Exploring the spectral diversity of low-redshift Type Ia supernovae using the Palomar Transient Factory

We present an investigation of the optical spectra of 264 low-redshift (z < 0.2) Type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory, an untargeted transient survey. We focus on velocity and pseudo-equivalent width measurements of the Si II 4130, 5972, and 6355 A lines, as well those of the Ca II near-infrared (NIR) triplet, up to +5 days relative to the SN B-band maximum light. We find that a high-velocity component of the Ca II NIR triplet is needed to explain the spectrum in ~95 per cent of SNe Ia observed before -5 days, decreasing to ~80 per cent at maximum. The average velocity of the Ca II high-velocity component is ~8500 km/s higher than the photospheric component. We confirm previous results that SNe Ia around maximum light with a larger contribution from the high-velocity component relative to the photospheric component in their Ca II NIR feature have, on average, broader light curves and lower Ca II NIR photospheric velocities. We find that these relations are driven by both a stronger high-velocity component and a weaker contribution from the photospheric Ca II NIR component in broader light curve SNe Ia. We identify the presence of C II in very-early-time SN Ia spectra (before -10 days), finding that >40 per cent of SNe Ia observed at these phases show signs of unburnt material in their spectra, and that C II features are more likely to be found in SNe Ia having narrower light curves.Comment: 18 page, 10 figures, accepted for publication in MNRA

Decentralizing Inner-Product Functional Encryption

International audienceMulti-client functional encryption (MCFE) is a more flexible variant of functional encryption whose functional decryption involves multiple ciphertexts from different parties. Each party holds a different secret key and can independently and adaptively be corrupted by the adversary. We present two compilers for MCFE schemes for the inner-product functionality, both of which support encryption labels. Our first compiler transforms any scheme with a special key-derivation property into a decentralized scheme, as defined by Chotard et al. (ASIACRYPT 2018), thus allowing for a simple distributed way of generating functional decryption keys without a trusted party. Our second compiler allows to lift an unnatural restriction present in existing (decentralized) MCFE schemes, which requires the adversary to ask for a ciphertext from each party. We apply our compilers to the works of Abdalla et al. (CRYPTO 2018) and Chotard et al. (ASIACRYPT 2018) to obtain schemes with hitherto unachieved properties. From Abdalla et al., we obtain instantiations of DMCFE schemes in the standard model (from DDH, Paillier, or LWE) but without labels. From Chotard et al., we obtain a DMCFE scheme with labels still in the random oracle model, but without pairings

SNLS3: Constraints on Dark Energy Combining the Supernova Legacy Survey Three Year Data with Other Probes

We present observational constraints on the nature of dark energy using the Supernova Legacy Survey three year sample (SNLS3) of Guy et al. (2010) and Conley et al. (2011). We use the 472 SNe Ia in this sample, accounting for recently discovered correlations between SN Ia luminosity and host galaxy properties, and include the effects of all identified systematic uncertainties directly in the cosmological fits. Combining the SNLS3 data with the full WMAP7 power spectrum, the Sloan Digital Sky Survey luminous red galaxy power spectrum, and a prior on the Hubble constant H0 from SHOES, in a flat universe we find omega_m=0.269+/-0.015 and w=-1.061+0.069-0.068 -- a 6.5% measure of the dark energy equation-of-state parameter w. The statistical and systematic uncertainties are approximately equal, with the systematic uncertainties dominated by the photometric calibration of the SN Ia fluxes -- without these calibration effects, systematics contribute only a ~2% error in w. When relaxing the assumption of flatness, we find omega_m=0.271+/-0.015, omega_k=-0.002+/-0.006, and w=-1.069+0.091-0.092. Parameterizing the time evolution of w as w(a)=w_0+w_a(1-a), gives w_0=-0.905+/-0.196, w_a=-0.984+1.094-1.097 in a flat universe. All of our results are consistent with a flat, w=-1 universe. The size of the SNLS3 sample allows various tests to be performed with the SNe segregated according to their light curve and host galaxy properties. We find that the cosmological constraints derived from these different sub-samples are consistent. There is evidence that the coefficient, beta, relating SN Ia luminosity and color, varies with host parameters at >4sigma significance (in addition to the known SN luminosity--host relation); however this has only a small effect on the cosmological results and is currently a sub-dominant systematic.Comment: Accepted for publication in ApJ. Data available from https://tspace.library.utoronto.ca/snl

bantam Is Required for Optic Lobe Development and Glial Cell Proliferation

microRNAs (miRNAs) are small, conserved, non-coding RNAs that contribute to the control of many different cellular processes, including cell fate specification and growth control. Drosophila bantam, a conserved miRNA, is involved in several functions, such as stimulating proliferation and inhibiting apoptosis in the wing disc. Here, we reported the detailed expression pattern of bantam in the developing optic lobe, and demonstrated a new, essential role in promoting proliferation of mitotic cells in the optic lobe, including stem cells and differentiated glial cells. Changes in bantam levels autonomously affected glial cell number and distribution, and non-autonomously affected photoreceptor neuron axon projection patterns. Furthermore, we showed that bantam promotes the proliferation of mitotically active glial cells and affects their distribution, largely through down regulation of the T-box transcription factor, optomotor-blind (omb, Flybase, bifid). Expression of omb can rescue the bantam phenotype, and restore the normal glial cell number and proper glial cell positioning in most Drosophila brains. These results suggest that bantam is critical for maintaining the stem cell pools in the outer proliferation center and glial precursor cell regions of the optic lobe, and that its expression in glial cells is crucial for their proliferation and distribution

Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus Infection

BACKGROUND: Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc. METHODS: We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals. RESULTS: In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011). CONCLUSION: This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination

A Drosophila Model for EGFR-Ras and PI3K-Dependent Human Glioma

Gliomas, the most common malignant tumors of the nervous system, frequently harbor mutations that activate the epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling pathways. To investigate the genetic basis of this disease, we developed a glioma model in Drosophila. We found that constitutive coactivation of EGFR-Ras and PI3K pathways in Drosophila glia and glial precursors gives rise to neoplastic, invasive glial cells that create transplantable tumor-like growths, mimicking human glioma. Our model represents a robust organotypic and cell-type-specific Drosophila cancer model in which malignant cells are created by mutations in signature genes and pathways thought to be driving forces in a homologous human cancer. Genetic analyses demonstrated that EGFR and PI3K initiate malignant neoplastic transformation via a combinatorial genetic network composed primarily of other pathways commonly mutated or activated in human glioma, including the Tor, Myc, G1 Cyclins-Cdks, and Rb-E2F pathways. This network acts synergistically to coordinately stimulate cell cycle entry and progression, protein translation, and inappropriate cellular growth and migration. In particular, we found that the fly orthologs of CyclinE, Cdc25, and Myc are key rate-limiting genes required for glial neoplasia. Moreover, orthologs of Sin1, Rictor, and Cdk4 are genes required only for abnormal neoplastic glial proliferation but not for glial development. These and other genes within this network may represent important therapeutic targets in human glioma

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

Systematic Identification of Genes that Regulate Neuronal Wiring in the Drosophila Visual System

Forward genetic screens in model organisms are an attractive means to identify those genes involved in any complex biological process, including neural circuit assembly. Although mutagenesis screens are readily performed to saturation, gene identification rarely is, being limited by the considerable effort generally required for positional cloning. Here, we apply a systematic positional cloning strategy to identify many of the genes required for neuronal wiring in the Drosophila visual system. From a large-scale forward genetic screen selecting for visual system wiring defects with a normal retinal pattern, we recovered 122 mutations in 42 genetic loci. For 6 of these loci, the underlying genetic lesions were previously identified using traditional methods. Using SNP-based mapping approaches, we have now identified 30 additional genes. Neuronal phenotypes have not previously been reported for 20 of these genes, and no mutant phenotype has been previously described for 5 genes. The genes encode a variety of proteins implicated in cellular processes such as gene regulation, cytoskeletal dynamics, axonal transport, and cell signalling. We conducted a comprehensive phenotypic analysis of 35 genes, scoring wiring defects according to 33 criteria. This work demonstrates the feasibility of combining large-scale gene identification with large-scale mutagenesis in Drosophila, and provides a comprehensive overview of the molecular mechanisms that regulate visual system wiring

Computational Characterization of 3′ Splice Variants in the GFAP Isoform Family

Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate cellular structure, but also cellular function. Moreover, GFAP has a family of splicing isoforms apparently more complex than that of other CNS IF proteins, consistent with it possessing a range of functional and structural roles. The gene consists of 9 exons, and to date all isoforms associated with 3′ end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPδ/ε) and 7b (GFAPκ). To better understand the nature and functional significance of variation in this region, we used a Bayesian multiple change-point approach to identify conserved regions. This is the first successful application of this method to a single gene – it has previously only been used in whole-genome analyses. We identified several highly or moderately conserved regions throughout the intron 7/7a/7b regions, including untranslated regions and regulatory features, consistent with the biology of GFAP. Several putative unconfirmed features were also identified, including a possible new isoform. We then integrated multiple computational analyses on both the DNA and protein sequences from the mouse, rat and human, showing that the major isoform, GFAPα, has highly conserved structure and features across the three species, whereas the minor isoforms GFAPδ/ε and GFAPκ have low conservation of structure and features at the distal 3′ end, both relative to each other and relative to GFAPα. The overall picture suggests distinct and tightly regulated functions for the 3′ end isoforms, consistent with complex astrocyte biology. The results illustrate a computational approach for characterising splicing isoform families, using both DNA and protein sequences