Stellar and Molecular Radii of a Mira Star: First Observations with the Keck Interferometer Grism

Using a new grism at the Keck Interferometer, we obtained spectrally dispersed (R ~ 230) interferometric measurements of the Mira star R Vir. These data show that the measured radius of the emission varies substantially from 2.0-2.4 microns. Simple models can reproduce these wavelength-dependent variations using extended molecular layers, which absorb stellar radiation and re-emit it at longer wavelengths. Because we observe spectral regions with and without substantial molecular opacity, we determine the stellar photospheric radius, uncontaminated by molecular emission. We infer that most of the molecular opacity arises at approximately twice the radius of the stellar photosphere.Comment: 12 pages, including 3 figures. Accepted by ApJ

Rates of asymptomatic respiratory virus infection across age groups.

Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population

Keck Interferometer Nuller Data Reduction and On-Sky Performance

We describe the Keck Interferometer nuller theory of operation, data reduction, and on-sky performance, particularly as it applies to the nuller exozodiacal dust key science program that was carried out between 2008 February and 2009 January. We review the nuller implementation, including the detailed phasor processing involved in implementing the null-peak mode used for science data and the sequencing used for science observing. We then describe the Level 1 reduction to convert the instrument telemetry streams to raw null leakages, and the Level 2 reduction to provide calibrated null leakages. The Level 1 reduction uses conservative, primarily linear processing, implemented consistently for science and calibrator stars. The Level 2 processing is more flexible, and uses diameters for the calibrator stars measured contemporaneously with the interferometer’s K-band cophasing system in order to provide the requisite accuracy. Using the key science data set of 462 total scans, we assess the instrument performance for sensitivity and systematic error. At 2.0 Jy we achieve a photometrically-limited null leakage uncertainty of 0.25% rms per 10 minutes of integration time in our broadband channel. From analysis of the Level 2 reductions, we estimate a systematic noise floor for bright stars of ~0.2% rms null leakage uncertainty per observing cluster in the broadband channel. A similar analysis is performed for the narrowband channels. We also provide additional information needed for science reduction, including details on the instrument beam pattern and the basic astrophysical response of the system, and references to the data reduction and modeling tools

The dusty AGB star RS CrB: first mid-infrared interferometric observations with the Keck Telescopes

We report interferometric observations of the semi-regular variable star RS CrB, a red giant with strong silicate emission features. The data were among the first long baseline mid-infrared stellar fringes obtained between the Keck telescopes, using parts of the new nulling beam combiner. The light was dispersed by a low-resolution spectrometer, allowing simultaneous measurement of the source visibility and intensity spectra from 8 to 12 microns. The interferometric observations allow a non-ambiguous determination of the dust shell spatial scale and relative flux contribution. Using a simple spherically-symmetric model, in which a geometrically thin shell surrounds the stellar photosphere, we find that ~30% to ~70% of the overall mid-infrared flux - depending on the wavelength - originates from 7-8 stellar radii. The derived shell opacity profile shows a broad peak around 11 microns (tau ~ 0.06), characteristic of Mg-rich silicate dust particles.Comment: Accepted for publication in ApJ Letter

The near-infrared size-luminosity relations for Herbig Ae/Be disks

We report the results of a sensitive K-band survey of Herbig Ae/Be disk sizes using the 85-m baseline Keck Interferometer. Targets were chosen to span the maximum range of stellar properties to probe the disk size dependence on luminosity and effective temperature. For most targets, the measured near-infrared sizes (ranging from 0.2 to 4 AU) support a simple disk model possessing a central optically-thin (dust-free) cavity, ringed by hot dust emitting at the expected sublimation temperatures (T_sub~1000-1500K). Furthermore, we find a tight correlation of disk size with source luminosity R propto L^(1/2) for Ae and late Be systems (valid over more than 2 decades in luminosity), confirming earlier suggestions based on lower-quality data. Interestingly, the inferred dust-free inner cavities of the highest luminosity sources (Herbig B0-B3 stars) are under-sized compared to predictions of the optically-thin cavity model, likely due to optically-thick gas within the inner AU.Comment: Accepted by Astrophysical Journal; 24 pages, 4 figures, 4 table

Milliarcsecond N-Band Observations of the Nova RS Ophiuchi: First Science with the Keck Interferometer Nuller

We report observations of the nova RS Ophiuchi (RS Oph) using the Keck Interferometer Nuller (KIN), approximately 3.8 days following the most recent outburst that occurred on 2006 February 12. These observations represent the first scientific results from the KIN, which operates in N-band from 8 to 12.5 microns in a nulling mode. By fitting the unique KIN data, we have obtained an angular size of the mid-infrared continuum of 6.2, 4.0, or 5.4 mas for a disk profile, gaussian profile (FWHM), and shell profile respectively. The data show evidence of enhanced neutral atomic hydrogen emission and atomic metals including silicon located in the inner spatial regime near the white dwarf (WD) relative to the outer regime. There are also nebular emission lines and evidence of hot silicate dust in the outer spatial region, centered at ! 17 AU from the WD, that are not found in the inner regime. Our evidence suggests that these features have been excited by the nova flash in the outer spatial regime before the blast wave reached these regions. These identifications support a model in which the dust appears to be present between outbursts and is not created during the outburst event. We further discuss the present results in terms of a unifying model of the system that includes an increase in density in the plane of the orbit of the two stars created by a spiral shock wave caused by the motion of the stars through the cool wind of the red giant star. These data show the power and potential of the nulling technique which has been developed for the detection of Earth-like planets around nearby stars for the Terrestrial Planet Finder Mission and Darwin missions.Comment: 41 pages, 10 figure

Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer

BACKGROUND: Circulating tumour cells (CTCs) offer a non-invasive approach to obtain and characterise metastatic tumour cells, but their usefulness has been limited by low CTC yields from conventional isolation methods. METHODS: To improve CTC yields and facilitate their molecular characterisation we compared the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK) to a simplified CTC capture method, CellSearch Profile Kit (CPK), on paired blood samples from patients with metastatic breast (n=75) and lung (n=71) cancer. Molecular markers including Human Epidermal growth factor Receptor 2 (HER2) were evaluated on CTCs by fluorescence in situ hybridisation (FISH) and compared to patients' primary and metastatic cancer. RESULTS: The median cell count from patients with breast cancer using the CPK was 117 vs 4 for CEK (P<0.0001). Lung cancer samples were similar; CPK: 145 cells vs CEK:4 cells (P<0.0001). Recovered CTCs were relatively pure (60-70%) and were evaluable by FISH and immunofluorescence. A total of 10 of 30 (33%) breast cancer patients with HER2-negative primary and metastatic tissue had HER2-amplified CTCs. CONCLUSION: The CPK method provides a high yield of relatively pure CTCs, facilitating their molecular characterisation. Circulating tumour cells obtained using CPK technology demonstrate that significant discordance exists between HER2 amplification of a patient's CTCs and that of the primary and metastatic tumour

Keck Interferometer Observations of FU Orionis Objects

We present new K-band long baseline interferometer observations of three young stellar objects of the FU Orionis class, V1057 Cyg, V1515 Cyg and Z CMa-SE, obtained at the Keck Interferometer during its commissioning science period. The interferometer clearly resolves the source of near-infrared emission in all three objects. Using simple geometrical models we derive size scales (0.5-4.5 AU) for this emission. All three objects appear significantly more resolved than expected from simple models of accretion disks tuned to fit the broadband optical and infrared spectro-photometry. We explore variations in the key parameters that are able to lower the predicted visibility amplitudes to the measured levels, and conclude that accretion disks alone do not reproduce the spectral energy distributions and K-band visibilities simultaneously. We conclude that either disk models are inadequate to describe the near-infrared emission, or additional source components are needed. We hypothesize that large scale emission (10s of AU) in the interferometer field of view is responsible for the surprisingly low visibilities. This emission may arise in scattering by large envelopes believed to surround these objects.Comment: Accepted by The Astrophysical Journal, in pres

Subependymal giant cell astrocytomas are characterized by mTORC1 hyperactivation, a very low somatic mutation rate, and a unique gene expression profile

Subependymal giant-cell astrocytomas (SEGAs) are slow-growing brain tumors that are a hallmark feature seen in 5–10% of patients with Tuberous Sclerosis Complex (TSC). Though histologically benign, they can cause serious neurologic symptoms, leading to death if untreated. SEGAs consistently show biallelic loss of TSC1 or TSC2. Herein, we aimed to define other somatic events beyond TSC1/TSC2 loss and identify potential transcriptional drivers that contribute to SEGA formation. Paired tumor-normal whole-exome sequencing was performed on 21 resected SEGAs from 20 TSC patients. Pathogenic variants in TSC1/TSC2 were identified in 19/21 (90%) SEGAs. Copy neutral loss of heterozygosity (size range: 2.2–46 Mb) was seen in 76% (16/21) of SEGAs (44% chr9q and 56% chr16p). An average of 1.4 other somatic variants (range 0–7) per tumor were identified, unlikely of pathogenic significance. Whole transcriptome RNA-sequencing analyses revealed 190 common differentially expressed genes in SEGA (n = 16, 13 from a prior study) in pairwise comparison to each of: low grade diffuse gliomas (n = 530) and glioblastoma (n = 171) from The Cancer Genome Atlas (TCGA) consortium, ganglioglioma (n = 10), TSC cortical tubers (n = 15), and multiple normal tissues. Among these, homeobox transcription factors (TFs) HMX3, HMX2, VAX1, SIX3; and TFs IRF6 and EOMES were all expressed >12-fold higher in SEGAs (FDR/q-value < 0.05). Immunohistochemistry supported the specificity of IRF6, VAX1, SIX3 for SEGAs in comparison to other tumor entities and normal brain. We conclude that SEGAs have an extremely low somatic mutation rate, suggesting that TSC1/TSC2 loss is sufficient to drive tumor growth. The unique and highly expressed SEGA-specific TFs likely reflect the neuroepithelial cell of origin, and may also contribute to the transcriptional and epigenetic state that enables SEGA growth following two-hit loss of TSC1 or TSC2 and mTORC1 activation