Development of a unique laboratory standard indium gallium arsenide detector for the 500 to 1700 micron spectral region, phase 2

In the course of this work, 5 mm diameter InGaAs pin detectors were produced which met or exceeded all of the goals of the program. The best results achieved were: shunt resistance of over 300 K ohms; rise time of less than 300 ns; contact resistance of less than 20 ohms; quantum efficiency of over 50 percent in the 0.5 to 1.7 micron range; and devices were maintained and operated at 125 C without deterioration for over 100 hours. In order to achieve the goals of this program, several major technological advances were realized, among them: successful design, construction and operation of a hydride VPE reactor capable of growing epitaxial layers on 2 inch diameter InP substrates with a capacity of over 8 wafers per day; wafer processing was upgraded to handle 2 inch wafers; a double layer Si3N4/SiO2 antireflection coating which enhances response over the 0.5 to 1.7 micron range was developed; a method for anisotropic, precisely controlled CH4/H2 plasma etching for enhancement of response at short wavelengths was developed; and electronic and optical testing methods were developed to allow full characterization of detectors with size and spectral response characteristics. On the basis of the work and results achieved in this program, it is concluded that large size, high shunt resistance, high quantum efficiency InGaAs pin detectors are not only feasible but also manufacturable on industrial scale. This device spans a significant portion of visible and near infrared spectral range and it will allow a single detector to be used for the 0.5 to 1.7 micron spectral region, rather than the presently used silicon (for 0.5 to 1.1 microns) and germanium (0.8 to 1.7 microns)

Method of fabricating multiwavelength infrared focal plane array detector

A multiwavelength local plane array infrared detector is included on a common substrate having formed on its top face a plurality of In.sub.x Ga.sub.1-x As (x.ltoreq.0.53) absorption layers, between each pair of which a plurality of InAs.sub.y P.sub.1-y (y.ltoreq.1) buffer layers are formed having substantially increasing lattice parameters, respectively, relative to said substrate, for preventing lattice mismatch dislocations from propagating through successive ones of the absorption layers of decreasing bandgap relative to said substrate, whereby a plurality of detectors for detecting different wavelengths of light for a given pixel are provided by removing material above given areas of successive ones of the absorption layers, which areas are doped to form a pn junction with the surrounding unexposed portions of associated absorption layers, respectively, with metal contacts being formed on a portion of each of the exposed areas, and on the bottom of the substrate for facilitating electrical connections thereto

Reliability and validity of neurobehavioral function on the Psychology Experimental Building Language test battery in young adults

Background. The Psychology Experiment Building Language (PEBL) software consists of over one-hundred computerized tests based on classic and novel cognitive neuropsychology and behavioral neurology measures. Although the PEBL tests are becoming more widely utilized, there is currently very limited information about the psychometric properties of these measures. Methods. Study I examined inter-relationships among nine PEBL tests including indices of motor-function (Pursuit Rotor and Dexterity), attention (Test of Attentional Vigilance and Time-Wall), working memory (Digit Span Forward), and executive-function (PEBL Trail Making Test, Berg/Wisconsin Card Sorting Test, Iowa Gambling Test, and Mental Rotation) in a normative sample (N = 189, ages 18–22). Study II evaluated test–retest reliability with a two-week interest interval between administrations in a separate sample (N = 79, ages 18–22). Results. Moderate intra-test, but low inter-test, correlations were observed and ceiling/floor effects were uncommon. Sex differences were identified on the Pursuit Rotor (Cohen’s d = 0.89) and Mental Rotation (d = 0.31) tests. The correlation between the test and retest was high for tests of motor learning (Pursuit Rotor time on target r = .86) and attention (Test of Attentional Vigilance response time r = .79), intermediate for memory (digit span r = .63) but lower for the executive function indices (Wisconsin/Berg Card Sorting Test perseverative errors = .45, Tower of London moves = .15). Significant practice effects were identified on several indices of executive function. Conclusions. These results are broadly supportive of the reliability and validity of individual PEBL tests in this sample. These findings indicate that the freely downloadable, open-source PEBL battery (http://pebl.sourceforge.net) is a versatile research tool to study individual differences in neurocognitive performance

An Improved uvby-Metallicity Calibration for Metal-Rich Stars

We present an improved uvby-metallicity relation calibrated for F, G, and early K dwarfs, and an analogous uvby-T(eff) relation, both derived using a Levenberg-Marquardt minimization scheme. Our calibrations are based on 1533 stars which appear in both the Cayrel de Strobel (2001) metallicity compilation, and in the Hauck-Mermilliod (1998) catalog of uvby photometry. We also examine the speculative possibility of using uvby photometry to produce a uvby-planeticity calibration. We conclude that while there is likely no strong photometric indicator of the presence or absence of short-period planets, the possibility of a spectroscopic indicator of planeticity is well worth examining.Comment: 9 pages, 4 figures, accepted in ApJ Letter

Corticosteroids increase the risk of invasive fungal infections more than tumor necrosis factor-alpha inhibitors in patients with inflammatory bowel disease

BACKGROUND: Invasive fungal infections are a devastating complication of inflammatory bowel disease (IBD) treatment. We aimed to determine the incidence of fungal infections in IBD patients and examine the risk with tumor necrosis factor-alpha inhibitors (anti-TNF) compared with corticosteroids. METHODS: In a retrospective cohort study using the IBM MarketScan Commercial Database we identified US patients with IBD and at least 6 months enrollment from 2006 to 2018. The primary outcome was a composite of invasive fungal infections, identified by ICD-9/10-CM codes plus antifungal treatment. Tuberculosis (TB) infections were a secondary outcome, with infections presented as cases/100 000 person-years (PY). A proportional hazards model was used to determine the association of IBD medications (as time-dependent variables) and invasive fungal infections, controlling for comorbidities and IBD severity. RESULTS: Among 652 920 patients with IBD, the rate of invasive fungal infections was 47.9 cases per 100 000 PY (95% CI 44.7-51.4), which was more than double the TB rate (22 cases [CI 20-24], per 100 000 PY). Histoplasmosis was the most common invasive fungal infection (12.0 cases [CI 10.4-13.8] per 100 000 PY). After controlling for comorbidities and IBD severity, corticosteroids (hazard ratio [HR] 5.4; CI 4.6-6.2) and anti-TNFs (HR 1.6; CI 1.3-2.1) were associated with invasive fungal infections. CONCLUSIONS: Invasive fungal infections are more common than TB in patients with IBD. The risk of invasive fungal infections with corticosteroids is more than double that of anti-TNFs. Minimizing corticosteroid use in IBD patients may decrease the risk of fungal infections

Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study

Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism

Mining the Metal-Rich Stars for Planets

We examine the correlation between stellar metallicity and short period planets. It appears that approximately 1% of dwarf stars in the solar neighborhood harbor short-period planets characterized by near-circular orbits and orbital periods P<20 days. However, among the most metal-rich stars (defined as having [Fe/H]>0.2 dex), it appears that the fraction increases to 10%. Using the Hipparcos database and the Hauck & Mermilliod (1998) compilation of Stromgren uvby photometry, we identify a sample of 206 metal-rich stars of spectral type K, G, and F which have an enhanced probability of harboring short-period planets. Many of these stars would be excellent candidates for addition to radial velocity surveys. We have searched the Hipparcos epoch photometry for transiting planets within our 206 star catalog. We find that the quality of the Hipparcos data is not high enough to permit unambiguous transit detections. It is, however, possible to identify candidate transit periods. We then discuss various ramifications of the stellar metallicity - planet connection. First, we show that there is preliminary evidence for increasing metallicity with increasing stellar mass among known planet-bearing stars. This trend can be explained by a scenario in which planet-bearing stars accrete an average of 30 Earth Masses of rocky material after the gaseous protoplanetary disk phase has ended. We present dynamical calculation which suggest that a survey of metallicities of spectroscopic binary stars can be used to understand the root cause of the stellar metallicity - planet connection.Comment: 36 pages, 8 figures, 2 tables, accepted by Astrophysical Journa

Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees

Hepatitis C virus (HCV) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers. Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population. Human monoclonal antibody HCV1 recognizes a highly-conserved linear epitope of the HCV E2 envelope glycoprotein (amino acids 412-423) and neutralizes a broad range of HCV genotypes. In a chimpanzee model, a single dose of 250 mg/kg HCV1 delivered 30 minutes prior to infusion with genotype 1a H77 HCV provided complete protection from HCV infection, whereas a dose of 50 mg/kg HCV1 did not protect. In addition, an acutely-infected chimpanzee given 250 mg/kg HCV1 42 days following exposure to virus had a rapid reduction in viral load to below the limit of detection before rebounding 14 days later. The emergent virus displayed an E2 mutation (N415K/D) conferring resistance to HCV1 neutralization. Finally, three chronically HCV-infected chimpanzees were treated with a single dose of 40 mg/kg HCV1 and viral load was reduced to below the limit of detection for 21 days in one chimpanzee with rebounding virus displaying a resistance mutation (N417S). The other two chimpanzees had 0.5-1.0 log(10) reductions in viral load without evidence of viral resistance to HCV1. In vitro testing using HCV pseudovirus (HCVpp) demonstrated that the sera from the poorly-responding chimpanzees inhibited the ability of HCV1 to neutralize HCVpp. Measurement of antibody responses in the chronically-infected chimpanzees implicated endogenous antibody to E2 and interference with HCV1 neutralization although other factors may also be responsible. These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo