Nano-optical single-photon response mapping of waveguide integrated molybdenum silicide (MoSi) superconducting nanowires.

We present low temperature nano-optical characterization of a silicon-on-insulator (SOI) waveguide integrated SNSPD. The SNSPD is fabricated from an amorphous Mo83Si17 thin film chosen to give excellent substrate conformity. At 350 mK, the SNSPD exhibits a uniform photoresponse under perpendicular illumination, corresponding to a maximum system detection efficiency of approximately 5% at 1550 nm wavelength. Under these conditions 10 Hz dark count rate and 51 ps full width at half maximum (FWHM) timing jitter is observed.

Decoding cell lineage from acquired mutations using arbitrary deep sequencing.

Because mutations are inevitable, the genome of each cell in a multicellular organism becomes unique and therefore encodes a record of its ancestry. Here we coupled arbitrary single primer PCR with next-generation DNA sequencing to catalog mutations and deconvolve the phylogeny of cultured mouse cells. This study helps pave the way toward construction of retrospective cell-fate maps based on mutations accumulating in genomes of somatic cells.

Superconducting nanowire single-photon detectors with non-periodic dielectric multilayers.

We present superconducting nanowire single-photon detectors (SSPDs) on non-periodic dielectric multilayers, which enable us to design a variety of wavelength dependences of optical absorptance by optimizing the dielectric multilayer. By adopting a robust simulation to optimize the dielectric multilayer, we designed three types of SSPDs with target wavelengths of 500 nm, 800 nm, and telecom range respectively. We fabricated SSPDs based on the optimized designs for 500 and 800 nm, and evaluated the system detection efficiency at various wavelengths. The results obtained confirm that the designed SSPDs with non-periodic dielectric multilayers worked well. This versatile device structure can be effective for multidisciplinary applications in fields such as the life sciences and remote sensing that require high efficiency over a precise spectral range and strong signal rejection at other wavelengths.

Copper-free click chemistry as an emerging tool for the programmed ligation of DNA-functionalised gold nanoparticles.

We demonstrate a new method to program the ligation of single stranded DNA-modified gold nanoparticles using copper-free click chemistry. Gold nanoparticles functionalized with a discrete number of 3'-azide or 5'-alkyne modified oligonucleotides, can be brought together via a splint strand and covalently 'clicked', in a simple one-pot reaction. This new approach to the assembly of gold nanoparticles is inherently advantageous in comparison to the traditional enzymatic ligation. The chemical ligation is specific and takes place at room temperature by simply mixing the particles without the need for special enzymatic conditions. The yield of 'clicked' nanoparticles can be as high as 92%. The ease of the copper-free, 'click-ligation' method allows for its universal applicability and opens up new avenues in programmed nanoparticle organization.

Support for the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families.

IMPORTANCE: Schizophrenia is a complex genetic disorder demonstrating considerable heritability. Genetic studies have implicated many different genes and pathways, but much of the genetic liability remains unaccounted for. Investigation of genetic forms of schizophrenia will lead to a better understanding of the underlying molecular pathways, which will then enable targeted approaches for disease prevention and treatment. OBJECTIVE: To identify new genetic factors strongly predisposing to schizophrenia in families with multiple affected individuals with schizophrenia. DESIGN: We performed genome-wide array comparative genomic hybridization, linkage analysis, and exome sequencing in multiplex families with schizophrenia. SETTING: Probands and their family members were recruited from academic medical centers. PARTICIPANTS: We intended to identify rare disease-causing mutations in 5 large families where schizophrenia transmission appears consistent with single-gene inheritance. INTERVENTION: Array comparative genomic hybridization was used to identify copy number variants, while exome sequencing was used to identify variants shared in all affected individuals and linkage analysis was used to further filter shared variants of interest. Analysis of select variants was performed in cultured cells to assess their functional consequences. MAIN OUTCOME MEASURES: Rare inherited disease-related genetic mutations. RESULTS: No segregating rare copy number variants were detected by array comparative genomic hybridization. However, in all 5 families, exome sequencing detected rare protein-altering variants in 1 of 3 genes associated with the N -methyl-D-aspartate (NMDA) receptor. One pedigree shared a missense and frameshift substitution of GRM5, encoding the metabotropic glutamate receptor subtype 5 (mGluR5), which is coupled to the NMDA receptor and potentiates its signaling; the frameshift disrupts binding to the scaffolding protein tamalin and increases mGluR5 internalization. Another pedigree transmitted a missense substitution in PPEF2, encoding a calmodulin-binding protein phosphatase, which we show influences mGluR5 levels. Three pedigrees demonstrated different missense substitutions within LRP1B, encoding a low-density lipoprotein receptor-related protein tied to both the NMDA receptor and located in a chromosome 2q22 region previously strongly linked to schizophrenia. CONCLUSIONS AND RELEVANCE: Exome sequencing of multiplex pedigrees uncovers new genes associated with risk for developing schizophrenia and suggests potential novel therapeutic targets.