Development of N/P AlGaAs free-standing top solar cells for tandem applications

The combination of a free standing AlGaAs top solar cell and an existing bottom solar cell is the highest performance, lowest risk approach to implementing the tandem cell concept. The solar cell consists of an AlGaAs substrate layer, an AlGaAs base layer, an AlGaAs emitter, and an ultra-thin AlGaAs window layer. The window layer is compositionally graded which minimizes reflection at the window layer/emitter interface and creates a built-in electric field to improve quantum response in the blue region of the spectrum. Liquid phase epitaxy (LPE) is the only viable method to produce this free standing top solar cell. Small (0.125 sq cm), transparent p/n AlGaAs top solar cells were demonstrated with optimum bandgap for combination with a silicon bottom solar cell. The efficiency of an AlGaAs/Si stack using the free standing AlGaAs device upon an existing silicon bottom solar cell is 24 pct. (1X, Air Mass Zero (AM0). The n/p AlGaAs top solar cell is being developed in order to facilitate the wiring configuration. The two terminal tandem stack will retain fit, form, and function of existing silicon solar cells. Progress in the development of large area (8 and 16 sq cm), free standing AlGaAs top solar cells is discussed

Suppression of prion protein in livestock by RNA interference

Given the difficulty of applying gene knockout technology to species other than mice, we decided to explore the utility of RNA interference (RNAi) in silencing the expression of genes in livestock. Short hairpin RNAs (shRNAs) were designed and screened for their ability to suppress the expression of caprine and bovine prion protein (PrP). Lentiviral vectors were used to deliver a transgene expressing GFP and an shRNA targeting PrP into goat fibroblasts. These cells were then used for nuclear transplantation to produce a cloned goat fetus, which was surgically recovered at 81 days of gestation and compared with an age-matched control derived by natural mating. All tissues examined in the cloned fetus expressed GFP, and PCR analysis confirmed the presence of the transgene encoding the PrP shRNA. Most relevant, Western blot analysis performed on brain tissues comparing the transgenic fetus with control demonstrated a significant (>90%) decrease in PrP expression levels. To confirm that similar methodologies could be applied to the bovine, recombinant virus was injected into the perivitelline space of bovine ova. After in vitro fertilization and culture, 76% of the blastocysts exhibited GFP expression, indicative that they expressed shRNAs targeting PrP. Our results provide strong evidence that the approach described here will be useful in producing transgenic livestock conferring potential disease resistance and provide an effective strategy for suppressing gene expression in a variety of large-animal models

Chemistry and structure by design: ordered CuNi(CN)4 sheets with copper(II) in a square-planar environment

Layered copper–nickel cyanide, CuNi(CN)4, a 2-D negative thermal expansion material, is one of a series of copper(II)-containing cyanides derived from Ni(CN)2. In CuNi(CN)4, unlike in Ni(CN)2, the cyanide groups are ordered generating square-planar Ni(CN)4 and Cu(NC)4 units. The adoption of square-planar geometry by Cu(II) in an extended solid is very unusual

A genome-wide RNAi screen identifies factors required for distinct stages of C-elegans piRNA biogenesis

In animals, piRNAs and their associated Piwi proteins guard germ cell genomes against mobile genetic elements via an RNAi-like mechanism. In Caenorhabditis elegans, 21U-RNAs comprise the piRNA class, and these collaborate with 22G RNAs via unclear mechanisms to discriminate self from nonself and selectively and heritably silence the latter. Recent work indicates that 21U-RNAs are post-transcriptional processing products of individual transcription units that produce similar to 26-nucleotide capped precursors. However, nothing is known of how the expression of precursors is controlled or how primary transcripts give rise to mature small RNAs. We conducted a genome-wide RNAi screen to identify components of the 21U biogenesis machinery. Screening by direct, quantitative PCR (qPCR)-based measurements of mature 21U-RNA levels, we identified 22 genes important for 21U-RNA production, termed TOFUs (Twenty-One-u Fouled Ups). We also identified seven genes that normally repress 21U production. By measuring mature 21U-RNA and precursor levels for the seven strongest hits from the screen, we assigned factors to discrete stages of 21U-RNA production. Our work identifies for the first time factors separately required for the transcription of 21U precursors and the processing of these precursors into mature 21U-RNAs, thereby providing a resource for studying the biogenesis of this important small RNA class

A machine learning case–control classifier for schizophrenia based on DNA methylation in blood

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants

Erratum to: Variation in 5-hydroxymethylcytosine across human cortex and cerebellum

This is the final version. Available from BMC via the DOI in this record.The article to which this is the erratum is in ORE at: http://hdl.handle.net/10871/2029

Cooperative effects in nuclear excitation with coherent x-ray light

The interaction between super-intense coherent x-ray light and nuclei is studied theoretically. One of the main difficulties with driving nuclear transitions arises from the very narrow nuclear excited state widths which limit the coupling between laser and nuclei. In the context of direct laser-nucleus interaction, we consider the nuclear width broadening that occurs when in solid targets, the excitation caused by a single photon is shared by a large number of nuclei, forming a collective excited state. Our results show that for certain isotopes, cooperative effects may lead to an enhancement of the nuclear excited state population by almost two orders of magnitude. Additionally, an update of previous estimates for nuclear excited state population and signal photons taking into account the experimental advances of the x-ray coherent light sources is given. The presented values are an improvement by orders of magnitude and are encouraging for the future prospects of nuclear quantum optics.Comment: 22 pages, 4 figures, 5 tables; updated to the published version, one additional results tabl

Methylomic trajectories across human fetal brain development

Open access articleEpigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity.MRCUniversity of Exeter Medical SchoolWellcome Trus