A Low Noise Thermometer Readout for Ruthenium Oxide Resistors

The thermometer and thermal control system, for the Absolute Radiometer for Cosmology, Astrophysics, and Diffuse Emission (ARCADE) experiment, is described, including the design, testing, and results from the first flight of ARCADE. The noise is equivalent to about 1 Omega or 0.15 mK in a second for the RuO_2 resistive thermometers at 2.7 K. The average power dissipation in each thermometer is 1 nW. The control system can take full advantage of the thermometers to maintain stable temperatures. Systematic effects are still under investigation, but the measured precision and accuracy are sufficient to allow measurement of the cosmic background spectrum. Journal-ref: Review of Scientific Instruments Vol 73 #10 (Oct 2002)Comment: 5 pages text 7 figure

The Temperature of the CMB at 10 GHz

We report the results of an effort to measure the low frequency portion of the spectrum of the Cosmic Microwave Background Radiation (CMB), using a balloon-borne instrument called ARCADE (Absolute Radiometer for Cosmology, Astrophysics, and Diffuse Emission). These measurements are to search for deviations from a thermal spectrum that are expected to exist in the CMB due to various processes in the early universe. The radiometric temperature was measured at 10 and 30 GHz using a cryogenic open-aperture instrument with no emissive windows. An external blackbody calibrator provides an in situ reference. A linear model is used to compare the radiometer output to a set of thermometers on the instrument. The unmodeled residuals are less than 50 mK peak-to-peak with a weighted RMS of 6 mK. Small corrections are made for the residual emission from the flight train, atmosphere, and foreground Galactic emission. The measured radiometric temperature of the CMB is 2.721 +/- 0.010 K at 10 GHz and 2.694 +/- 0.032 K at 30 GHz.Comment: 8 pages including 5 figures. Submitted to The Astrophysical Journa

Time-Resolved Transcriptome Analysis of Bacillus subtilis Responding to Valine, Glutamate, and Glutamine

Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector

Learners in a Changing Learning Landscape: Reflections from an Instructional Design Perspective

Van Merriënboer, J. J. G., & Stoyanov, S. (2008). Learners in a changing learning landscape: Reflections from an instructional design perspective. In J. Visser & M. Visser-Valfrey (Eds.), Learners in a changing learning landscape: Reflections from a dialogue on new roles and expectations (pp. 69-90). Dordrecht, The Netherlands: Springer.Both learners and teachers find themselves in a learning landscape that is rapidly changing, along with fast societal and technological developments. This paper discusses the new learning landscape from an instructional design perspective. First, with regard to what is learned, people more than ever need flexible problem-solving and reasoning skills allowing them to deal with new, unfamiliar problem situations in their professional and everyday life. Second, with regard to the context in which learning takes place, learning in technology-rich, informal and professional 24/7 settings is becoming general practice. And third, with regard to the learners themselves, they can more often be characterized as lifelong learners who are mature, bring relevant prior knowledge, and have very heterogeneous expectations and perceptions of learning. High-quality instructional design research should focus on the question which instructional methods and media-method combinations are effective, efficient and appealing in this new learning landscape. Some innovative instructional methods that meet this requirement are discussed

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al

Sub-Kelvin cooling for two kilopixel bolometer arrays in the PIPER receiver

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne telescope mission to search for inflationary gravitational waves from the early universe. PIPER employs two 32 × 40 arrays of superconducting transition-edge sensors, which operate at 100 mK. An open bucket Dewar of liquid helium maintains the receiver and telescope optics at 1.7 K. We describe the thermal design of the receiver and sub-Kelvin cooling with a continuous adiabatic demagnetization refrigerator (CADR). The CADR operates between 70 and 130 mK and provides ≈10 μW cooling power at 100 mK, nearly five times the loading of the two detector assemblies. We describe electronics and software to robustly control the CADR, overall CADR performance in flightlike integrated receiver testing, and practical considerations for implementation in the balloon float environment

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery