Lentivector Transduction Improves Outcomes Over Transplantation of Human HSCs Alone in NOD/SCID/Fabry Mice

Fabry disease is a lysosomal storage disorder caused by a deficiency of a-galactosidase A (a-gal A) activity that results in progressive globotriaosylceramide (Gb(3)) deposition. We created a fully congenic nonobese diabetic (NOD)/severe combined immunodeficiency (SCID)/Fabry murine line to facilitate the in vivo assessment of human cell-directed therapies for Fabry disease. This pure line was generated after 11 generations of backcrosses and was found, as expected, to have a reduced immune compartment and background a-gal A activity. Next, we transplanted normal human CD34(+) cells transduced with a control (lentiviral vector-enhanced green fluorescent protein (LV-eGFP)) or a therapeutic bicistronic LV (LV-a-gal A/internal ribosome entry site (IRES)/hCD25). While both experimental groups showed similar engraftment levels, only the therapeutic group displayed a significant increase in plasma a-gal A activity. Gb(3) quantification at 12 weeks revealed metabolic correction in the spleen, lung, and liver for both groups. Importantly, only in the therapeutically-transduced cohort was a significant Gb(3) reduction found in the heart and kidney, key target organs for the amelioration of Fabry disease in humans.Fil: Pacienza, Natalia Alejandra. University Health Network; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Yoshimitsu, Makoto. Kagoshima University; Japón. University Health Network; CanadáFil: Mizue, Nobuo. University Health Network; CanadáFil: Au, Bryan C. Y.. University Health Network; CanadáFil: Wang, James C. M.. University Health Network; CanadáFil: Fan, Xin. University Health Network; CanadáFil: Takenaka, Toshihiro. Kagoshima University; JapónFil: Medin, Jeffrey A. University Health Network; Canadá. University of Toronto; Canad

Terahertz metamaterials on free-standing highly-flexible polyimide substrates

We have fabricated resonant terahertz metamaterials on free standing polyimide substrates. The low-loss polyimide substrates can be as thin as 5.5 micron yielding robust large-area metamaterials which are easily wrapped into cylinders with a radius of a few millimeters. Our results provide a path forward for creating multi-layer non-planar metamaterials at terahertz frequencies.Comment: 4 pages, higher resolution figures available upon reques

Nonlinear terahertz metamaterials via field-enhanced carrier dynamics in GaAs

We demonstrate nonlinear metamaterial split ring resonators (SRRs) on GaAs at terahertz frequencies. For SRRs on doped GaAs films, incident terahertz radiation with peak fields of ~20 - 160 kV/cm drives intervalley scattering. This reduces the carrier mobility and enhances the SRR LC response due to a conductivity decrease in the doped thin film. Above ~160 kV/cm, electric field enhancement within the SRR gaps leads to efficient impact ionization, increasing the carrier density and the conductivity which, in turn, suppresses the SRR resonance. We demonstrate an increase of up to 10 orders of magnitude in the carrier density in the SRR gaps on semi-insulating GaAs substrate. Furthermore, we show that the effective permittivity can be swept from negative to positive values with increasing terahertz field strength in the impact ionization regime, enabling new possibilities for nonlinear metamaterials.Comment: 5 pages, 4 figure

Geochronological, elemental and Sr-Nd-Hf-O isotopic constraints on the petrogenesis of the Triassic post-collisional granitic rocks in NW Thailand and its Paleotethyan implications

This study was jointly funded by the National Science Foundation of China (41190073), National Basic Research Program of China (2014CB440901 and 2016YFC0600303) and the Fundamental Research Funds for the Central Universities to SYSU.New U-Pb geochronological, petrologic, elemental and Sr-Nd-Hf-O isotopic data for the granites from the Inthanon and Sukhothai zones in NW Thailand in conjunction with correlations with SW China are presented to constrain the age and position of the Paleotethys Ocean in this region and the associated assembly of Southeast Asia. The geochronological data show that the granitic rocks in the Inthanon and Sukhothai zones, herein named Group 1 and Group 2 granites, respectively, yield similar crystallization ages of 230-200 Ma. Group 1 samples are characterized by monzogranite and granite with I- and S-type geochemical affinity and Group 2 samples by I-type monzogranite and granodiorite. They have generally similar chondrite-normalized REE and PM- normalized multi-element patterns but distinct Sr-Nd-Hf-O isotopic compositions. Group 1 samples have slightly higher initial 87Sr/86Sr ratios (0.7111- 0.7293) but lower εNd(t) values (-11.1 ~ -14.1) than those of Group 2 samples (87Sr/86Sr(i)=0.7073-0.7278 and εNd(t)=-8.3 ~ -11.0). Group 1 samples show the lower εHf(t) values (-5.4 ~ -18.2), older TDM (1.62-2.40 Ga) and higher δ18O values (+ 7.95-+9.94) than those of Group 2 samples (εHf(t) of -11.1-+4.80, TDM of 0.96-1.95 Ga and δ18O of + 4.95 ~+7.98) for the Triassic crystallization zircons. These geochemical signatures are similar to the Kwangsian and Indosinian granites in the South China and Indochina blocks but distinct from those of the Gangdese I-type granite and Sibumasu Paleozoic granite. Our data suggest that Group 1 samples mainly originated from the early Paleozoic supracrustal rocks containing metapelite and metavolcanic components, which had previously experienced the surface weathering. Group 2 samples were derived from a hybridized source of an old metamorphic and a newly underplated mafic component. Synthesis of our data with available regional observations indicate that the Inthanon zone represents the main suture zone of the eastern Paleotethyan Ocean in NW Thailand and links with the Changning-Menglian suture zone in SW Yunnan (SW China). In NW Thailand, a switch from the eastward subduction of the Paleotethyan oceanic plate to the collision of the Sibumasu with Indochina blocks occurred at ~ 237 Ma, and syn- and post-collisional time being at ~ 237-230 Ma and ~ 200-230 Ma, respectively. The late Triassic granites in the Inthanon and Sukhothai zones are representative of the post-collisional magmatic products.PostprintPeer reviewe

The SDSS-IV extended Baryon Oscillation Spectroscopic Survey: selecting emission line galaxies using the Fisher discriminant

We present a new selection technique of producing spectroscopic target catalogues for massive spectroscopic surveys for cosmology. This work was conducted in the context of the extended Baryon Oscillation Spectroscopic Survey (eBOSS), which will use ~200 000 emission line galaxies (ELGs) at 0.6<zspec<1.0 to obtain a precise baryon acoustic oscillation measurement. Our proposed selection technique is based on optical and near-infrared broad-band filter photometry. We used a training sample to define a quantity, the Fisher discriminant (linear combination of colours), which correlates best with the desired properties of the target: redshift and [OII] flux. The proposed selections are simply done by applying a cut on magnitudes and this Fisher discriminant. We used public data and dedicated SDSS spectroscopy to quantify the redshift distribution and [OII] flux of our ELG target selections. We demonstrate that two of our selections fulfil the initial eBOSS/ELG redshift requirements: for a target density of 180 deg^2, ~70% of the selected objects have 0.6<zspec<1.0 and only ~1% of those galaxies in the range 0.6<zspec<1.0 are expected to have a catastrophic zspec estimate. Additionally, the stacked spectra and stacked deep images for those two selections show characteristic features of star-forming galaxies. The proposed approach using the Fisher discriminant could, however, be used to efficiently select other galaxy populations, based on multi-band photometry, providing that spectroscopic information is available. This technique could thus be useful for other future massive spectroscopic surveys such as PFS, DESI, and 4MOST.Comment: Version published in A&