606 research outputs found

    All Optical Implementation of Multi-Spin Entanglement in a Semiconductor Quantum Well

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    We use ultrafast optical pulses and coherent techniques to create spin entangled states of non-interacting electrons bound to donors (at least three) and at least two Mn2+ ions in a CdTe quantum well. Our method, relying on the exchange interaction between localized excitons and paramagnetic impurities, can in principle be applied to entangle a large number of spins.Comment: 17 pages, 3 figure

    Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

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    This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed ‘close-field electroporation’. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a ‘humanized’ neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies

    The Role of Early Life Experience and Species Differences in Alcohol Intake in Microtine Rodents

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    Social relationships have important effects on alcohol drinking. There are conflicting reports, however, about whether early-life family structure plays an important role in moderating alcohol use in humans. We have previously modeled social facilitation of alcohol drinking in peers in socially monogamous prairie voles. We have also modeled the effects of family structure on the development of adult social and emotional behaviors. Here we assessed whether alcohol intake would differ in prairie voles reared by both parents compared to those reared by a single mother. We also assessed whether meadow voles, a closely related species that do not form lasting reproductive partnerships, would differ in alcohol drinking or in the effect of social influence on drinking. Prairie voles were reared either bi-parentally (BP) or by a single mother (SM). BP- and SM-reared adult prairie voles and BP-reared adult meadow voles were given limited access to a choice between alcohol (10%) and water over four days and assessed for drinking behavior in social and non-social drinking environments. While alcohol preference was not different between species, meadow voles drank significantly lower doses than prairie voles. Meadow voles also had significantly higher blood ethanol concentrations than prairie voles after receiving the same dose, suggesting differences in ethanol metabolism. Both species, regardless of rearing condition, consumed more alcohol in the social drinking condition than the non-social condition. Early life family structure did not significantly affect any measure. Greater drinking in the social condition indicates that alcohol intake is influenced similarly in both species by the presence of a peer. While the ability of prairie voles to model humans may be limited, the lack of differences in alcohol drinking in BP- and SM-reared prairie voles lends biological support to human studies demonstrating no effect of single-parenting on alcohol abuse

    Hypoxia induces differential translation of enolase/MBP-1

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    <p>Abstract</p> <p>Background</p> <p>Hypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The α-enolase gene encodes both a glycolytic enzyme (α-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent α-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia. We have previously shown that MBP-1 and its binding to the c-myc P<sub>2 </sub>promoter regulates the metabolic and cellular growth changes that occur in response to altered exogenous glucose concentrations.</p> <p>Results</p> <p>To examine the regulation of α-enolase and MBP-1 by a hypoxic microenvironment in breast cancer, MCF-7 cells were grown in low, physiologic, or high glucose under 1% oxygen. Our results demonstrate that adaptation to hypoxia involves attenuation of MBP-1 translation and loss of MBP-1-mediated regulation of c-myc transcription, evidenced by decreased MBP-1 binding to the c-myc P<sub>2 </sub>promoter. This allows for a robust increase in c-myc expression, "early c-myc response", which stimulates aerobic glycolysis resulting in tumor acclimation to oxidative stress. Increased α-enolase mRNA and preferential translation/post-translational modification may also allow for acclimatization to low oxygen, particularly under low glucose concentrations.</p> <p>Conclusions</p> <p>These results demonstrate that malignant cells adapt to hypoxia by modulating α-enolase/MBP-1 levels and suggest a mechanism for tumor cell induction of the hyperglycolytic state. This important "feedback" mechanism may help transformed cells to escape the apoptotic cascade, allowing for survival during limited glucose and oxygen availability.</p

    Rapid decrease of malaria morbidity following the introduction of community-based monitoring in a rural area of central Vietnam

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    <p>Abstract</p> <p>Background</p> <p>Despite a successful control programme, malaria has not completely disappeared in Vietnam; it remains endemic in remote areas of central Vietnam, where standard control activities seem to be less effective. The evolution of malaria prevalence and incidence over two and half years in a rural area of central Vietnam, after the introduction of community-based monitoring of malaria cases, is presented.</p> <p>Methods</p> <p>After a complete census, six cross-sectional surveys and passive detection of malaria cases (by village and commune health workers using rapid diagnostic tests) were carried out between March 2004 and December 2006 in Ninh-Thuan province, in a population of about 10,000 individuals. The prevalence of malaria infection and the incidence of clinical cases were estimated.</p> <p>Results</p> <p>Malaria prevalence significantly decreased from 13.6% (281/2,068) in December 2004 to 4.0% (80/2,019) in December 2006. <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>were the most common infections with few <it>Plasmodium malariae </it>mono-infections and some mixed infections. During the study period, malaria incidence decreased by more than 50%, from 25.7/1,000 population at risk in the second half of 2004 to 12.3/1,000 in the second half of 2006. The incidence showed seasonal variations, with a yearly peak between June and December, except in 2006 when the peak observed in the previous years did not occur.</p> <p>Conclusion</p> <p>Over a 2.5-year follow-up period, malaria prevalence and incidence decreased by more than 70% and 50%, respectively. Possibly, this could be attributed to the setting up of a passive case detection system based on village health workers, indicating that a major impact on the malaria burden can be obtained whenever prompt diagnosis and adequate treatment are available.</p

    Transcriptome Analysis of the Vernalization Response in Barley (Hordeum vulgare) Seedlings

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    Temperate cereals, such as wheat (Triticum spp.) and barley (Hordeum vulgare), respond to prolonged cold by becoming more tolerant of freezing (cold acclimation) and by becoming competent to flower (vernalization). These responses occur concomitantly during winter, but vernalization continues to influence development during spring. Previous studies identified VERNALIZATION1 (VRN1) as a master regulator of the vernalization response in cereals. The extent to which other genes contribute to this process is unclear. In this study the Barley1 Affymetrix chip was used to assay gene expression in barley seedlings during short or prolonged cold treatment. Gene expression was also assayed in the leaves of plants after prolonged cold treatment, in order to identify genes that show lasting responses to prolonged cold, which might contribute to vernalization-induced flowering. Many genes showed altered expression in response to short or prolonged cold treatment, but these responses differed markedly. A limited number of genes showed lasting responses to prolonged cold treatment. These include genes known to be regulated by vernalization, such as VRN1 and ODDSOC2, and also contigs encoding a calcium binding protein, 23-KD jasmonate induced proteins, an RNase S-like protein, a PR17d secretory protein and a serine acetyltransferase. Some contigs that were up-regulated by short term cold also showed lasting changes in expression after prolonged cold treatment. These include COLD REGULATED 14B (COR14B) and the barley homologue of WHEAT COLD SPECIFIC 19 (WSC19), which were expressed at elevated levels after prolonged cold. Conversely, two C-REPEAT BINDING FACTOR (CBF) genes showed reduced expression after prolonged cold. Overall, these data show that a limited number of barley genes exhibit lasting changes in expression after prolonged cold treatment, highlighting the central role of VRN1 in the vernalization response in cereals

    ‘Other’ Posts in ‘Other’ Places: Poland through a Postcolonial Lens?

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    Postcolonial theory has tended to focus on those spaces where European colonialism has had a territorial and political history. This is unsurprising, as much of the world is in this sense ‘postcolonial’. But not all of it. This article focuses on Poland, often theorised as peripheral to ‘old Europe’, and explores the application of postcolonial analyses to this ‘other’ place. The article draws upon reflections arising from a study of responses to ethnic diversity in Warsaw, Poland. In doing so we conclude that postcolonialism does indeed offer some important insights into understanding Polish attitudes to other nationalities, and yet more work also needs to be done to make the theoretical bridge. In the case of Poland we propose the ‘triple relation’ be the starting point for such work

    Human Papillomavirus (HPV) 16 E6 Variants in Tonsillar Cancer in Comparison to Those in Cervical Cancer in Stockholm, Sweden

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    Background: Human papillomavirus (HPV), especially HPV16, is associated with the development of both cervical and tonsillar cancer and intratype variants in the amino acid sequence of the HPV16 E6 oncoprotein have been demonstrated to be associated with viral persistence and cancer lesions. For this reason the presence of HPV16 E6 variants in tonsillar squamous cell carcinoma (TSCC) in cervical cancer (CC), as well as in cervical samples (CS), were explored. Methods: HPV16 E6 was sequenced in 108 TSCC and 52 CC samples from patients diagnosed 2000–2008 in the County of Stockholm, and in 51 CS from young women attending a youth health center in Stockholm. Results: The rare E6 variant R10G was relatively frequent (19%) in TSCC, absent in CC and infrequent (4%) in CS, while the well-known L83V variant was common in TSCC (40%), CC (31%), and CS (29%). The difference for R10G was significant between TSCC and CC (p = 0.0003), as well as between TSCC and CS (p = 0.009). The HPV16 European phylogenetic lineage and its derivatives dominated in all samples (.90%). Conclusion: The relatively high frequency of the R10G variant in TSCC, as compared to what has been found in CC both in the present study as well as in several other studies in different countries, may indicate a difference between TSCC and CC with regard to tumor induction and development. Alternatively, there could be differences with regard to the oral an
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