The Extraordinary Infrared Spectrum of NGC 1222 (Mkn 603)

The infrared spectra of starburst galaxies are dominated by the low-excitation lines of [NeII] and [SIII], and the stellar populations deduced from these spectra appear to lack stars larger than about 35 Msun. The only exceptions to this result until now were low metallicity dwarf galaxies. We report our analysis of the mid-infrared spectra obtained with IRS on Spitzer of the starburst galaxy NGC 1222 (Mkn 603). NGC 1222 is a large spheroidal galaxy with a starburst nucleus that is a compact radio and infrared source, and its infrared emission is dominated by the [NeIII] line. This is the first starburst of solar or near-solar metallicity, known to us, which is dominated by the high-excitation lines and which is a likely host of high mass stars. We model the emission with several different assumptions as to the spatial distibution of the high- and low-excitation lines and find that the upper mass cutoff in this galaxy is 40-100 Msun.Comment: accepted, Astronomical Journal. 29 pp, 4 figures. In replacement version an acknowledgment to NRAO is adde

Introduction to Arithmetic Mirror Symmetry

We describe how to find period integrals and Picard-Fuchs differential equations for certain one-parameter families of Calabi-Yau manifolds. These families can be seen as varieties over a finite field, in which case we show in an explicit example that the number of points of a generic element can be given in terms of p-adic period integrals. We also discuss several approaches to finding zeta functions of mirror manifolds and their factorizations. These notes are based on lectures given at the Fields Institute during the thematic program on Calabi-Yau Varieties: Arithmetic, Geometry, and Physics

Distribution of Eigenvalues for the Modular Group

The two-point correlation function of energy levels for free motion on the modular domain, both with periodic and Dirichlet boundary conditions, are explicitly computed using a generalization of the Hardy-Littlewood method. It is shown that ion the limit of small separations they show an uncorrelated behaviour and agree with the Poisson distribution but they have prominent number-theoretical oscillations at larger scale. The results agree well with numerical simulations.Comment: 72 pages, Latex, the fiogures mentioned in the text are not vital, but can be obtained upon request from the first Autho

Large format heterodyne arrays for observing far-infrared lines with SOFIA

In the wavelength regime between 60 and 300 microns there are a number of atomic and molecular emission lines that are key diagnostic probes of the interstellar medium. These include transitions of [CII], [NII], [OI], HD, H_2D^+, OH, CO, and H_2O, some of which are among the brightest global and local far-infrared lines in the Galaxy. In Giant Molecular Clouds (GMCs), evolved star envelopes, and planetary nebulae, these emission lines can be extended over many arc minutes and possess complicated, often self absorbed, line profiles. High spectral resolution (R > 10^5) observations of these lines at sub-arcminute angular resolution are crucial to understanding the complicated interplay between the interstellar medium and the stars that form from it. This feedback is central to all theories of galactic evolution. Large format heterodyne array receivers can provide the spectral resolution and spatial coverage to probe these lines over extended regions. The advent of large format (~100 pixel) spectroscopic imaging cameras in the far-infrared (FIR) will fundamentally change the way astronomy is performed in this important wavelength regime. While the possibility of such instruments has been discussed for more than two decades, only recently have advances in mixer and local oscillator technology, device fabrication, micromachining, and digital signal processing made the construction of such instruments tractable. These technologies can be implemented to construct a sensitive, flexible, heterodyne array facility instrument for SOFIA. The instrument concept for StratoSTAR: Stratospheric Submm/THz Array Receiver includes a common user mounting, control system, IF processor, spectrometer, and cryogenic system. The cryogenic system will be designed to accept a frontend insert. The frontend insert and associated local oscillator system/relay optics would be provided by individual user groups and reflect their scientific interests. Rapid technology development in this field makes SOFIA the ideal platform to operate such a modular, continuously evolving instrument

Joubert syndrome: genotyping a Northern European patient cohort

Joubert syndrome (JBS) is a rare neurodevelopmental disorder belonging to the group of ciliary diseases. JBS is genetically heterogeneous, with >20 causative genes identified to date. A molecular diagnosis of JBS is essential for prediction of disease progression and genetic counseling. We developed a targeted next-generation sequencing (NGS) approach for parallel sequencing of 22 known JBS genes plus 599 additional ciliary genes. This method was used to genotype a cohort of 51 well-phenotyped Northern European JBS cases (in some of the cases, Sanger sequencing of individual JBS genes had been performed previously). Altogether, 21 of the 51 cases (41%) harbored biallelic pathogenic mutations in known JBS genes, including 14 mutations not previously described. Mutations in C5orf42 (12%), TMEM67 (10%), and AHI1 (8%) were the most prevalent. C5orf42 mutations result in a purely neurological Joubert phenotype, in one case associated with postaxial polydactyly. Our study represents a population-based cohort of JBS patients not enriched for consanguinity, providing insight into the relative importance of the different JBS genes in a Northern European population. Mutations in C5orf42 are relatively frequent (possibly due to a Dutch founder mutation) and mutations in CEP290 are underrepresented compared with international cohorts. Furthermore, we report a case with heterozygous mutations in CC2D2A and B9D1, a gene associated with the more severe Meckel–Gruber syndrome that was recently published as a potential new JBS gene, and discuss the significance of this finding

Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0–2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84–2.45, P = 2.15 × 10−24) in the total cohort, 2.08 (1.72–2.50, P = 1.30 × 10−14) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37–2.99, P = 4.37 × 10−4) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence

Partner independent fusion gene detection by multiplexed CRISPR-Cas9 enrichment and long read nanopore sequencing

Fusion genes are hallmarks of various cancer types and important determinants for diagnosis, prognosis and treatment. Fusion gene partner choice and breakpoint-position promiscuity restricts diagnostic detection, even for known and recurrent configurations. Here, we develop FUDGE (FUsion Detection from Gene Enrichment) to accurately and impartially identify fusions. FUDGE couples target-selected and strand-specific CRISPR-Cas9 activity for fusion gene driver enrichment - without prior knowledge of fusion partner or breakpoint-location - to long read nanopore sequencing with the bioinformatics pipeline NanoFG. FUDGE has flexible target-loci choices and enables multiplexed enrichment for simultaneous analysis of several genes in multiple samples in one sequencing run. We observe on-average 665 fold breakpoint-site enrichment and identify nucleotide resolution fusion breakpoints within 2 days. The assay identifies cancer cell line and tumor sample fusions irrespective of partner gene or breakpoint-position. FUDGE is a rapid and versatile fusion detection assay for diagnostic pan-cancer fusion detection