Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

Correlation Differences in Heartbeat Fluctuations During Rest and Exercise

We study the heartbeat activity of healthy individuals at rest and during exercise. We focus on correlation properties of the intervals formed by successive peaks in the pulse wave and find significant scaling differences between rest and exercise. For exercise the interval series is anticorrelated at short time scales and correlated at intermediate time scales, while for rest we observe the opposite crossover pattern -- from strong correlations in the short-time regime to weaker correlations at larger scales. We suggest a physiologically motivated stochastic scenario to explain the scaling differences between rest and exercise and the observed crossover patterns.Comment: 4 pages, 4 figure

The Bridgwater Infant Welfare Centre, 1922-1939: from an authoritarian concern with 'welfare mothers' to a more inclusive community health project?

The infant welfare movement in Britain has received considerable scholarly attention but continues to generate controversy and debate. Many of the services began with nineteenth-century voluntary initiative but were later developed by local authorities. Critics have drawn attention to the limitations of such provision; arguing that it was predicated on unattractive assumptions about class and gender roles. Under this interpretation working-class mothers were viewed with suspicion and targeted for advice aimed at inculcating middle-class standards of childcare and housekeeping. This paper accepts that there was an authoritarian character to much of the early welfare work but suggests that over time this gave way to more inclusive approaches that sought to provide clients with the services that met their real rather than assumed needs. This paper reviews the recent historiography, develops an overview of national trends, and then takes a detailed look at the Bridgwater Infant Welfare Centre. The case study benefi ts from unusually comprehensive records and, by drawing on evidence from a small Somerset town, adds to our understanding of infant welfare work that has previously been developed from research on major urban centres.Wellcome Trust Fellowshi

Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPSc from sporadic Creutzfeldt-Jakob disease

In recent studies, the amyloid form of recombinant prion protein (PrP) encompassing residues 89–230 (rPrP 89-230) produced in vitro induced transmissible prion disease in mice. These studies showed that unlike “classical” PrPSc produced in vivo, the amyloid fibrils generated in vitro were more proteinase-K sensitive. Here we demonstrate that the amyloid form contains a proteinase K-resistant core composed only of residues 152/153–230 and 162–230. The PK-resistant fragments of the amyloid form are similar to those observed upon PK digestion of a minor subpopulation of PrPSc recently identified in patients with sporadic Creutzfeldt-Jakob disease (CJD). Remarkably, this core is sufficient for self-propagating activity in vitro and preserves a β-sheet-rich fibrillar structure. Full-length recombinant PrP 23-230, however, generates two subpopulations of amyloid in vitro: One is similar to the minor subpopulation of PrPSc, and the other to classical PrPSc. Since no cellular factors or templates were used for generation of the amyloid fibrils in vitro, we speculate that formation of the subpopulation of PrPSc with a short PK-resistant C-terminal region reflects an intrinsic property of PrP rather than the influence of cellular environments and/or cofactors. Our work significantly increases our understanding of the biochemical nature of prion infectious agents and provides a fundamental insight into the mechanisms of prions biogenesis

Prion protein expression in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system

10 pagesSyrian hamster prion protein (PrPc) and a truncated Syrian hamster prion protein lacking the glycosylphosphatidylinositol (GPI) anchor C-terminal signal sequence (GPI~) were expressed in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system. The CHO cell clones expressing the GPI" PrP secreted the majority of the protein into the media, whereas most of the PrP produced by clones expressing the full-length protein with the GPI anchor was located on the cell surface, as demonstrated by its release upon treatment with phosphatidylinositol-specific phospholipase C (PIPLC). A cell clone that expressed the highest levels of full length PrP was subcloned to obtain clone 30C3-1. PrP from clone 30C3-1 was shown to be sensitive to proteolysis by proteinase K and to react with monoclonal and polyclonal antibodies that recognize native PrPc. The recombinant PrP migrated as a diffuse band of 19-40 kDa but removal of the N-linked oligosaccharides with peptide N-glycosidase F (PNGase F) revealed three protein species of 19, 17 and 15 kDa. The 19 kDa band corresponding to deglycosylated full-length PrP was quantified and found to be expressed at a level - 14-fold higher than that of PrPc found in Syrian hamster brain

A surface code quantum computer in silicon

The exceptionally long quantum coherence times of phosphorus donor nuclear spin qubits in silicon, coupled with the proven scalability of silicon-based nano-electronics, make them attractive candidates for large-scale quantum computing. However, the high threshold of topological quantum error correction can only be captured in a two-dimensional array of qubits operating synchronously and in parallel—posing formidable fabrication and control challenges. We present an architecture that addresses these problems through a novel shared-control paradigm that is particularly suited to the natural uniformity of the phosphorus donor nuclear spin qubit states and electronic confinement. The architecture comprises a two-dimensional lattice of donor qubits sandwiched between two vertically separated control layers forming a mutually perpendicular crisscross gate array. Shared-control lines facilitate loading/unloading of single electrons to specific donors, thereby activating multiple qubits in parallel across the array on which the required operations for surface code quantum error correction are carried out by global spin control. The complexities of independent qubit control, wave function engineering, and ad hoc quantum interconnects are explicitly avoided. With many of the basic elements of fabrication and control based on demonstrated techniques and with simulated quantum operation below the surface code error threshold, the architecture represents a new pathway for large-scale quantum information processing in silicon and potentially in other qubit systems where uniformity can be exploited

Multiple-Surrogate Approach to Helicopter Rotor Blade Vibration Reduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77383/1/AIAA-40291-933.pd