27 research outputs found
Microwave multiplexing on the Keck Array
We describe an on-sky demonstration of a microwave-multiplexing readout
system in one of the receivers of the Keck Array, a polarimetry experiment
observing the cosmic microwave background at the South Pole. During the austral
summer of 2018-2019, we replaced the time-division multiplexing readout system
with microwave-multiplexing components including superconducting microwave
resonators coupled to radio-frequency superconducting quantum interference
devices at the sub-Kelvin focal plane, coaxial-cable plumbing and amplification
between room temperature and the cold stages, and a SLAC Microresonator Radio
Frequency system for the warm electronics. In the range 5-6 GHz, a single
coaxial cable reads out 528 channels. The readout system is coupled to
transition-edge sensors, which are in turn coupled to 150-GHz slot-dipole
phased-array antennas. Observations began in April 2019, and we report here on
an initial characterization of the system performance.Comment: 9 pages, 11 figures, Accepted by the Journal of Low Temperature
Physics (Proceedings of the 18th International Workshop on Low Temperature
Detectors
Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis
Selecting RF Amplifiers for Impedance Controlled LLRF Systems - Nonlinear Effects and System Implications
Several high-current accelerators use feedback techniques in the accelerating RF systems to control the impedances seen by the circulating beam. [1, 2] These Direct and Comb Loop architectures put the high power klystron and LLRF signal processing components inside feedback loops, and the ultimate behavior of the systems depends on the individual sub-component properties. Imperfections and non-idealities in the signal processing leads to reduced effectiveness in the impedance controlled loops. In the PEP-II LLRF systems non-linear effects have been shown to reduce the achievable beam currents, increase low-mode longitudinal growth rates and reduce the margins and stability of the LLRF control loops. We present measurements of the driver amplifiers used in the PEP-II systems, and present measurement techniques needed to quantify the small-signal gain, linearity, transient response and image frequency generation of these amplifiers
STRIPLINE TRANSVERSAL FILTER TECHNIQUES FOR SUB-PICOSECOND BUNCH TIMING MEASUREMENTS ∗
Measurement of time of arrival of a particle bunch is a fundamental beam diagnostic. The PEP-II/ALS/BESSY/PLS longitudinal feedback systems use a planar stripline circuit to convert a 30 ps beam BPM impulse signal into a 4 cycle tone burst at the 6th harmonic of the accelerator RF frequency (2.856 GHz). A phase-detection technique is used to measure the arrival time of these BPM impulses with 200 fs rms single-shot resolution (out of a 330 ps dynamic range). Scaled in frequency, this approach is directly applicable to FEL and other subps regime pulse and timing measurements. The transversal circuit structure is applicable to measurement of microbunches or closely spaced bunches (the PEP-II/ALS/BESSY/PLS examples make independent measurements at 2 ns bunch spacing) and opens up some new diagnostic and control possibilities. This paper reviews the principles of the technique, and uses data from PEP-II operations to predict the limits of performance of this measurement scheme for arrival phase measurement. These predictions are compared with results in the literature from electro-optic sub-picosecond beam timing and phasing diagnostics
Attenuation of acute lung injury in transgenic mice expressing human transforming growth factor-α
Per rectal portal scintigraphy in the diagnosis and management of feline congenital portosystemic shunts
Use of Transition Models to Design High Performance TESs for the LCLS-II Soft X-Ray Spectrometer
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Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma.
BackgroundGene-modified autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1-specific HLA-A*02-restricted peptide SLLMWITQC (NY-ESO-1 SPEAR T-cells; GSK 794), have demonstrated clinical activity in patients with advanced synovial sarcoma (SS). The factors contributing to gene-modified T-cell expansion and the changes within the tumor microenvironment (TME) following T-cell infusion remain unclear. These studies address the immunological mechanisms of response and resistance in patients with SS treated with NY-ESO-1 SPEAR T-cells.MethodsFour cohorts were included to evaluate antigen expression and preconditioning on efficacy. Clinical responses were assessed by RECIST v1.1. Engineered T-cell persistence was determined by qPCR. Serum cytokines were evaluated by immunoassay. Transcriptomic analyses and immunohistochemistry were performed on tumor biopsies from patients before and after T-cell infusion. Gene-modified T-cells were detected within the TME via an RNAish assay.ResultsResponses across cohorts were affected by preconditioning and intra-tumoral NY-ESO-1 expression. Of the 42 patients reported (data cut-off 4June2018), 1 patient had a complete response, 14 patients had partial responses, 24 patients had stable disease, and 3 patients had progressive disease. The magnitude of gene-modified T-cell expansion shortly after infusion was associated with response in patients with high intra-tumoral NY-ESO-1 expression. Patients receiving a fludarabine-containing conditioning regimen experienced increases in serum IL-7 and IL-15. Prior to infusion, the TME exhibited minimal leukocyte infiltration; CD163+ tumor-associated macrophages (TAMs) were the dominant population. Modest increases in intra-tumoral leukocytes (≤5%) were observed in a subset of subjects at approximately 8 weeks. Beyond 8 weeks post infusion, the TME was minimally infiltrated with a TAM-dominant leukocyte infiltrate. Tumor-associated antigens and antigen presentation did not significantly change within the tumor post-T-cell infusion. Finally, NY-ESO-1 SPEAR T cells trafficked to the TME and maintained cytotoxicity in a subset of patients.ConclusionsOur studies elucidate some factors that underpin response and resistance to NY-ESO-1 SPEAR T-cell therapy. From these data, we conclude that a lymphodepletion regimen containing high doses of fludarabine and cyclophosphamide is necessary for SPEAR T-cell persistence and efficacy. Furthermore, these data demonstrate that non-T-cell inflamed tumors, which are resistant to PD-1/PD-L1 inhibitors, can be treated with adoptive T-cell based immunotherapy.Trial registrationClinicalTrials.gov, NCT01343043 , Registered 27 April 2011