 4 out of 8 studies found inequities and reported less utilization for younger people. For area of living, 3 out of 4 studies showed that those living in rural areas or certain provinces have less access and 2 out of 6 studies looking at SES found that people with lower SES have less access. One study which looked at the marital status found that those who are married are less likely to utilize ART. For severity of disease, 5 out of 6 studies used more than one outcome measure for disease stage and reported within their study contradicting results. One of the studies reported inconclusive findings for ethnicity and no study had looked at religion and sexual orientation. CONCLUSION: It seems that men, young people, those living in certain provinces or rural areas, people who are unemployed or with a low educational level, and those being unmarried have less access to ART. As studies stem from different contexts and use different methods conclusions should be taken with caution

    Orphan CpG Islands Identify Numerous Conserved Promoters in the Mammalian Genome

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    CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are β€œorphans” that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development
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