Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Design and Field-of-View Calibration of 114-660-GHz Optics of the Earth Observing System Microwave Limb Sounder

This paper describes the optics design and field-of view (FOV) calibration for five radiometers covering 114-660 GHz which share a common antenna in the Microwave Limb Sounder instrument on the National Aeronautics and Space Administration's Aura satellite. Details of near-field pattern measurements are presented. Estimated systematic scaling uncertainties (3/spl sigma/) on calibrated limb emissions, due to FOV calibration uncertainties, are below 0.4%. 3/spl sigma/ uncertainties in beamwidth and relative pointing of radiometer boresights are 0.006A(deg) and 0.003A(deg) , respectively. The uncertainty in modeled instrument response, due to the scan dependence of FOV patterns, is less than +/- 0.24 K equivalent blackbody temperature. Refinements to the calibration using in-flight data are presented

On Orbit Commissioning of the Earth Observing System Microwave Limb Sounder (EOS MLS) On the Aura Spacecraft

The Microwave Limb Sounder instrument was launched aboard NASA's EOS AURA satellite in July, 2004. The overall scientific objectives for MLS are to measure temperature, pressure, and several important chemical species in the upper troposphere and stratosphere relevant to ozone processes and climate change. MLS consists of a suite of radiometers designed to operate from 11 8 GHz to 2.5 THz, with two antennas (one for 2.5 THz, the other for the lower frequencies) that scan vertically through the atmospheric limb, and spectrometers with spectral resolution of 6 MHz at spectral line centers. This paper describes the on-orbit commissioning the MLS instrument which includes activation and engineering functional verifications and calibrations

The Earth Observing System Microwave Limb Sounder (EOS MLS) on the Aura Satellite

The Earth Observing System Microwave Limb Sounder measures several atmospheric chemical species (OH, HO2, H2O, O3, HCl, ClO, HOCl, BrO, HNO3, N2O, CO, HCN, CH3CN, volcanic SO2), cloud ice, temperature, and geopotential height to improve our understanding of stratospheric ozone chemistry, the interaction of composition and climate, and pollution in the upper troposphere. All measurements are made simultaneously and continuously, during both day and night. The instrument uses heterodyne radiometers that observe thermal emission from the atmospheric limb in broad spectral regions centered near 118, 190, 240, and 640 GHz, and 2.5 THz. It was launched July 15, 2004 on the National Aeronautics and Space Administration's Aura satellite and started full-up science operations on August 13, 2004. An atmospheric limb scan and radiometric calibration for all bands are performed routinely every 25 s. Vertical profiles are retrieved every 165 km along the suborbital track, covering 82 S to 82 N latitudes on each orbit. Instrument performance to date has been excellent; data have been made publicly available; and initial science results have been obtained

Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity.

Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g., IFNα→p-STAT5 in B cells) in peripheral blood mononuclear cells (PBMC) from 194 patients with longstanding RA (including 98 patients before and after treatment), and 41 healthy controls (HC). We found multiple differences between patients with RA compared to HC, predominantly in cytokine-induced Jak/STAT signaling in many immune cell subsets, suggesting pathways that may be associated with susceptibility to RA. We also found that high RA disease activity, compared to low disease activity, was associated with decreased (e.g., IFNα→p-STAT5, IL-10→p-STAT1) or increased (e.g., IL-6→STAT3) response to stimuli in multiple cell subsets. Finally, we compared signaling in patients with established, refractory RA before and six months after initiation of methotrexate (MTX) or TNF inhibitors (TNFi). We noted significant changes from pre-treatment to post-treatment in IFNα→p-STAT5 signaling and IL-10→p-STAT1 signaling in multiple cell subsets; these changes brought the aberrant RA signaling profiles toward those of HC. This large, comprehensive functional signaling pathway study provides novel insights into the pathogenesis of RA and shows the potential of quantification of cytokine-induced signaling as a biomarker of disease activity or treatment response