Supermassive Binaries and Extragalactic Jets

Some quasars show Doppler shifted broad emission line peaks. I give new statistics of the occurrence of these peaks and show that, while the most spectacular cases are in quasars with strong radio jets inclined to the line of sight, they are also almost as common in radio-quiet quasars. Theories of the origin of the peaks are reviewed and it is argued that the displaced peaks are most likely produced by the supermassive binary model. The separations of the peaks in the 3C 390.3-type objects are consistent with orientation-dependent "unified models" of quasar activity. If the supermassive binary model is correct, all members of "the jet set" (astrophysical objects showing jets) could be binaries.Comment: 31 pages, PostScript, missing figure is in ApJ 464, L105 (see http://www.aas.org/ApJ/v464n2/5736/5736.html

An Internet-Based Simulation Model for Nitrogen Management in Agricultural Settings

Complex chemical, physical, and biological processes mediate nitrogen (N) transformations and movement during agricultural production, making the optimization of fertilizer use and environmental protection exceedingly difficult. Various computer models have been developed to simulate the site-specific fate and transport of N resulting from different crop production scenarios, but these models are very complex and difficult to use for most farmers, consultants, and conservationists. In an effort to facilitate access and simplify the use of sophisticated models, the U.S. Department of Agriculture (USDA) has developed an Internet-based nitrogen analysis tool. Based on the Nitrate Leaching and Economic Analysis Package (NLEAP), the Web site allows a user to conduct multiyear N simulation modeling specific to a crop field. Servers handle much of the required data assembly and formatting, thus sparing the user�s resources. Model runs are executed on the servers and the results are transmitted to the user. This new tool is presented along with early implementation results

A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced Drug Reaction with Eosinophilia and systemic symptoms

Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. We recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Identification of individuals with the risk allele prior to or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, improve drug safety and antibiotic treatment options. A prerequisite to the success of a pharmacogenetic screening tests is the development of simple, robust, cost-effective single HLA allele test that can be implemented in routine diagnostic laboratories. In this study, we developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including thirty HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared to ASHI accredited sequence-based high-resolution, full allelic HLA typing, this assay demonstrates 100% accuracy, sensitivity of 100% (95% CI: 88.43% to 100%) and specificity of 100% (95% CI: 99.14% to 100%). The lowest limit of detection of this assay using the Power Up SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate HLA-A*32:01 allele from closely related non-HLA-A*32 alleles and may be used in clinical settings to identify individuals with the risk allele prior or during the course of vancomycin therapy

Influence of human leukocyte antigen (HLA) alleles and killer cell immunoglobulin-like receptors (KIR) types on heparin-induced thrombocytopenia (HIT)

Objectives Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT.\ud Methods HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina® OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. P values for HLA and KIR association were corrected using a false discovery rate (FDR) q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Results Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81[1.57-5.02], p=2.1x10-4, q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). Conclusions The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Background Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs. Objective To determine if variation in the HLA region is associated with vancomycin-induced DRESS. Methods Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt’s deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele. Results Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10-8) and 6.3% of the BioVU population (n=54,249) (p=2x10-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks. Conclusions HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics

Discovery of a novel inner membrane-associated bacterial structure related to the flagellar type III secretion system

Microbial Biotechnolog

Broadband Quantum Enhancement of the LIGO Detectors with Frequency-Dependent Squeezing

Quantum noise imposes a fundamental limitation on the sensitivity of interferometric gravitational-wave detectors like LIGO, manifesting as shot noise and quantum radiation pressure noise. Here, we present the first realization of frequency-dependent squeezing in full-scale gravitational-wave detectors, resulting in the reduction of both shot noise and quantum radiation pressure noise, with broadband detector enhancement from tens of hertz to several kilohertz. In the LIGO Hanford detector, squeezing reduced the detector noise amplitude by a factor of 1.6 (4.0 dB) near 1 kHz; in the Livingston detector, the noise reduction was a factor of 1.9 (5.8 dB). These improvements directly impact LIGO's scientific output for high-frequency sources (e.g., binary neutron star postmerger physics). The improved low-frequency sensitivity, which boosted the detector range by 15%-18% with respect to no squeezing, corresponds to an increase in the astrophysical detection rate of up to 65%. Frequency-dependent squeezing was enabled by the addition of a 300-meter-long filter cavity to each detector as part of the LIGO A+ upgrade