A MEMS Light Modulator Based on Diffractive Nanohole Gratings

We present the design, fabrication, and testing of a microelectromechanical systems (MEMS) light modulator based on pixels patterned with periodic nanohole arrays. Flexure-suspended silicon pixels are patterned with a two dimensional array of 150 nm diameter nanoholes using nanoimprint lithography. A top glass plate assembled above the pixel array is used to provide a counter electrode for electrostatic actuation. The nanohole pattern is designed so that normally-incident light is coupled into an in-plane grating resonance, resulting in an optical stop-band at a desired wavelength. When the pixel is switched into contact with the top plate, the pixel becomes highly reflective. A 3:1 contrast ratio at the resonant wavelength is demonstrated for gratings patterned on bulk Si substrates. The switching time is 0.08 ms and the switching voltage is less than 15V

Retinol esterification in Sertoli cells by lecithin-retinol acyltransferase

Esterification of retinol occurs during the metabolism of vitamin A in the testis. An acyl- CoA:retinol acyltransferase (ARAT) activity has been described for microsomes isolated from testis homogenates. That activity was also observed here in microsomal preparations obtained from cultured Sertoli cells from 20-day-old (midpubertal) rats. ARAT catalyzed the synthesis of retinyl laurate when free retinol and lauroyl-CoA were provided as substrates. However, in the absence of exogenous acyl-CoA, retinol was esterified by a different activity in a manner similar to the lecithimretinol acyltransferase (LRAT) activity described recently for liver and intestine. Microsomal preparations obtained from enriched Sertoli cell fractions from the adult rat testis had 75-fold higher levels of LRAT than the preparations from midpubertal animals, but ARAT activity was the same in both these preparations. LRAT utilized an endogenous acyl donor and either unbound retinol or retinol complexed with cellular retinol-binding protein (CRBP) to catalyze the synthesis of retinyl linoleate, retinyl oleate, retinyl palmitate, and retinyl stearate. The addition of exogenous dilaurylphosphatidylcholine (DLPC) resulted in the synthesis of retinyl laurate. The esterification from both exogenous DLPC and endogenous acyl donor was inhibited by 2 mM phenylmethanesulfonyl fluoride (PMSF). ARAT activity was not affected by similar concentrations of PMSF. Furthermore, retinol bound to CRBP, a protein known to be present in Sertoli cells, was not an effective substrate for testicular ARAT. When retinol uptake and metabolism were examined in cultured Sertoli cells from 20-day-old rats, the cells synthesized the same retinyl esters that were produced by microsomal LRAT in vitro. Pretreating the cells with PMSF did not prevent specific retinol accumulation but did inhibit retinol esterification. Consequently, the LRAT-like retinyl esters produced by cultured Sertoli cells and the sensitivity of this esterification to PMSF suggest that LRAT, and not ARAT, is the physiologically important retinyl ester synthase in the Sertoli cell

Characteristics of retinol accumulation from serum retinol-binding protein by cultured Sertoli cells

The uptake of retinol was examined in cultured Sertoli cells when retinol was provided as a complex with the transport protein retinol-binding protein (RBP). Sertoli cells accumulated [3H]retinol in a time- and temperature-dependent manner. At 32 °C, the rate of retinol accumulation was biphasic. Accumulation was linear for approximately 1 h, but then accumulation continued at a linear but decreased rate for 23 h. The change in rate of retinol accumulation occurred when the cells had accumulated approximately 0.53 pmol of retinol/Mg of cellular DNA. This amount of retinol was approximately equal to the cellular content of cellular retinol-binding protein (CRBP). Extraction and HPLC analysis of the cell-associated radioactivity yielded retinol and retinyl esters, indicating that a significant proportion of the accumulated retinol was esterified. Excess unlabeled retinol-RBP competed with [3H]retinol-RBP for [3H]retinol delivery to the cells, indicating that RBP delivery of retinol was a saturable and competable process. However, free [3H]retinol associated with Sertoli cells in a noncompetable manner. The transport constant for specific retinol accumulation from RBP was 3.0 μ , suggesting that any change in the normal circulating retinol-RBP level (approximately 2 μ ) would directly affect the rate of retinol accumulation. Neither iodinated nor reductively methylated RBP was accumulated by or tightly bound to Sertoli cells. In addition, energy inhibitors and lysosomal poisons had no effect on [3H] retinol accumulation, indicating that RBP delivery of retinol to Sertoli cells did not occur by endocytosis of the retinol-RBP complex. Competition studies indicated, however, that protein recognition is important in the retinol uptake process. RBP, CRBP, and CRBP(II) competed with [3H] retinol-RBP for [3H] retinol accumulation, but free retinol, retinol-bovine serum albumin, and retinol-/3-lactoglobulin did not. Transthyretin, bound to [3H] retinol-RBP in the physiological 1:1 ratio, decreased [3H]retinol accumulation by the cells by 25-30% compared to [3H]retinol accumulation from [3H]retinol-RBP. These studies indicated that Sertoli cell uptake of retinol involved recognition of the retinol-RBP complex at the cell surface with subsequent internalization of retinol, but not RBP. The fate of the internalized retinol may first have involved binding by CRBP, but eventually a significant portion of the accumulated retinol was esterified

Detection of skewed X-chromosome inactivation in Fragile X syndrome and X chromosome aneuploidy using quantitative melt analysis.

Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility

Association of Alcohol Consumption with Perception of Attractiveness in a Naturalistic Environment

AIMS: To investigate the relationship between objectively-assessed alcohol consumption and perception of attractiveness in naturalistic drinking environments, and to determine the feasibility and acceptability of conducting a large-scale study in these environments. METHODS: Observational study conducted simultaneously across three public houses in Bristol, UK. Participants were required to rate the attractiveness of male and female face stimuli and landscape stimuli administered via an Android tablet computer application, after which their expired breath alcohol concentration (BrAC) was measured. RESULTS: Linear regression revealed no clear evidence for relationships between alcohol consumption and either overall perception of attractiveness for stimuli, for faces specifically, or for opposite-sex faces. The naturalistic research methodology was feasible, with high levels of participant engagement and enjoyment. CONCLUSIONS: We found no evidence for a relationship between alcohol consumption and perception of attractiveness in our large-scale naturalistic study. Our study is important given the large sample size, the successful translation of an experimental, laboratory-based paradigm to a naturalistic drinking environment and the high level of public engagement with the study. Future studies should use similarly ecologically-valid methodologies to further explore the conditions under which this effect may be observed and identify the mechanisms underlying any relationships

An Euler system for GU(2, 1)

We construct an Euler system associated to regular algebraic, essentially conjugate self-dual cuspidal automorphic representations of GL3 over imaginary quadratic fields, using the cohomology of Shimura varieties for GU(2,1)

Fabrication of a Large, Ordered, Three-Dimensional Nanocup Array

Metallic nanocups provide a unique method for redirecting scattered light by creating magnetic plasmon responses at optical frequencies. Despite considerable development of nanocup fabrication processes, simultaneously achieving accurate control over the placement, orientation, and geometry of nanocups has remained a significant challenge. Here we present a technique for fabricating large, periodically ordered arrays of uniformly oriented three-dimensional gold nanocups for manipulating light at subwavelength scales. Nanoimprint lithography, soft lithography, and shadow evaporation were used to fabricate nanocups onto the tips of polydimethylsiloxane nanopillars with precise control over the shapes and optical properties of asymmetric nanocups

Evolution of South Atlantic density and chemical stratification across the last deglaciation.

Explanations of the glacial-interglacial variations in atmospheric pCO2 invoke a significant role for the deep ocean in the storage of CO2. Deep-ocean density stratification has been proposed as a mechanism to promote the storage of CO2 in the deep ocean during glacial times. A wealth of proxy data supports the presence of a "chemical divide" between intermediate and deep water in the glacial Atlantic Ocean, which indirectly points to an increase in deep-ocean density stratification. However, direct observational evidence of changes in the primary controls of ocean density stratification, i.e., temperature and salinity, remain scarce. Here, we use Mg/Ca-derived seawater temperature and salinity estimates determined from temperature-corrected δ(18)O measurements on the benthic foraminifer Uvigerina spp. from deep and intermediate water-depth marine sediment cores to reconstruct the changes in density of sub-Antarctic South Atlantic water masses over the last deglaciation (i.e., 22-2 ka before present). We find that a major breakdown in the physical density stratification significantly lags the breakdown of the deep-intermediate chemical divide, as indicated by the chemical tracers of benthic foraminifer δ(13)C and foraminifer/coral (14)C. Our results indicate that chemical destratification likely resulted in the first rise in atmospheric pCO2, whereas the density destratification of the deep South Atlantic lags the second rise in atmospheric pCO2 during the late deglacial period. Our findings emphasize that the physical and chemical destratification of the ocean are not as tightly coupled as generally assumed.We are grateful to I. Mather, J. Rolfe, F. Dewilde and G. Isguder for preparing and performing isotopic analyses, as well as C. Daunt, S. Souanef-Ureta and M. Greaves for technical assistance in performing trace element analysis. J.R. was funded jointly by the British Geological Survey/British Antarctic Survey (Natural Environment Research Council) and the University of Cambridge. J.G. was funded by the Gates Cambridge Trust. L.C.S. acknowledges support from the Royal Society and NERC grant NE/J010545/1. C.W. acknowledges support from the European Research Council grant ACCLIMATE/no 339108. This is LSCE contribution 5514. This work was funded (in part) by the European Research Council (ERC grant 2010-NEWLOG ADG-267931 HE). N.V.R. acknowledges support from EU RTN NICE (no. 36127). We thank the captain and crew of the RRS James Clark Ross for facilitating the collection of the marine sediment core GC528.This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.151125211

Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens

The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 Plasmodium falciparum proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that IgG reactivity was significantly higher to extracellular and plasma membrane proteins and also correlated positively with both protein abundance and degree of protein polymorphism. Conversely, IgG reactivity was significantly lower to proteins predicted to have human orthologs. These findings provide insight into protein-specific factors that are associated with variability in the magnitude of antibody responses to natural P. falciparum infection-data that could inform vaccine strategies to optimize antibody-mediated immunity as well as the selection of antigens for sero-diagnostic purposes